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Background: Osseointegrated dental implants are widely established as a first-choice treatment for the replacement of missing teeth. Clinical outcomes are however often compromised by short or longer-term biological complications and pathologies. Nanoparticle-coated materials represent a very active research area with the potential to enhance clinical outcomes and reduce complications of implant therapy. This scoping review aimed to summarize current research on various types of nanoparticles (NPs) used as surface modifiers of dental implants and their potential to promote biological and clinical outcomes. Methods: A systematic electronic search was conducted in SCOPUS, PubMed and Google Scholar aiming to identify in vivo, in situ, or in vitro studies published between 2014 and 2024. Inclusion and exclusion criteria were determined and were described in the methods section. Results: A total of 169 articles (44 original papers from Scopus and PubMed, and 125 articles from Google Scholar) were identified by the electronic search. Finally, 30 studies fit the inclusion criteria and were further used in this review. The findings from the selected papers suggest that nanoparticle-coated dental implants show promising results in enhancing bone regeneration and promoting angiogenesis around the implant site. These effects are due to the unique physicochemical properties of nanoparticle-coated implants and the controlled release of bioactive molecules from nanoparticle-modified surfaces. Conclusion: Nanoscale modifications displayed unique properties which could significantly enhance the properties of dental implants and further accelerate revascularization, and osseointegration while facilitating early implant loading. Yet, since many of these findings were based on in-vitro/in-situ systems, further research is required before such technology reaches clinical application. [ABSTRACT FROM AUTHOR]

Background: Spinal cord compression is a pathology seen in routine clinical practice. However, there remain a number of unanswered questions around both the understanding of the pathogenesis and the best method of treatment of the condition. This is partly due to the issues of the real-life testing of the physical properties of the spinal cord, either through the use of cadaveric human specimens or through animal testing, both of which have methodological, as well as ethical, issues. Design and methods: This paper details a protocol for a systematic review of the literature on the mechanical properties of the spinal cord. We will conduct a literature search of a number of electronic databases, along with the grey literature, as a single-stage search. All literature will be screened for appropriate studies which will then be reviewed fully to extract relevant information on the methodology and mechanics of the reported testing along with the results. Two reviewers will separately screen and extract the data, with a comparison of results to ensure concordance. Conflicts will be resolved through discussion and independent arbitration as required. The methodological quality of the studies will be assessed within the ARRIVE guidelines using the CAMARADES framework and SYRCLE risk of bias tool. A narrative synthesis will be created with the appropriate tables to describe the demographics and findings of the included studies. Discussion: The systematic review described here will form the basis of an understanding of the current literature around the physical properties of the spinal cord. This will allow future work to develop a physical model of the spinal cord, which is translatable to patients for analysis and testing in a controlled and repeatable fashion. Such a model would be the basis for further clinical research to improve outcomes from this condition. Trial registration: Prospero registration number: CRD42022361933. [ABSTRACT FROM AUTHOR]

Background: Dauricine (DAU), a benzyl tetrahydroisoquinoline alkaloid isolated from the root of Menispermum dauricum DC, exhibits promising anti-Alzheimer's disease (AD) effects, but its underlying mechanisms remain inadequately investigated. This paper aims to identify potential targets and molecular mechanisms of DAU in AD treatment. Methods: Network pharmacology and molecular docking simulation method were used to screen and focus core targets. Various transgenic Caenorhabditis elegans models were chosen to validate the anti-AD efficacy and mechanism of DAU. Results: There are 66 potential DAU-AD target intersections identified from 100 DAU and 3036 AD-related targets. Subsequent protein-protein interaction (PPI) network analysis identified 16 core targets of DAU for anti-AD. PIK3CA, AKT1 and mTOR were predicted to be the central targets with the best connectivity through the analysis of "compound-target-biological process-pathway network". Molecular docking revealed strong binding affinities between DAU and PIK3CA, AKT1, and mTOR. In vivo experiments demonstrated that DAU effectively reduced paralysis in AD nematodes caused by Aβ aggregation toxicity, downregulated expression of PIK3CA, AKT1, and mTOR homologues (age-1, akt-1, let-363), and upregulated expression of autophagy genes and the marker protein LGG-1. Simultaneously, DAU increased lysosomal content and enhanced degradation of the autophagy-related substrate protein P62. Thioflavin T（Th-T）staining experiment revealed that DAU decreased Aβ accumulation in AD nematodes. Further experiments also confirmed DAU's protein scavenging activity in polyglutamine (polyQ) aggregation nematodes. Conclusion: Collectively, the mechanism of DAU against AD may be related to the activation of the autophagy-lysosomal protein clearance pathway, which contributes to the decrease of Aβ aggregation and the restoration of protein homeostasis. [ABSTRACT FROM AUTHOR]

Purpose: Studies have recently shown a correlation between the elemental components of coal dusts, including potassium aluminosilicates, and the lung response as a potential driver for lung diseases associated with inhalation of coal dust. Here we aimed to systematically review the evidence for the association between exposure to potassium bearing dusts and lung outcomes in human studies as well as adverse cellular response in animal/cell culture studies. Methods: A systematic search of the National Library of Medicine (PubMed), Embase and Web of Science was conducted in May 2024. Studies regarding exposure to potassium bearing dusts and aluminosilicates and respiratory consequence were included in the search. Articles were screened, with a secondary assessment for relevance and extraction of key information using a systematic review process. Results: We identified 64 studies, of which 35 were human studies, 22 involved animal experiments and 12 were in vitro studies with 5 papers having both in vivo and in vitro studies. Our review found some evidence that a range of potassium rich dusts increased incidence of respiratory symptoms and lung diseases, although the effect on radiological changes in the lung and pulmonary function loss was not consistent. The in vivo animal and in vitro studies consistently demonstrated an inflammatory response and cytotoxic effect after exposure to these dusts. Conclusion: Given complexity in the dust compositions and lack of direct evidence attributing these specific responses to potassium, we are not able to conclude the effect of potassium minerals in coal on development of respiratory diseases, warranting further research. [ABSTRACT FROM AUTHOR]

Background: This study aims to investigate the influence of different dentin pretreatment procedures on the resulting abrasive dentin wear. Methods: Two groups (A, B) of 60 dentin samples each were prepared. Group A was brushed with an abrasive slurry (RDA = 85) and group B with a different abrasive slurry (RDA = 174). Four subgroups in each group (n = 15) were created (A1–A4) and (B1–B4). The subgroups were pretreated as follows: A1 + B1 with 1200-grit grinding paper, A2 + B2 with 1200- and 2000-grit papers, A3 + B3 with 1200-, 2000-, and 4000-grit papers, A4 + B4 with 1200-, 2000-, 4000-grit papers and with 1000 brushing strokes with a slurry of Elmex toothpaste. All samples were brushed for 25 min at 120 strokes/min. Abrasive dentin wear was measured for each sample profilometrically and the subgroups were compared with each other within the same group. Repeated measures one-way ANOVA was conducted to compare the subgroups and pairwise contrasts were estimated for multiple testing according to Tukey (α = 0.05). Results: The resulting abrasive dentin wear in group A ranged between 15.3 ± 3.4 µm and 17.3 ± 5.5 µm and between 20.3 ± 6.8 µm and 22.5 ± 2.6 µm in group B. No statistically significant difference was noticed between any subgroups within the same group (p ˃ 0.05). Conclusions: Different dentin pretreatment procedures do not affect the resulting abrasive dentin wear independent of the RDA value of the employed abrasive slurry. [ABSTRACT FROM AUTHOR]

Background: Depression is a mental disorder characterized by a pervasive low mood and loss of pleasure or interest in usual activities, and often results in cognitive dysfunction. The disturbance of cognitive processes associated with depression, especially the impairment of learning and memory, exacerbates illness and increases recurrence of depression. XingPiJieYu (XPJY) is one of the most widely clinical formulas of traditional Chinese medicine (TCM) and can improve the symptoms of depression, including learning and memory. However, its regulatory effects haven't been comprehensively studied so far. Recently, some animal tests have indicated that the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA)-cAMP response element-binding protein (CREB)-brain derived neurotrophic factor (BDNF) signaling pathway in hippocampus is closely related to depression and the pathogenesis of cognitive function impairments. The present study was performed to investigate the effect and mechanism of XPJY on depression and learning and memory in animal model. Materials: The rat model of depression was established by chronic unpredictable stress (CUS) for 21 days. The rats were randomly divided into six groups: control group, CUS group, CUS + XPJY (1.4 g/kg, 0.7 g/kg and 0.35 g/kg) groups, and CUS + sertraline (10 mg/kg) group. The sucrose preference, open field exploration and Morris water maze (MWM) were tested. The expression of cAMP, CREB, PKA and BDNF protein in hippocampus was examined with Elisa and Western Blot. The mRNA level of CREB and BDNF in hippocampus was measured with PCR. Results: The results demonstrated that rats subjected to CUS exhibited decreases in sucrose preference, total ambulation, percentage of central ambulation, rearing in the open field test and spatial performance in the MWM. CUS reduced the expression of cAMP, PKA, CREB and BDNF in hippocampus of model rats. These effects could be reversed by XPJY. Conclusion: The results indicated that XPJY can improve depression and related learning and memory and the effect of XPJY is partly exerted through the cAMP-PKA-CREB-BDNF signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Excessive inflammation is a major cause of implant failure. The surface morphology, hydrophilicity, and loading of biomaterials are major properties modulating anti-inflammatory macrophage activation. This paper investigates the regulatory effects of modifying the surface of Titanium dioxide nanotubes (TNTs) with graphene oxide (GO) on the polarization of mouse monocyte macrophages (RAW264.7). Methods: TNT was produced by the anodic oxidation of titanium. GO was subsequently electrodeposited on the TNT to obtain a TNT–GO composite. The samples were characterised through scanning electron microscopy (SEM), Raman spectroscopy, and X-ray diffraction. RAW264.7 cells were separately seeded onto the surface of three groups of samples: pure Ti, TNT, and TNT–GO. Under the condition of lipopolysaccharide stimulation, the influence of the sample surfaces on the gene expression profiles was investigated through RNA sequence analysis. In addition, cell spreading was observed through SEM, cell adhesion and proliferation were analysed using the CCK8 assay, and the expression of inflammation-related factors was investigated by ELISA and cellular immunofluorescence staining. The production of reactive oxygen species (ROS) in the RAW264.7 cells on the surface of the three groups was detected via immunofluorescence staining. Results: The CCK8 results indicated that the adhesion and proliferation of the RAW264.7 cells were reduced on the TNT and TNT–GO surfaces. ELISA results revealed significant differences in the pro-inflammatory factors tumour necrosis factor-α and interleukin-6 secretion among the three groups at 24 h (p < 0.05). The secretion of pro-inflammatory factors significantly reduced and the expression of anti-inflammatory factor IL-10 increased on the TNT and TNT–GO surfaces. The RNA sequencing, ELISA, and cell immunofluorescence staining test results suggested that the inflammatory response of M1 polarization was reduced and the M2 polarization of macrophages was induced on the TNT–GO surface, which may be attributed to the reduction in ROS production. Conclusions: Under lipopolysaccharide stimulation, the inflammatory response of the RAW264.7 cells was reduced and the M2 polarization of macrophages was promoted on the TNT–GO surface, which may be caused by the reduced ROS production. Consequently, the designed TNT–GO material is promising for implants owing to its excellent inflammation regulation ability. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) is a major cause of heart failure. The carboxypeptidase cathepsin A is a novel target in the treatment of cardiac failure. We aim to show that recently developed inhibitors of the protease cathepsin A attenuate post-MI heart failure.Methods: Mice were subjected to permanent left anterior descending artery (LAD) ligation or sham operation. 24 h post-surgery, LAD-ligated animals were treated with daily doses of the cathepsin A inhibitor SAR1 or placebo. After 4 weeks, the three groups (sham, MI-placebo, MI-SAR1) were evaluated.Results: Compared to sham-operated animals, placebo-treated mice showed significantly impaired cardiac function and increased plasma BNP levels. Cathepsin A inhibition prevented the increase of plasma BNP levels and displayed a trend towards improved cardiac functionality. Proteomic profiling was performed for the three groups (sham, MI-placebo, MI-SAR1). More than 100 proteins were significantly altered in placebo-treated LAD ligation compared to the sham operation, including known markers of cardiac failure as well as extracellular/matricellular proteins. This ensemble constitutes a proteome fingerprint of myocardial infarction induced by LAD ligation in mice. Cathepsin A inhibitor treatment normalized the marked increase of the muscle stress marker CA3 as well as of Igγ 2b and fatty acid synthase. For numerous further proteins, cathepsin A inhibition partially dampened the LAD ligation-induced proteome alterations.Conclusions: Our proteomic and functional data suggest that cathepsin A inhibition has cardioprotective properties and support a beneficial effect of cathepsin A inhibition in the treatment of heart failure after myocardial infarction. [ABSTRACT FROM AUTHOR]

