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In order to better demonstrate the relationship between agricultural economic structure growth and environmental pollution, an autoregressive model based on time-varying parameter vector was proposed. In the process of developing the research, this paper introduces the LDMI method, based on the time-varying parameter vector autoregression model, with the help of sampling formula calculation and other methods. Efforts were made to obtain credible conclusions. The experiment result shows that in this study, a total of 10,000 samples were taken. According to this value, 10000/116.15 = 86, which means that at least 86 unrelated samples can be obtained. Therefore, we can determine that each indicator mentioned in this paper has valid samples when it is introduced into the time-varying parameter vector autoregression (TVP-VAR) model for parameter estimation. After sampling detection image analysis and data calculation, the effect of energy structure, energy intensity industrial structure, and scale effect on the emission scale of environmental pollutants was obtained. It is proved that through the research of this paper, two main conclusions are finally obtained, and the influence of the five factors mentioned above is summarized. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmunity illness, mainly featured with synovitis of the joint. The specificity of ferroptosis is disparate in different diseases, and the mechanism of ferroptosis in RA has some uncertainty yet. Therefore, the mechanism of ferroptosis was deeply observed in RA patients and animal models. In this paper, plasma of RA patients, the tumor necrosis factor-alpha-induced human synovial fibroblasts, and an animal model of arthritis induced by collagen were applied to initially inquire about the therapeutic effect of ferroptosis. For the RA patients, ELISA detected protein expression of glutathione (GSH), GPX4, Nrf2, Keap-1, and ferritin. In cell experiments, erastin or fer-1 regulated the invasion of human synovial fibroblast cells, mitochondrial membrane potential, reactive oxygen species (ROS) expression, marker protein, and so on. For the animal experiments, 32 Sprague–Dawley male rats were randomly separated into four groups with a collagen-induced RA model for 14 days and administered with erastin or fer-1 for 35 days. The expressions of GSH, GPX4, Nrf2, and Keap-1 were lower, and the ferritin was higher in RA patients, and the expressions of these proteins varied significantly after disease remission. In addition, ferroptosis inactivation also reduced the proliferation and migration ability, mitochondrial membrane potential, and ROS in cells. We discovered unexpectedly that activation of ferroptosis meaningfully forbore the foot swelling in animals with CIA, reduced arthritis