Temporal accuracy is a fundamental characteristic of logging technology and is needed to correlate data streams. Single biologgers sensing animal movement (accelerometers, gyroscope, magnetometers, collectively inertial measurement unit; IMU) have been extensively used to study the ecology of animals. To better capture whole body movement and increase the accuracy of behavior classification, there is a need to deploy multiple loggers on a single individual to capture the movement of multiple body parts. Yet due to temporal drift, accurately aligning multiple IMU datasets can be problematic, especially as deployment duration increases. In this paper we quantify temporal drift and errors in commercially available IMU data loggers using a combination of robotic and animal borne experiments. The variance in drift rate within a tag is over an order of magnitude lower (σ = 0.001 s h−1) than the variance between tags (σ = 0.015 s·h−1), showing that recording frequency is a characteristic of each tag and not a random variable. Furthermore, we observed a large offset (0.54 ± 0.016 s·h−1) between two groups of tags that had differing recording frequencies, and we observed three instances of instantaneous temporal jumps within datasets introducing errors into the data streams. Finally, we show that relative drift rates can be estimated even when deployed on animals displaying various behaviors without the tags needing to be simultaneously moved. For the tags used in this study, drift rates can vary significantly between tags, are repeatable, and can be accurately measured in the field. The temporal alignment of multiple tag datasets allows researchers to deploy multiple tags on an individual animal which will greatly increase our knowledge of movement kinematics and expand the range of movement characteristics that can be used for behavioral classification. [ABSTRACT FROM AUTHOR]

Paradoxically, tumor development and progression can be inhibited and promoted by the immune system. After three stages of immune editing, namely, elimination, homeostasis and escape, tumor cells are no longer restricted by immune surveillance and thus develop into clinical tumors. The mechanisms of immune escape include abnormalities in antitumor-associated immune cells, selection for immune resistance to tumor cells, impaired transport of T cells, and the formation of an immunosuppressive tumor microenvironment. A population of distinct immature myeloid cells, myeloid-derived suppressor cells (MDSCs), mediate immune escape primarily by exerting immunosuppressive effects and participating in the constitution of an immunosuppressive microtumor environment. Clinical trials have found that the levels of MDSCs in the peripheral blood of cancer patients are strongly correlated with tumor stage, metastasis and prognosis. Moreover, animal experiments have confirmed that elimination of MDSCs inhibits tumor growth and metastasis to some extent. Therefore, MDSCs may become the target of immunotherapy for many cancers, and eliminating MDSCs can help improve the response rate to cancer treatment and patient survival. However, a clear definition of MDSCs and the specific mechanism involved in immune escape are lacking. In this paper, we review the role of the MDSCs population in tumor development and the mechanisms involved in immune escape in different tumor contexts. In addition, we discuss the use of these cells as targets for tumor immunotherapy. This review not only contributes to a systematic and comprehensive understanding of the essential role of MDSCs in immune system reactions against tumors but also provides information to guide the development of cancer therapies targeting MDSCs. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluates the effectiveness of a combined regimen involving injectable hydrogels for the treatment of experimental myocardial infarction. Patient concerns: Myocardial infarction is an acute illness that negatively affects quality of life and increases mortality rates. Experimental models of myocardial infarction can aid in disease research by allowing for the development of therapies that effectively manage disease progression and promote tissue repair. Diagnosis: Experimental animal models of myocardial infarction were established using the ligation method on the anterior descending branch of the left coronary artery (LAD). Interventions: The efficacy of intracardiac injection of hydrogels, combined with cells, drugs, cytokines, extracellular vesicles, or nucleic acid therapies, was evaluated to assess the functional and morphological improvements in the post-infarction heart achieved through the combined hydrogel regimen. Outcomes: A literature review was conducted using PubMed, Web of Science, Scopus, and Cochrane databases. A total of 83 papers, including studies on 1332 experimental animals (rats, mice, rabbits, sheep, and pigs), were included in the meta-analysis based on the inclusion and exclusion criteria. The overall effect size observed in the group receiving combined hydrogel therapy, compared to the group receiving hydrogel treatment alone, resulted in an ejection fraction (EF) improvement of 8.87% [95% confidence interval (CI): 7.53, 10.21] and a fractional shortening (FS) improvement of 6.31% [95% CI: 5.94, 6.67] in rat models, while in mice models, the improvements were 16.45% [95% CI: 11.29, 21.61] for EF and 5.68% [95% CI: 5.15, 6.22] for FS. The most significant improvements in EF (rats: MD = 9.63% [95% CI: 4.02, 15.23]; mice: MD = 23.93% [95% CI: 17.52, 30.84]) and FS (rats: MD = 8.55% [95% CI: 2.54, 14.56]; mice: MD = 5.68% [95% CI: 5.15, 6.22]) were observed when extracellular vesicle therapy was used. Although there have been significant results in large animal experiments, the number of studies conducted in this area is limited. Conclusion: The present study demonstrates that combining hydrogel with other therapies effectively improves heart function and morphology. Further preclinical research using large animal models is necessary for additional study and validation. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA), characterized by inflammation and articular cartilage degradation, is a prevalent arthritis among geriatric population. This paper was to scrutinize the novel mechanism of long noncoding RNA (lncRNA) NEAT1 in OA etiology. Methods: A total of 10 OA patients and 10 normal individuals was included in this study. Cell model of OA was built in human normal chondrocytes induced by lipopolysaccharide (LPS). An OA Wistar rat model was established through intra-articular injection of L-cysteine and papain mixtures (proportion at 1:2) into the right knee. Quantitative reverse transcription-polymerase chain reaction was employed to ascertain the expression levels of NEAT1, microRNA (miR)-374b-5p and post-GPI attachment to protein 1 (PGAP1), while dual-luciferase reporter experiments were used for the validation of target relationship among them. Cell cycle and apoptosis were calculated by flow cytometry analysis. CCK-8 assay was done to evaluate the proliferative potentials of chondrocytes. The levels of cell cycle-related proteins (Cyclin A1, Cyclin B1 and Cyclin D2) and pro-apoptotic proteins (Caspase3 and Caspase9) were measured by western blotting. Tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 levels were determined via ELISA. Hematoxylin & eosin (HE) Staining was used for pathological examination in OA rats. Results: Pronounced downregulation of NEAT1 and PGAP1 and high amounts of miR-374b-5p were identified in OA patients, LPS-induced chondrocytes and OA rats. NEAT1 targeted miR-374b-5p to control PGAP1 expression. Loss of NEAT1 or upregulation of miR-374b-5p dramatically accelerated apoptosis, led to the G1/S arrest and promoted the secretion of inflammatory cytokines in LPS-induced chondrocytes, while ectopic expression of PGAP1 exhibited the opposite influences on chondrocytes. Additionally, we further indicated that upregulation of miR-374b-5p attenuated the effects of PGAP1 overexpression on LPS-induced chondrocytes. Conclusions: Reduced NEAT1 induces the development of OA via miR-374b-5p/PGAP1 pathway. This suggests that the regulatory axis NEAT1/miR-374b-5p/PGAP1 is a novel and prospective target for OA treatment. [ABSTRACT FROM AUTHOR]

Background: Sepsis poses a serious threat to human life and health, with limited options for current clinical treatments. Acupuncture plays an active role in treating sepsis. However, previous studies have focused on the neuromodulatory effect of acupuncture, neglecting its network modulatory effect. Exosomes, as a new way of intercellular communication, may play an important role in transmitting acupuncture information. This paper explores the possibility of electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs as a potential treatment for sepsis. Methods: The sepsis mouse model was established by intraperitoneal injection of lipopolysaccharide (LPS) (12 mg/kg, 24 mg/kg), and EA (continuous wave, 10 Hz, intensity 5) or intraperitoneal injection of Acupuncture Exosomes (Acu-exo) were performed before the model establishment. The therapeutic effect was evaluated by survival rate, ELISA, H&E staining and lung wet/dry weight ration (W/D). In vivo imaging of small animals was used to observe the accumulation of Acu-exo in various organs of sepsis mice. LPS was used to induce macrophages in cell experiments, and the effect of Acu-exo on macrophage inflammatory cytokines was observed. In addition, The miRNA sequencing method was further used to detect the serum exosomes of normal and EA-treated mice, and combined with network biology analysis methods to screen possible key targets. Results: EA and Acu-exo reduced the W/D and lung tissue damage in sepsis mice, down-regulated the expression of serum inflammatory cytokines TNF-α and IL-6, and increased the survival rate of sepsis mice. In vivo imaging of small animals found that Acu-exo were accumulated in the lungs of sepsis mice. Cell experiments proved that Acu-exo down-regulated the expression of inflammatory cytokines TNF-α, IL-6 and IL-1β to alleviate the inflammatory response induced by LPS in macrophages. MiRNA sequencing revealed 53 differentially expressed miRNAs, and network biology analysis revealed the key targets of Acu-exo in sepsis treatment. Conclusion: Electroacupuncture-driven endogenous circulating serum exosomes and their carried miRNAs may be a potential treatment for sepsis. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common age-related joint disease, characterized by chronic inflammation, progressive articular cartilage destruction and subchondral osteosclerosis. More and more evidence showed that microRNAs (miRNAs) play a key role in various diseases, but the specific mechanism of miRNAs in OA is not clear. The purpose of this study was to investigate the expression level and role of miR-181a-5p in OA and its related mechanism. Here we identified the key gene DEAD-box RNA helicase 3X (DDX3X) in the OA dataset by bioinformatics analysis. At the same time, miRNAs targeting DDX3X were screened, and miR-181a-5p was selected as the next research object. Then we used different concentrations of interleukin-1 beta (IL-1β)-induced in vitro model of arthritis, and found that IL-1β can stimulate cells to release nitric oxide. The expression levels of miR-181a-5p and DDX3X in mouse chondrocyte cell line ATDC5 induced by IL-1β at a concentration of 10ug/mL were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). IL-1β induced a decrease in the expression of miR-181a-5p and an increase in the expression of DDX3X in ATDC5 cells. mimic miR-181a-5p or inhibitor miR-181a-5p were transfected into ATDC5 cells, and the levels of inflammatory mediators in the cells were detected by enzyme-linked immunosorbent assay, and the results showed that miR-181a-5p could reduce the release of tumor necrosis factor-α, IL-1β, IL-6 and inducible nitric oxide nitric oxide synthase in a cellular model of arthritis. Luciferase reporter assays confirmed that the miR-181a-5p binding site was in the DDX3X gene 3′-untranslated region (3′-UTR), and DDX3X was negatively regulated by miR-181a-5p. Rescue assays confirmed that miR-181a-5p reduced the expression of DDX3X by targeting the 3′-UTR region of DDX3X, thereby reducing the release of inflammatory factors. Finally, in this paper, western blot was used to detect the mechanism of miR-181a-5p regulating OA. The results showed that interfering with the expression of miR-181a-5p could up-regulate the expression of DDX3X protein, increase the expression of nuclear factor- kappaB (NF-κB) related proteins, and reduce the inflammatory response of OA, thereby increasing the secretion of the matrix proteinases MMP-3 and MMP-13. Taken together, the results of the study suggested that miR-181a-5p may be a promising therapeutic target for the treatment of human OA. [ABSTRACT FROM AUTHOR]

Intervertebral disc degeneration (IVDD) has become a serious public health problem, placing a heavy burden on society and the healthcare system. Its pathogenesis is not completely clear and may be closely related to mechanical damage, inflammatory factors, oxidative stress and death of nucleus pulposus cells (NPCs). The treatment of IVDD mainly includes conservative treatment and surgery. Conservative treatment is based on hormonal and anti-inflammatory drugs and massage techniques, which can relieve the pain symptoms to a certain extent, but cannot solve the problem from the root cause. Surgical treatment is mainly by removing the herniated nucleus pulposus, but it is more traumatic for IVDD patients, expensive and not suitable for all patients. Therefore, it is extremely important to clarify the pathogenesis of IVDD, to find an effective and convenient treatment and to further elaborate its mechanism of action. The effectiveness of traditional Chinese medicine in the treatment of IVDD has been well demonstrated in clinical medical research. We have been working on the Chinese herbal formula Duhuo Jisheng Decoction, which is a common formula for the treatment of degenerative disc disease. Not only does it have significant clinical effects, but it also has few adverse effects. At present, we found that its mechanism of action mainly involves regulation of inflammatory factors, reduction of apoptosis and pyroptosis of NPCs, inhibition of extracellular matrix degradation, improvement of intestinal flora, etc. However, a few relevant articles have yet comprehensively and systematically summarized the mechanisms by which they exert their effect. Therefore, this paper will comprehensively and systematically explain on it. This is of great clinical significance and social value for elucidating the pathogenesis of IVDD and improving the symptoms of patients, and will provide a theoretical basis and scientific basis for the treatment of IVDD with traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Background: There is a characteristic Tibetan folk medicine in China named Corydalis hendersonii Hemsl. (CH) has been used for treatment of cardiovascular related diseases, called "plethora" in Tibetan medicine. Previous studies demonstrated that ethanol extract of CH showed anti-acute myocardial infarction (AMI) effect through inhibiting fibrosis and inflammation. Rich alkaloids fraction (RAF) is isolated from CH, but whether RAF possessing an equivalent effect with the CH ethanol extract and by which mechanism it protects against AMI has not yet reported. The paper aimed to study the potential role of RAF on myocardial injured mice and its underlying mechanism. Materials and methods: Liquid chromatography mass spectrometry-ion trap-time of flight (LCMS-IT-TOF) was used to analyze the chemical profile and isolate pure compounds. The ligation of left anterior descending (LAD) of coronary artery in mice was used to evaluate the in vivo anti-AMI effect, by dividing into eight groups: Sham, Model, Fosinopril (10 mg/kg, i.g.), total extract (TE, 400 mg/kg, i.g.), poor alkaloids fraction (PAF, 300 mg/kg, i.g.), and RAF (25, 50, and 100 mg/kg, respectively, i.g.) groups. Echocardiography was used to evaluate mice heart function through the index of left ventricular end-systolic diameter (LVEDs), left ventricular end-diastolic diameter (LVEDd), fractional shortening (FS) and ejection fraction (EF). We detected the lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the serum and the plasma level of angiotensin II (AngII). The apoptosis of mice myocardial tissue was verified by TUNEL assay. The expression of p38 mitogen-activated protein kinases (p38 MAPK), Bcl-2 and Bcl-2-associated X protein (Bax) were detected through immunofluorescence staining, qRT-PCR and western blot in mice heart tissue and H9c2 cells. Results: Echocardiography data indicated that the values of LVEDd and LVEDs were reduced and the values of FS and EF were improved by TE and RAF significantly. RAF also decreased the levels of LDH, CK-MB and AngII and significantly inhibited inflammatory cells in the marginal zone of myocardial infarction. The TUNEL assay results showed that RAF significantly attenuated cell apoptosis. Immunofluorescence and qRT-PCR assay showed that RAF inhibited p38 MAPK, Bax, and Bcl-2 proteins in mice myocardium. Western blot results validated that the expressions of key proteins were inhibited by RAF. Also, the apoptotic cells and apoptosis-related proteins were dramatically reduced by RAF in vivo and in vitro. Besides, RAF and PAF were analyzed by LCMS-IT-TOF to identify the main compounds and to demonstrate the difference between them. The results showed that a total of 14 alkaloids were identified, which indicated that the isoquinoline alkaloids were the main ingredients in RAF may contributing to the cardioprotective effect in mice. Conclusions: RAF improves cardiac function by inhibiting apoptosis via p38 MAPK signaling pathway, and RAF contributes to the effect against myocardial ischemic injury of TE in mice, which provides a substantial reference for the clinical application against ischemia heart disease and quality control of CH. Highlights: The total extract of Corydalis hendersonii Hemsl. (CH) and the rich alkaloids fraction (RAF) of CH showed significant cardioprotective effect on mice following acute myocardial infarction. RAF improved cardiac function by inhibiting apoptosis via p38 mitogen-activated protein kinases (p38 MAPK) signaling pathway in vitro and in vivo. The results of liquid chromatography mass spectrometry-ion trap-time of flight (LCMS-IT-TOF) showed that the 14 isoquinoline alkaloids in RAF as the main ingredients contribute to the cardioprotective effect. [ABSTRACT FROM AUTHOR]

Background: Pulpal and periodontal healing are two main concerns of delayed replantation of avulsed teeth. The objective of this review was to evaluate the effectiveness of topical and systemic application of tetracyclines on pulpal and periodontal healing after tooth replantation. Methods: A comprehensive electronic search was conducted in six databases. This systematic review was carried out according to Cochrane Handbook and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: After exclusion of 246 irrelevant papers, 14 animal studies and one human study were included in this review. The human study showed that avulsed permanent teeth treated with doxycycline did not show a better clinical outcome for pulp and periodontal healing compared with treatment with normal saline. As for animal studies, significant more pulpal healing was observed in immature teeth treated with topical doxycycline in two researches, while another one study showed that there is no difference between teeth treated with normal saline and teeth treated with doxycycline. Systemic doxycycline exerted no significant effect on pulpal revascularization illustrated by one research. Only one out of four articles illustrated the positive effect of systemic tetracyclines on periodontal healing. One paper reported that intracanal application of demeclocycline promoted favorable periodontal healing. Two articles showed topical doxycycline contributed to favorable periodontal healing, while five studies showed no significant effect of topical tetracyclines on periodontal healing. Conclusions: As a result of data heterogeneity and limitations of the studies, the effect of topical or systemic application of tetracyclines on pulpal and periodontal healing is inconclusive. More studies are required to get more clinically significant conclusions. [ABSTRACT FROM AUTHOR]

Background: We summarize comparative ethnoornithological data for ten Mexican Indigenous communities, an initial step towards a comprehensive archive of the avian diversity conserved within Mexico's Indigenous territories. We do so by counting highlighted species listed for bird conservation status on widely recognized "red lists" and their cultural value to build biocultural policies in Mexico for their conservation. Methods: Indigenous bird names for each study site were determined to allow calculation of the "Scientific Species Recognition Ratio" (SSRR) for high cultural value birds obtained across communities. This demonstrated patterns of cultural prominence. A matrix of 1275 bird versus seven biocultural values was analysed using a correspondence analysis (InfoStat/L-v2020) to illustrate patterns of concordance between bird conservation status and cultural values. Results: This paper contributes to quantitative and qualitative data on the role of ethnoornithology and ethnobiology in biocultural conservation. The areas studied provide refugia for almost 70% of the Mexican avifauna within a fraction of 1% of the national territory, that is 769 bird species recorded for all communities. The global correspondence of regions of biological and linguistic megadiversity is well established, while linguistic diversity is widely accepted as a good proxy for general cultural diversity. Our correspondence analysis explained 81.55% of the variation, indicating a strong relation between cultural importance and bird conservation status. We propose three main categories to establish a bioculturally informed public policy in Mexico for the conservation of what we described as high, medium, and bioculturally prominent bird species all include cultural value in any material or symbolic aspect. High are those species appearing on any threatened list, but also considered in any endemic status, while medium include threatened listed species. The last category included species not necessarily listed on any threat list, but with a wide range of social and cultural uses. We suggest that the concept might be extended to other species of biocultural importance. Conclusions: We argue that bird conservation policies should be biocultural, that is they should recognize birds of cultural value on a par with bird species "of special interest" because they are most critical for biodiversity conservation. The desire of local people to protect their traditional community lands and livelihoods can be an effective biodiversity conservation strategy, which should be recognized in national biocultural policies. [ABSTRACT FROM AUTHOR]

Background: Amyloid β-protein (Aβ) plaque deposition is an important prevention and treatment target for Alzheimer's disease (AD). As a noninvasive, nonradioactive and highly cost-effective clinical imaging method, magnetic resonance imaging (MRI) is the perfect imaging technology for the clinical diagnosis of AD, but it cannot display the plaque deposition directly. This paper resolves this problem based on pixel feature selection algorithms at the image level. Methods and Results: Firstly, the brain region was segmented from mouse model brain MR images. Secondly, the pixels in the segmented brain region were extracted as a feature vector (features). Thirdly, feature selection was conducted on the extracted features, and the optimal feature subset was obtained. Fourthly, the various optimal feature subsets were obtained by repeating the same processing above. Fifthly, based on the optimal feature subsets, the final optimal feature subset was obtained by voting mechanism. Finally, using the final optimal selected features, the corresponding pixels on the MR images could be found and marked to show the information about Aβ plaque deposition. The MR images and brain histological image slices of twenty-two model mice were used in the experiments. Four feature selection algorithms were used on the MR images and six kinds of classification experiments are conducted, thereby choosing a pixel feature selection algorithm for further study. The experimental results showed that by using the pixel features selected by the algorithms in this paper, the best classification accuracy between early AD and control slides could be as high as 80 %. The selected and marked MR pixels could show information of Aβ plaque deposition without missing most of the Aβ plaque deposition compared with brain histological slice images. The hit rate is over than 90 %. Conclusions: According to the experimental results, the proposed detection algorithm of the Aβ plaque deposition based on MR pixel feature selection algorithm is effective. The proposed algorithm can detect the information of the Aβ plaque deposition on MR images and the information can be useful for improving the classification accuracy as assistant MR biomarker. Besides, these findings firstly show the feasibility of detection of the Aβ plaque deposition on MR images and provide reference method for interested relevant researchers in public. [ABSTRACT FROM AUTHOR]

Background: Morinda citrifolia (Noni) is a plant that has long been used in various products such as foods and cosmetics. Although noni has been known to have immunostimulatory activity, detailed mechanism at the cellular level has not been fully elucidated yet. In this study, we focused on understanding as to how noni fruit can positively stimulate body's immune responses. Methods: To do this, an ethanol extract of noni fruit (Mc-fEE) was prepared and administered for 30 days to male C57BL/6 mice for in vivo experiment. NK cell activity and cytokine production level from Mc-fEE-treated mice were analyzed by flowcytometry, real-time PCR, and ELISA. Mc-fEE-triggered molecular events were detected from RAW264.7 cells and splenocytes using Western blotting and real-time PCR analyses. Results: The mRNA expression levels of cytokines such as interleukin families, interferon (IFN)-β, and tumor necrosis factor (TNF)-α were increased by Mc-fEE treatment in vitro and in vivo. Western blotting analysis showed that the phosphorylation levels of nuclear factor (NF)-κB and activator protein (AP)-1 subunits these were enhanced in Mc-fEE-treated RAW264.7 cells. In addition, according to in vivo experiments, it was considered that Mc-fEE can increase the population of splenic NK cells and subsequent upregulation of their cytotoxic activity against YAC-1 cells, a T- cell lymphoma. Conclusion: In this paper, we could confirm that Mc-fEE has remarkable immunostimulatory effects by activation and increase of the NK cell population. [ABSTRACT FROM AUTHOR]

Distraction osteogenesis (DO) is an emerging method for bone tissue reconstruction. In oral and maxillofacial reconstruction applications, DO is playing an important role as a technique without the need of bone graft. In addition, in a DO treatment procedure, a superior outcome could be achieved compared to conventional reconstruction techniques. Recently, a few automatic continuous distraction osteogenesis (ACDO) devices have been designed and developed to be used in human reconstruction applications. Experiments and animal studies have validated the functionality of the developed ACDO devices. It has shown that by using such ACDO devices in a DO procedure, compared to conventional manual DO methods, superior outcomes could be obtained. However, the application of such ACDO devices is still limited. More research and investigation need to be undertaken to study all requirements of ACDO devices to be used in successful human mandibular DO treatment. It is important to determine all requirements and standards that need to be considered and applied in the design and development of ACDO devices. The purpose of this review paper is to highlight the designed and developed ACDO procedures thus far in terms of their working principles, working parameters, and technical aspects for providing a better perspective of the development progress of ACDO devices for oral and maxillofacial reconstruction applications. In this paper, design principles, device specifications, and working parameters of ACDO devices are compared and discussed. Subsequently, current limitations and gaps have been addressed, and future works for enabling an ultimate automatic DO procedure have been suggested. [ABSTRACT FROM AUTHOR]

In this paper, the in-vivo healing of critical-sized bony defects by cell-free and stem cell-seeded 3D-printed PLA scaffolds was studied in rat calvaria bone. The scaffolds were implanted in the provided defect sites and histological analysis was conducted after 8 and 12 weeks. The results showed that both cell-free and stem cell-seeded scaffolds exhibited superb healing compared with the empty defect controls, and new bone and connective tissues were formed in the healing site after 8 and 12 weeks, postoperatively. The higher filled area, bone formation and bone maturation were observed after 12 weeks, particularly for PLA + Cell scaffolds. [ABSTRACT FROM AUTHOR]

Introduction: Randomized and nonrandomized clinical trials have tried to assess whether or not TMR patients experience an increase in myocardial perfusion. However there have been inconsistencies reported in the literature due to the use of different nuclear imaging modalities to test this metric. The primary purpose of this meta-analysis was to determine whether SPECT, MUGA and PET scans demonstrate changes in myocardial perfusion between lased and non-lased subjects and whether laser type affects myocardial perfusion. The secondary purpose was to examine the overall effect of laser therapy on clinical outcomes including survival, hospital re-admission and angina reduction.Methods: Sixteen studies were included in the primary endpoint analysis after excluding all other non-imaging TMR papers. Standardized mean difference was used as the effect size for all quantitative outcomes and log odds ratio was used as the effect size for all binary outcomes.Results: Statistically significant improvements in myocardial perfusion were observed between control and treatment groups in myocardial perfusion at 6-month follow up using PET imaging with a porcine model. However non-significant differences were observed in patients at 3 and 12 months using SPECT, PET or MUGA scans. Both CO2 and Ho:YAG laser systems demonstrated an increase in myocardial perfusion however this effect was not statistically significant. In addition both laser types displayed statistically significant decreases in patient angina at 3, 6 and 12 months but non-significant increases in survival rates and decreases in hospital re-admissions.Conclusion: In order to properly assess myocardial perfusion in TMR subjects, subendocardial perfusion needs to be analyzed via nuclear imaging. PET scans can provide this level of sensitivity and should be utilized in future studies to monitor and detect perfusion changes in lased and non-lased subjects. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. Objective: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. Methods: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1β concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. Results: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). Conclusions: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA. [ABSTRACT FROM AUTHOR]

Background: Several local communities in Central, Western, Eastern, and Northern regions of Uganda have been using the whole leaf extracts of Aloe vera (L.) Burm. f. (Asphodelaceae) in the treatment of various ailments. Also, several commercial companies sell A. vera as soft drinks in Uganda. However, there are inadequate reports on the toxicities of such preparations. This paper reports the acute and sub-acute oral toxicity of aqueous extracts of whole leaf and green rind of A. vera in Wistar rats. Methods: Acute oral toxicity test was carried out in female Wistar rats at doses of 175, 550, 1750, and 5000 mg/kg, p.o. The animals were observed for signs of toxicity for 14 days. Similarly, a sub-acute oral toxicity test was performed in both sexes of rats at doses of 200, 400, and 800 mg/kg, p.o. daily for 28 days. All the groups of animals were monitored for behavioral, morphological, biochemical, and physiological changes, including mortality and compared with respective controls. Body weights were measured weekly while the animals' relative organ weights, hematological, biochemical, gross, and microscopic pathology were examined on day 29. Results: There was no mortality or apparent behavioral changes at the doses tested in acute and sub-acute oral toxicity tests. Thus, the Median Lethal Dose (LD50) of green rind and whole leaf aqueous extracts was above 5000 mg/kg. Gross anatomy revealed that the rats' relative spleen weight in green rind extract at 200 mg/kg significantly decreased compared to the control group. The creatinine levels in female rats that received green rind extract and the chloride ion levels in male rats administered whole leaf extract were significantly elevated. Conversely, Mean Corpuscular Hemoglobin Concentration (MCHC) levels significantly decreased at lower doses of the green rind extract compared to the control. Histopathology of the kidney revealed the renal interstitium's inflammation at doses of 200 and 800 mg/kg of the whole leaf extract. Conclusion: The findings demonstrated that A. vera green rind and whole leaf extracts are non-toxic at relatively high doses when used for a short duration. Prolonged use of the aqueous whole leaf extract might be associated with kidney toxicity. [ABSTRACT FROM AUTHOR]

Background: As a prevalent type of cryptogenic fibrotic disease with high mortality, idiopathic pulmonary fibrosis (IPF) still lacks effective therapeutic drugs. The compounds extracted from buds and flowers of Chrysanthemum indicum Linné with supercritical-carbon dioxide fluid (CISCFE) has been confirmed to have antioxidant, anti-inflammatory, and lung-protective effects. This paper aimed to clarify whether CISCFE could treat IPF induced by bleomycin (BLM) and elucidate the related mechanisms. Methods: Rats (Sprague-Dawley, male) were separated into the following groups: normal, model, pirfenidone (50 mg/kg), CISCFE-L, −M, and -H (240, 360, and 480 mg/kg/d, i.g., respectively, for 4 weeks). Rats were given BLM (5 mg/kg) via intratracheal installation to establish the IPF model. A549 and MRC-5 cells were stimulated by Wnt-1 to establish a cell model and then treated with CISCFE. Haematoxylin-eosin (H&E) and Masson staining were employed to observe lesions in the lung tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) were performed to observe changes in genes and proteins connected with the Wnt/β-catenin pathway. Results: CISCFE inhibited the proliferation of MRC-5 cells (IC50: 2.723 ± 0.488 μg/mL) and A549 cells (IC50: 2.235 ± 0.229 μg/mL). In rats, A549 cells, and MRC-5 cells, BLM and Wnt-1 obviously induced the protein expression of α-smooth muscle actin (α-SMA), vimentin, type I collagen (collagen-I), and Nu-β-catenin. The mRNA levels of matrix metalloproteinase-3 (MMP-3) and − 9 (MMP-9), two enzymes that degrade and reshape the extracellular matrix (ECM) were also increased while those of tissue inhibitor of metalloproteinase 1 (TIMP-1) were decreased. However, CISCFE reversed the effects of BLM and Wnt-1 on the expression pattern of these proteins and genes. Conclusion: These findings showed that CISCFE could inhibit IPF development by activating the Wnt/β-catenin pathway and may serve as a treatment for IPF after further investigation. [ABSTRACT FROM AUTHOR]

Background: The burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research., Methods: We conducted a systematic review of the ethical literature concerning human-animal chimeras based on the research question: "What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?" Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected., Results: Four hundred thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types. 15% of the retrieved passages contained reasons in favor of conducting chimera research (Category P), while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera (Category A), its treatment (Category B), reasons referring to metaphysical or social issues resulting from its existence (Category C) and to potential downstream effects of chimera research (Category D). A significant proportion of identified passages (46%) fell under Category C., Conclusions: We hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation.

Background: Non-small-cell lung cancer (NSCLC) accounts more than 80% of the lung cancer cases. Polysaccharides in rice bran and its fermentation products have been proven to suppress many cancers. However, the report on inhibiting NSCLC is few. In this paper, the polysaccharides with suppression activity to H1299 NSCLC in the fermentation products of full-fat rice bran and defatted rice bran were studied in vitro and in vivo. Method: Polysaccharides (GSRBPs) were extracted from Ganoderma sinense – full-fat rice bran (GS-FRB) and Ganoderma sinense – defatted rice bran (GS-DRB) fermentation products. The structure information of the GSRBPs was studied using HPLC analysis. The anti-tumor activities on H1299 NSCLC of GSRBPs in vitro study was performed using MTT method. The in vivo studies use BALB/c-nu nude mice as H1299 NSCLC bearing mice. Result: All the polysaccharides contained two fractions, GSFPS-1 and GSFPS-2. The molecular weight and the ratio of GSFPS-1 and GSFPS-2 were different in GS-FRB and GS-DRB. At the earlier state of fermentation, all polysaccharides were composed of D-glu, D-man, D-xyl and L-ara with certain molar ratios. But at the latter stage, polysaccharides in GS-FRB were composed of D-glu, D-man, D-xyl, L-ara and D-fru, while these in GS-DRB only composed of D-glu and D-man. In the in vitro study, the IC50 of RBS and GSRBPs was as GS-DRB-11 (40.62 μg/mL), GS-FRB-9 (43.82 μg/mL), GS-DRB-7 (48.08 μg/mL), RBS (49.56 μg/mL), GS-DRB-9 (49.91 μg/mL), GS-DRB-13 (51.89 μg/mL), GS-FRB-11 (53.75 μg/mL), GS-FRB-7 (56.84 μg/mL), GS-DRB-13 (60.63 μg/mL) from small to large. In the in vivo study, the H1299 NSCLC inhibition rate (InRa) of RBS and GSRBPs were GS-DRB-11 (86.81%) > GS-DRB-9 (86.01%) > GS-FRB-9 (84.88%) > GS-DRB-7 (82.21%) > GS-DRB-13 (78.04%) > RBS (76.06%) > GS-FRB-13 (65.44%) > GS-FRB-11 (64.70%) > GS-FRB-7 (27.87%). The GSFPS-2 area percent was negatively correlated to the IC50 and was positively correlated to the InRa. This means the GSFPS-2 had much higher anti-tumor activity than GSFPS-1. Conclusion: GSFPS-2 had higher anti-tumor activities, and the lipid in the rice bran has a decisive effect on the structures of polysaccharides produced by fermentation. Therefore, GSRBPs could be considered as potential novel agents to suppress H1299 non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Background: Participation in on-the-land programs that encourage traditional cultural activities may improve health and well-being. The Income Security Program (ISP) - a financial incentive-based on-the-land program - for Eeyouch (Cree) hunters and trappers in Eeyou Istchee was created as a result of the 1975 James Bay and Northern Quebec Agreement to help mitigate the effects of hydroelectric development on the Cree people of northern Quebec, Canada. Beyond the ISP's financial incentives, little is known about the health measures of those who are eligible to participate in the ISP (i.e. spent ≥120 days on-the-land during the previous year). Therefore, this paper's objective was to assess the health measures of northern Quebec Cree, who were eligible for participation in the ISP.Methods: Using participant data (n = 545) compiled from the Nituuchischaayihtitaau Aschii Multi-Community Environment-and-Health Study, we assessed 13 different health measures in generalized linear models with the independent variable being the eligibility to participate in the ISP.Results: Participants in the present study who were eligible for the ISP had significantly higher levels of vigorous and moderate activity per week, and higher concentrations of omega-3 polyunsaturated fatty acids in the blood compared to those ineligible for the ISP (i.e. spent ≤119 days on-the-land during the previous year). Encouragingly, following model adjustment for age and sex, participants eligible for the ISP did not have higher blood concentrations of mercury than those who were not eligible for the ISP.Conclusions: Our results suggest that the participants eligible for participation in the ISP are likely to be healthier than those who are ineligible to participate - and are promising for on-the-land programs for Indigenous peoples beyond a financial incentive - with no apparent higher risk of increasing contaminant body burden through traditional on-the-land-activities (e.g. fish consumption). [ABSTRACT FROM AUTHOR]

Background: Rodent models of liver resection have been used to investigate and evaluate the liver's complex physiology and pathology since 1931. First documented by Higgins and Anderson, such models were created to understand liver regeneration mechanisms to improve outcomes in patients undergoing extensive liver resection for liver cancer or other underlying liver diseases. Methods: A systematic search was conducted using Pubmed, gathering publications up to January 2019, which engaged with the mouse model of extended liver resection as a method itself. The results of this search were filtered according to their language, novelty, and relevancy. Results: The Boolean search found 3741 articles on Pubmed, with 3130 publications remaining when filtered by language and the presence of a full text. In total, 21 of these publications examined the key themes of the animal model described. The mortality varied from 0 to 50% depending on the surgeon's experience and the resection method. The liver resection was mainly performed with classic sutures (14 out of 21 publications) and isoflurane was used for anaesthesia (10 out of 21 publications) in combination with analgesics (buprenorphine or ketamine/xylazine). The most used mouse strain was C57BL/6 (7 of 21 publications) which was on average 11 weeks old with a weight of 23 g. Conclusion: Through the overview, laid out in the selected publications, this paper reviews the shift of the extended liver resection model from rat to the mouse, describes the state of the art in the experimental setting, and discusses the possible limitations and pitfalls. Clearly, the extended liver resection in mice is a reproducible, practical and easy to learn method. [ABSTRACT FROM AUTHOR]

Background: Ulcerative colitis (UC) is an intestinal disease which was characterized by intestinal inflammation, mucosal injury and fibrosis. In this paper, the effect of Huanglian Jiedu Decoction (HJD), a well-known traditional Chinese medicine with significant anti-inflammatory effect, on dextran sulphate sodium (DSS)-induced UC in mice and inhibition of JAK2/STAT3 pathway were investigated. Methods: BALB/c mice were randomly divided into 6 groups: HJD group (high, medium and low dose), USAN group, UC group, and control group. UC in mice were induced through free access to 3% DSS solution. After being treated with HJD for 8 days, all animals were sacrifice. Pathological examination of colonic specimen was performed by H&E staining. Cytokines (TNF-α, IL-6, and IL-1β) in colon were assayed by ELISA and immunofluorescence, MPO in colon and ATT in serum were detected by ELISA. Moreover, mice in HJD group and UC group were treated with AG490 to inhibit the expression of JAK2 protein, then the expression of JAK2 and STAT3 protein in colon was determined by western blotting and immunofluorescence staining. Furthermore, KI67 in colon was examined by immunohistochemistry, and apoptosis was detected by TUNEL staining, and collagen deposition was assayed by Masson staining after JAK2/STAT3 pathway in UC mice was inhibited by HJD. Results: After mice being treated with HJD, the symptoms (weight loss and haematochezia) of UC were alleviated, and the contents of inflammatory cytokines (TNF-α, IL-6 and IL-1β) and MPO in colon were significantly decreased. The expression of JAK2 and STAT3 protein was reduced after administration with HJD. After JAK2/STAT3 pathway being inhibited with HJD, the cell apoptosis, collagen deposition and immunoreactivity of macrophage in colon were significantly reduced, but the expression of Ki67 was markedly enhanced in both UC group and HJD group compare with control group. Conclusions: HJD treatment can alleviate intestinal mucosal damage and has the protective effect on UC by downregulating JAK2 and STAT3 expression to reduce inflammation via JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: Local people's interaction with bats render them vulnerable to Ebola Virus Disease (EVD). This paper examines perceptions of risk involved in the hunting, handling, processing and consumption of bat meat in the Mount Cameroon region of Southwest Cameroon. It focuses on the myriad cultural beliefs, gendered patterns of activity and institutional arrangements in which the bat meat production chain is embedded.Methods: We conducted 30 ethnographic interviews with a sample of purposively selected men and women involved in the bat meat trade. The interviews were tape recorded, transcribed verbatim and inductive analysis was performed on the data.Findings: The findings suggests that more urban men than villagers and hunters consume bat meat. Different practices and behaviours expose the mostly uneducated, young, single men and women to the risk of Ebola infection depending on their differential level of intervention in the human-bat interaction and value chain linking hunters, sellers and customers. The killing of bats with the mouth during hunting expose hunters (young men) while the preparation of bat carcasses for consumption also put women, (mostly young and unmarried) at risk.Conclusions: This study demonstrates that the complexity and nuances of gender, poverty and Ebola outcomes predispose some marginal groups to the risk of infection with zoonotic diseases. There is the need to improve public health intervention and health education among the rural masses in the Mount Cameroon region. [ABSTRACT FROM AUTHOR]

Background: Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism. Methods: The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment I / R group (12.5, 25, 50 mg / kg). After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins. Results: Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression. Conclusion: The antioxidant properties of astragalin may play an important role in improving cerebral ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: Paracoccidioidomycosis, a chronic granulomatous fungal disease caused by Paracoccidioides brasiliensis yeast cells affects mainly rural workers, albeit recently cases in immunosuppressed individuals has been reported. Protective immune response against P. brasiliensis is dependent on the activity of helper T cells especially IFN-γ-producing Th1 cells. It has been proposed that Paracoccidioides brasiliensis is able to modulate the immune response towards a permissive state and that the thymus plays a major role in it.Methods: In this paper, we show that acute infection of BALB/c mice with P. brasiliensis virulent isolate (Pb18) might cause alterations in the thymic environment as well as the prohibitive TCR-expressing T cells in the spleens.Results: After seven days of infection, we found yeast cells on the thymic stroma, the thymic epithelial cells (TEC) were altered regarding their spatial-orientation and inflammatory mediators gene expression was increased. Likewise, thymocytes (differentiating T cells) presented higher migratory ability in ex vivo experiments. Notwithstanding, P. brasiliensis-infected mice showed an increased frequency of prohibitive TCR-expressing T cells in the spleens, suggesting that the selection processes that occur in the thymus may be compromised during the acute infection.Conclusion: In this paper, for the first time, we show that acute infection with Paracoccidioides brasiliensis yeast cells promotes thymic alterations leading to a defective repertoire of peripheral T cells. The data presented here may represent new mechanisms by which P. brasiliensis subverts the immune response towards the chronic infection observed in humans. [ABSTRACT FROM AUTHOR]

Background: Nanostructured materials used have unique properties and many uses in nanotechnology. The most striking of these is using herbal compounds for the green synthesis of nanoparticles. Among the nanoparticle types used for green synthesis, gold nanoparticles (AuNPs) are used for cancer therapy due to their stable structure and non-cytotoxic. Lung cancer is the most common and most dangerous cancer worldwide in terms of survival and prognosis. In this study, Nasturtium officinale (L.) extract (NO), which contains biomolecules with antioxidant and anticancer effects, was used to biosynthesize AuNPs, and after their characterization, the effect of the green-synthesized AuNPs against lung cancer was evaluated in vitro. Methods: Ultraviolet‒visible (UV‒Vis) spectrophotometry, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy (EDS), multiple analysis platform (MAP), and Fourier transform infrared (FT-IR) spectroscopy analyses were performed to characterize the AuNPs prepared from the N. officinale plant extract. Moreover, the antioxidant activity, total phenolic and flavonoid contents and DNA interactions were examined. Additionally, A549 lung cancer cells were treated with 2–48 µg/mL Nasturtium officinale gold nanoparticles (NOAuNPs) for 24 and 48 h to determine the effects on cell viability. The toxicity of the synthesized NOAuNPs to lung cancer cells was determined by the 3-(4,5-dimethylthiazol-2-il)-2,5-diphenyltetrazolium bromide (MTT) assay, and the anticancer effect of the NOAuNPs was evaluated by apoptosis and cell cycle analyses using flow cytometry. Results: The average size of the NPs was 56.4 nm. The intensities of the Au peaks from EDS analysis indicated that the AuNPs were synthesized successfully. Moreover, the in vitro antioxidant activities of the NO and NOAuNPs were evaluated; these materials gave values of 31.78 ± 1.71% and 31.62 ± 0.46%, respectively, in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay at 200 g/mL and values of 25.89 ± 1.90% and 33.81 ± 0.62%, respectively, in the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay. The NO and NOAuNPs gave values of 0.389 ± 0.027 and 0.308 ± 0.005, respectively, in the ferrous ion reducing antioxidant capacity (FRAP) assay and values of 0.078 ± 0.009 and 0.172 ± 0.027, respectively, in the copper ion reducing antioxidant capacity (CUPRAC) assay. When the DNA cleavage activities of NO and the NOAuNPs were evaluated via hydrolysis, both samples cleaved DNA starting at a concentration of 25 g/mL in the cell culture analysis, while the nanoformulation of the NO components gave greater therapeutic and anticancer effects. We determined that the Au nanoparticles were not toxic to A549 cells. Moreover, after treatment with the half-maximal inhibitory concentration (IC50), determined by the MTT assay with A549 cells, we found that at 24 and 48 h, while the necrosis rates were high in cells treated with NO, the rates of apoptosis were greater in cells treated with NOAuNPs. Notably, for anticancer treatment, activating apoptotic pathways that do not cause inflammation is preferred. We believe that these results will pave the way for the use of NOAuNPs in in vitro studies of other types of cancer. Conclusion: In this study, AuNPs were successfully synthesized from N. officinale extract. The biosynthesized AuNPs exhibited toxicity to and apoptotic effects on A549 lung cancer cells. Based on these findings, we suggest that green-synthesized AuNPs are promising new therapeutic agents for lung cancer treatment. However, since this was an in vitro study, further research should be performed in in vivo lung cancer models to support our findings and to explain the mechanism of action at the molecular level. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway. [ABSTRACT FROM AUTHOR]

Background: Xuefu Zhuyu decoction (XFZYD) has been extensively utilized to treat traumatic brain injury (TBI). However, the bioactive compounds and the underlying mechanisms have not yet been elucidated. Objectives: This study aimed to investigate the bioactive constituents of XFYZD that are absorbed in the blood and the mechanisms in treating TBI. Methods: The study presents an integrated strategy in three steps to investigate the material basis and pharmacological mechanisms of XFZYD. The first step involves: (1) performing metabolomics analysis of XFZYD to obtain the main functions and targets; (2) screening the blood-entry ingredients and targets of XFZYD from databases; (3) obtaining the potential components targeting the key functions by integrated analysis of metabolomics and network pharmacology. The second step involves screening pharmacological effects with active ingredients in vitro. In the third step, the effects of the top active compound were validated in vivo, and the mechanisms were explored by protein antagonist experiments. Results: Metabolomics analysis revealed that XFZYD treated TBI mice mainly through affecting the functions of blood vessels. We screened 62 blood-entry ingredients of XFZYD by network pharmacology. Then, we focused on 39 blood-entry ingredients related to vascular genes enriched by XFZYD-responsive metabolites. Performing the natural products library, we verified that hydroxysafflor yellow A (HSYA), vanillin, ligustilide, paeoniflorin, and other substances promoted endothelial cell proliferation significantly compared to the control group. Among them, the efficacy of HSYA was superior. Further animal studies demonstrated that HSYA treatment alleviated neurological dysfunction in TBI mice by mNSS and foot fault test, and decreased neuronal damage by HE, nissl, and TUNEL staining. HSYA increased the density of cerebral microvessels, raised the expression of angiogenesis marker proteins VEGFA and CD34, and activated the PI3K/Akt/mTOR signaling pathway significantly. The angiogenic effects disappeared after the intervention of PI3K antagonist LY294002. Conclusion: By applying a novel strategy of integrating network pharmacology of constituents absorbed in blood with metabolomics, the research screened HSYA as one of the top bioactive constituents of XFZYD, which stimulates angiogenesis by activating the PI3K/Akt/mTOR signaling pathway after TBI. [ABSTRACT FROM AUTHOR]

Pancreatic cancer is a devastating malignancy with a high mortality rate, poor prognosis, and limited treatment options. The tumor microenvironment (TME) plays a crucial role in tumor progression and therapy resistance. Multiple subpopulations of cancer-associated fibroblasts (CAFs) within the TME can switch between different states, exhibiting both antitumorigenic and protumorigenic functions in pancreatic cancer. It seems that targeting fibroblast-related proteins and other stromal components is an appealing approach to combat pancreatic cancer. This study employed single-cell transcriptome sequencing to identify MME (Membrane Metalloendopeptidase)-expressing CAFs in pancreatic cancer. Systematic screening was conducted based on tumor differentiation, lymph node metastasis, and T-stage parameters to identify and confirm the existence of a subpopulation of fibroblasts termed MME+CAFs. Subsequent analyses included temporal studies, exploration of intercellular communication patterns focusing on the hypoxia signaling pathway, and investigation of MME+CAF functions in the pancreatic cancer microenvironment. The pathway enrichment analysis and clinical relevance revealed a strong association between high MME expression and glycolysis, hypoxia markers, and pro-cancer inflammatory pathways. The role of MME+CAFs was validated through in vivo and in vitro experiments, including high-throughput drug screening to evaluate potential targeted therapeutic strategies. Single-cell transcriptome sequencing revealed tumor-associated fibroblasts with high MME expression, termed MME+CAF, exhibiting a unique end-stage differentiation function in the TME. MME+CAF involvement in the hypoxia signaling pathway suggested the potential effects on pancreatic cancer progression through intercellular communication. High MME expression was associated with increased glycolysis, hypoxia markers (VEGF), and pro-cancer inflammatory pathways in pancreatic cancer patients, correlating with lower survival rates, advanced disease stage, and higher oncogene mutation rates. Animal experiments confirmed that elevated MME expression in CAFs increases tumor burden, promotes an immunosuppressive microenvironment, and enhances resistance to chemotherapy and immunotherapy. The developed MME+CAF inhibitor IOX2 (a specific prolyl hydroxylase-2 (PHD2) inhibitor), combined with AG (Paclitaxel + Gemcitabine) and anti-PD1 therapy, demonstrated promising antitumor effects, offering a translational strategy for targeting MME in CAFs of pancreatic cancer. The study findings highlighted the significant role of MME+CAF in pancreatic cancer progression by shaping the TME and influencing key pathways. Targeting MME presented a promising strategy to combat the disease, with potential implications for therapeutic interventions aimed at disrupting MME+CAF functions and enhancing the efficacy of pancreatic cancer treatments. [ABSTRACT FROM AUTHOR]

Background: Bisphosphonates (BPs) are widely used to inhibit excessive osteoclast activity. However, the potential to compromise bone defect healing has limited their broader application. To better understand the influence of BPs on bone regeneration, we established a bone grafting model with Zoledronate administration, aiming to deepen the understanding of bone remodeling and mineralization processes. Methods: A bone grafting model was established in the distal femurs of male Sprague–Dawley rats. The experimental group received systemic administration of Zoledronate (ZOL, 0.2 mg/kg, administered twice). Histological analysis and immunohistochemistry (IHC) were employed to assess osteoblastic and macrophage activity, tartrate-resistant acid phosphatase (TRAP) staining was used to evaluate osteoclastogenesis. Mineralization was assessed through Micro-CT analysis, Raman spectroscopy, and back-scatter scanning electron microscopy (BSE-SEM). Additionally, the in vitro effects of ZOL on osteoblast and osteoclast activity were investigated to further elucidate its impact on bone regeneration. Results: In vivo, the ZOL group showed increased bone mass, as observed in histological and radiological assessments. However, Micro-CT, Raman spectroscopy, and BSE-SEM detection revealed lower mineralization levels in ZOL group's regenerated bone. Acid-etched SEM analysis showed abnormal osteocyte characteristics in ZOL-group's regenerated bone. Simultaneously, elevated osteopontin (OPN), F4/80 expression along with reduced TRAP expressing was found in the grafting region of ZOL group. In vitro, ZOL did not negatively impact osteogenetic activity (ALP, BMP4, OCN expression) at the tested concentrations (0.02–0.5 g/ml) but significantly impaired mineralization and inhibited osteoclast formation, even at the lowest concentration. Conclusions: This study highlights a less recognized negative effect of ZOL on bone mineralization during bone regeneration. More research is needed to elucidate the underlying mechanism. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the impact of virtual simulation experiment teaching model and Massive Open Online Course (MOOC) teaching model on the teaching effect in debridement teaching. Methods: The study adopted a quasi-experimental design and used virtual simulation technology to construct a virtual simulation experimental teaching platform for debridement. This study was conducted at the Second Clinical College of Wuhan University. The experimental group was composed of 135 third-year clinical medicine students in the 2020 grade, who received the virtual simulation experimental teaching model; the control group was 122 third-year students in the same major in the 2019 grade, who used the MOOC teaching model. The performance of the two groups of students was evaluated through theoretical tests and animal experiment operation. In addition, the effectiveness of the experimental teaching model and student satisfaction were evaluated through questionnaire surveys. Results: The theoretical test scores and animal experiment report scores of the experimental group were significantly higher than those of the control group, and the debridement animal experiment operation time of the experimental group was shorter than that of the control group, and the difference was statistically significant (P < 0.05). The post-class questionnaire survey of the experimental group showed that most students were satisfied with the virtual simulation experimental teaching model and believed that it represented the future teaching trend. Conclusions: In the teaching of debridement, virtual simulation experiment is an effective t teaching model, which not only helps to improve student performance, but also significantly reduces skill operation time and is recognized by students. [ABSTRACT FROM AUTHOR]

Introduction: Acute lung injury (ALI) as one kind of acute pulmonary inflammatory disorder, manifests primarily as damage to alveolar epithelial cells and microvascular endothelial cells. Activation of the complement system is a common pathological mechanism in ALI induced by diverse factors, with the complement alternative pathway assuming a pivotal role. Baicalin, a flavonoid derived from the root of Scutellaria baicalensis Georgi, exhibits noteworthy biological activities. The present study attempted the interventional effects and underlying mechanisms of baicalin in microangiopathy in ALI induced by complement alternative pathway activation. Methods: Activation of the complement alternative pathway by cobra venom factor (CVF). HMEC cells were pretreated with baicalin and then exposed to complement activation products. The expression of inflammatory mediators was detected by ELISA, and the intranuclear transcriptional activity of NF-κB was assessed by a dual fluorescent kinase reporter gene assay kit. Before establishing the ALI mouse model, baicalin or PDTC was gavaged for 7 d. CVF was injected into the tail vein to establish the ALI model. The levels of inflammatory mediators in BALF and serum were determined by ELISA. HE staining and immunohistochemistry evaluated pathological changes, complement activation product deposition, and NF-κB p65 phosphorylation in lung tissue. Results: Baicalin reduced complement alternative activation product-induced expression of HMEC cells adhesion molecules (ICAM-1, VCAM-1, E-selectin) and cytokines (IL-6, TNF-α) as well as upregulation of NF-κB intranuclear transcriptional activity. Baicalin intervention reduced the number of inflammatory cells and protein content in the BALF and decreased the levels of IL-6, TNF-α, and ICAM-1 in serum and IL-6, TNF-α, ICAM-1, and P-selectin in BLAF. In addition, baicalin attenuated inflammatory cell infiltration in the lung of ALI mice and reduced the deposition of complement activation products (C5a, C5b-9) and phosphorylation of NF-κB p65 in lung tissue. Conclusion: Baicalin relieves complement alternative pathway activation-induced lung inflammation by inhibition of NF-κB pathway, delaying the progression of ALI. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most diagnosed cancer in women. Its pathogenesis includes several pathways in cancer proliferation, apoptosis, and metastasis. Some clinical data have indicated the association between coffee consumption and decreased cancer risk. However, little data is available on the effect of coffee on breast cancer cells in vitro and in vivo. Methods: In our study, we assessed the effect of Turkish coffee and Fridamycin-H on different pathways in breast cancer, including apoptosis, proliferation, and oxidative stress. A human breast cancer cell line (MCF-7) was treated for 48 h with either coffee extract (5% or 10 v/v) or Fridamycin-H (10 ng/ml). Ehrlich solid tumors were induced in mice for in vivo modeling of breast cancer. Mice with Ehrlich solid tumors were treated orally with coffee extract in drinking water at a final concentration (v/v) of either 3%, 5%, or 10% daily for 21 days. Protein expression levels of Caspase-8 were determined in both in vitro and in vivo models using ELISA assay. Moreover, P-glycoprotein and peroxisome proliferator-activated receptor gamma (PPAR-γ) protein expression levels were analyzed in the in vitro model. β-catenin protein expression was analyzed in tumor sections using immunohistochemical analysis. In addition, malondialdehyde (MDA) serum levels were analyzed using colorimetry. Results: Both coffee extract and Fridamycin-H significantly increased Caspase-8, P-glycoprotein, and PPAR-γ protein levels in MCF-7 cells. Consistently, all doses of in vivo coffee treatment induced a significant increase in Caspase-8 and necrotic zones and a significant decrease in β- catenin, MDA, tumor volume, tumor weight, and viable tumor cell density. Conclusion: These findings suggest that coffee extract and Fridamycin-H warrant further exploration as potential therapies for breast cancer. [ABSTRACT FROM AUTHOR]

Background: Natural products have a long history in drug discovery. Lycorine is an alkaloid derived from Amaryllidaceae plants, demonstrating significant pharmacological potential. Lycorine and its hydrochloride salt, lycorine hydrochloride, have shown outstanding anticancer effects both in vitro and in vivo. Purpose: This review aims to comprehensively summarize recent research advancements regarding the anticancer potential of lycorine and lycorine hydrochloride. It intends to elucidate current research limitations, optimization strategies, and future research directions to guide clinical translation. Methods: Various databases, e.g., Web of Science, PubMed, and Chinese National Knowledge Infrastructure, are systematically searched for relevant articles using keywords such as lycorine, cancer, pharmacokinetics, and toxicity. The retrieved literature is then categorized and summarized to provide an overview of the research advancements in the anticancer potential of lycorine and lycorine hydrochloride. Results: Lycorine and lycorine hydrochloride demonstrate significant anticancer activities against various types of cancer both in vitro and in vivo, employing diverse mechanisms such as inducing cell cycle arrest, triggering cellular senescence, regulating programmed cell death, inhibiting angiogenesis, suppressing metastasis, and modulating immune system. Furthermore, pharmacokinetic profiles and toxicity data are summarized. Additionally, this review discusses the druggability, limitations, optimization strategies, and target identification of lycorine, offering insights for future preclinical studies. Conclusion: The anticancer effects and safety profile of lycorine and lycorine hydrochloride suggest promising potential for clinical applications. Further research on their in-depth mechanisms and optimization strategies targeting their limitations will enhance the understanding and druggability of lycorine and lycorine hydrochloride. [ABSTRACT FROM AUTHOR]

Background: Facilitating the healing process of injured anterior cruciate ligament (ACL) tissue is crucial for patients to safely return to sports. Stem cell derived exosomes have shown positive effects on enhancing the regeneration of injured tendons/ligaments. However, clinical application of exosomes in terms of storage and pre-assembly is challenging. We hypothesized that lyophilized exosomes derived from human umbilical cord stem cells (hUSC-EX) could enhance the cell activity of chronically injured ACL cells. Materials and methods: We harvested the 8 weeks injured ACL cells from rabbit under IACUC (No. 110232) approval. The studied exosomes were purified from the culture medium of human umbilical cord stem cells (IRB approval No. A202205014), lyophilized to store, and hydrated for use. We compared exosome treated cells with non-exosome treated cells (control group) from the same rabbits. We examined the cell viability, proliferation, migration capability and gene expression of type I and III collagen, TGFβ, VEGF, and tenogenesis in the 8 weeks injured ACL cells after hUSC-EX treatment. Results: After hydration, the average size of hUSC-EX was 84.5 ± 70.6 nm, and the cells tested positive for the Alix, TSG101, CD9, CD63, and CD81 proteins but negative for the α-Tubulin protein. After 24 h of treatment, hUSC-EX significantly improved the cell viability, proliferation and migration capability of 8 weeks injured ACL cells compared to that of no exosome treatment group. In addition, the expression of collagen synthesis, TGFβ, VEGF, and tenogenesis gene were all significantly increased in the 8 weeks injured ACL cells after 24 h hUSC-EX delivery. Discussion: Lyophilized exosomes are easily stored and readily usable after hydration, thereby preserving their characteristic properties. Treatment with lyophilized hUSC-EX improved the activity and gene expression of 8 weeks injured ACL cells. Conclusion: Lyophilized hUSC-EX preserve the characteristics of exosomes and can improve chronically injured (8 weeks) ACL cells. Lyophilized hUSC-EX could serve as effective and safe biomaterials that are ready to use at room temperature to enhance cell activity in patients with partial ACL tears and after remnant preservation ACL reconstruction. [ABSTRACT FROM AUTHOR]

Background: Calcium silicate-based bioceramics have been applied in endodontics as advantageous materials for years, many chemical components and new synthesizing methods were used to improve the base formulation of the materials for positively affecting the sealers properties. Recently, a novel biomaterial formulation, grounded in strontium silicate, has been introduced to the market, offering potential advancements in the field. Objective: To comparatively analyze the cytotoxicity and cell migration effects of a novel strontium silicate-based bioceramic material (CRoot SP) and those of calcium silicate-based (iRoot SP) and epoxide amine resin (AH Plus) sealers on stem cells derived from rat apical papilla(rSCAPs). Methods: rSCAPs were isolated and characterized in vitro and subsequently cultured in the presence of various concentrations of CRoot SP, iRoot SP and AH Plus extracts. Cytotoxicity was assessed by CCK-8 assay, and cell-migration capacity was assessed by using wound healing assays. Results: No significant differences in cell viability were observed in the 0.02 mg/mL and 0.2 mg/mL sealer groups. The cell viability of CRoot SP was consistently greater than that of iRoot SP at concentrations of 5 mg/mL and 10 mg/mL across all time points. Maximum cytotoxic effect was noted on day 5 with 10 mg/mL AH Plus.The scratch was partly healed by cell migration in all groups at 24 h, and the 0.02 mg/mL, and 0.2 mg/mL CRoot SP exerted beneficial effects on rSCAPs migration. Conclusions: CRoot SP exhibited less cytotoxic than the iRoot SP and AH Plus extracts after setting. A lower concentration of CRoot SP thus promotes the cell migration capacity of rSCAPs, and it may achieve better tissue repair during root canal treatment. [ABSTRACT FROM AUTHOR]

Background: Medication-related osteonecrosis of the Jaw (MRONJ) is a rare but severe side effect in patients treated with medications such as Bisphosphonates (BPs). Its pathophysiological mechanism needs to be more precise. Establishing preventive measures and treatment standards is necessary. This study aimed to develop a composite hydrogel scaffold constituted by methacrylated gelatin (GelMA), methacrylated heparin (HepMA) and PRF, and investigate its potential application value in the prevention of MRONJ. Methods: GelMA, HepMA, and PRF were prepared using specific ratios for hydrogel scaffolds. Through mechanical properties and biocompatibility analysis, the release rate of growth factors and the ability to promote bone differentiation in vitro were evaluated. To explore the healing-enhancing effects of hydrogels in vivo, the composite hydrogel scaffold was implanted to the MRONJ rat model. Micro-computed tomography (Micro-CT) and histological examination were conducted to evaluate the bone morphology and tissue regeneration. Results: The Hep/GelMA-PRF hydrogel improved the degradation rate and swelling rate. It was also used to control the release rate of growth factors effectively. In vitro, the Hep/GelMA-PRF hydrogel was biocompatible and capable of reversing the inhibitory effect of zoledronic acid (ZOL) on the osteogenic differentiation of MC3T3-E1s. In vivo, the micro-CT analysis and histological evaluation demonstrated that the Hep/GelMA-PRF group exhibited the best tissue reconstruction. Moreover, compared to the ZOL group, the expression of osteogenesis proteins, including osteocalcin (OCN), type collagen I (Col I), and bone morphogenetic protein-2 (BMP-2) in the Hep/GelMA-PRF group were all significantly upregulated (P < 0.05). Conclusions: The Hep/GelMA-PRF hydrogel scaffold could effectively control the release rate of growth factors, induce osteogenic differentiation, reduce inflammation, and keep a stable microenvironment for tissue repair. It has potential application value in the prevention of MRONJ. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of staining beverages on the color-changing of resin-infiltrated artificial white spot lesions (WSLs). Methods: Thirty-five artificial WSLs were created by pH cycling on flat bovine teeth specimens. The WSLs were treated with resin infiltration and were divided into five groups based on staining beverages: artificial saliva, coffee, wine, green tea, and Coca-Cola. These specimens were subjected to a 28-day exposure to the respective beverages. Color stability was assessed using a spectrophotometer at different time points: baseline, after 7, 14, 21, and 28 days of exposure, and repolishing. The color difference (∆E) between each time point and the baseline was calculated. Statistical analysis was performed using two-way measures ANOVA with a significance level of p = 0.05. Results: All resin-infiltrated specimens exposed to staining beverages for 7 days exhibited more significant color changes than those exposed to artificial saliva. The color change patterns varied based on the type of beverage. The color alterations intensified with extended immersion in the wine and Coca-Cola groups, while there were no significant differences in the color of specimens after 28 days of immersion in the coffee and green tea groups. However, after cleaning with pumice powder, all specimens showed significantly reduced color changes compared to those observed after 28 days of immersion, except those immersed in coffee. Conclusions: Exposure of resin-infiltrated bovine tooth specimens to staining beverages resulted in a significant color alteration as the immersion time increased. However, the staining effect could be minimized by cleaning with pumice powder, except for the coffee group. Clinical relevance: After resin infiltration treatment, patients should be advised to minimize the consumption of colored beverages to prevent staining that could impact esthetic appearance. [ABSTRACT FROM AUTHOR]

Aim: This study compared the effectiveness of several techniques in restoring compromised bonding to recently bleached enamel. Methods: Seventy-five healthy bovine incisors were divided into five groups (n = 15). Fifteen teeth (Group 1) remained intact, whereas 60 (Groups 2 to 5) underwent at-home bleaching with 16% carbamide peroxide. The bonding procedures were as follows: Group 1: Bonding of resin composite to unbleached enamel; Group 2: Bonding immediately after bleaching; Group 3: Application of a 10% sodium ascorbate solution for 10 min before bonding; Group 4: Enamel removal to the depth of 0.5 mm; and Group 5: Increased curing time of the bonding agent to 80 instead of 20 s. After 24 h, the specimens were subjected to micro-shear testing, and the failure mode was determined. Results: ANOVA revealed a significant difference in bond strength among the groups (P < 0.001). The mean bond strength was significantly lower in group 2 than in other groups (P < 0.05), which showed comparable bond strength to each other (P > 0.05). Adhesive failure was the most predominant failure type in all groups. The mixed failure occurred with a frequency of 26.7% in groups 3 and 5. The Fisher's exact test revealed a significant difference in failure modes among the groups (P = 0.047). Conclusions: The three experimental procedures used in this study, including the application of 10% sodium ascorbate before bonding, enamel removal to the depth of 0.5 mm, and increasing the curing time of the bonding agent to 80 s, were effective in restoring the compromised bonding to recently bleached enamel. [ABSTRACT FROM AUTHOR]

Background: Thyroid storm (TS), a life-threatening condition that can damage multiple organs, has limited therapeutic options. Hypercytokinemia is a suggested background, but the pathological condition is unclear and there are no appropriate animal models. We aimed to develop a TS mouse model by administration of triiodothyronine and lipopolysaccharide, and then to examine the effects of ghrelin on this model. Methods: We evaluated the use of serum IL-6 levels as a representative marker of hypercytokinemia in patients with TS. To establish the mouse model, preliminary experiments were conducted to determine the non-lethal doses of triiodothyronine and lipopolysaccharide when administered individually. As a TS model, C57BL/6 mice were administered with triiodothyronine 1.0 mg/kg (subcutaneously, once daily for seven consecutive days) and lipopolysaccharide 0.5 mg/kg (intraperitoneally, on day 7) to develop a lethal model with approximately 30% survival on day 8. We assessed the survival ratio, mouse sepsis scores and blood biomarkers (IL-6, metanephrine, alanine aminotransferase) and evaluated the effects of ghrelin 300 µg/kg on these parameters in TS model. Results: Serum IL-6 was increased in patients with TS compared with those with Graves' disease as the diseased control (18.2 vs. 2.85 pg/mL, P <.05, n = 4 each). The dosage for the murine TS model was triiodothyronine 1.0 mg/kg and lipopolysaccharide 0.5 mg/kg. The TS model group had increased mouse sepsis score, serum IL-6, metanephrine and alanine aminotransferase. In this model, the ghrelin improved the survival rate to 66.7% (P <.01, vs. 0% [saline-treated group]) as well as the mouse sepsis score, and it decreased the serum IL-6 and metanephrine. Conclusion: We established an animal model of TS that exhibits pathophysiological states similar to human TS with induction of serum IL-6 and other biomarkers by administration of T3 and LPS. The results suggest the potential effectiveness of ghrelin for TS in humans. [ABSTRACT FROM AUTHOR]

Background: Acute gouty arthritis (AGA) is classified as 'arthritis' in traditional Chinese medicine (TCM) theory. Shirebi granules (SGs), derived from the classic prescription SiMiaoWan, exerts satisfying therapeutic efficacy in ameliorating AGA clinically. However, the underlying mechanisms of SGs against AGA remain unclarified. Methods: AGA-related biological processes, signal pathways and biomarker genes were mined from the GEO database through bioinformatics. SGs components were systematically recognized using the UPLC-Q-TOF–MS/MS. A correlation network was established based on the biomarker genes and the chemical components, from which the signal pathway used for further study was selected. Finally, we established an AGA model using SD rats injected with monosodium urate (MSU) in the ankle joint for experimental validation. A combination of behavioral tests, H&E, safranin O- fast green, western blotting, and immunofluorescence were employed to reveal the mechanism of action of SGs on AGA. Results: The deterioration of AGA was significantly related to the imbalance between immunity and inflammation, neutrophil chemotaxis and inflammatory factor activation. HDAC5, PRKCB, NFκB1, MPO, PRKCA, PIK3CA were identified to be the candidate targets of SGs against AGA, associated with neutrophil extracellular traps (NETs) signal pathway. Animal experiments demonstrated that SGs effectively repaired cartilage damage, blocked TLR4 activation, and inhibited the expression of NETs indicators and inflammatory factors. In addition, SGs prominently alleviated joint redness and swelling, improved joint dysfunction, inhibited inflammatory infiltration of AGA rats. Conclusion: Our data reveal that SGs may effectively alleviate the disease severity of AGA by suppressing NETs-promoted imbalance between immunity and inflammation. [ABSTRACT FROM AUTHOR]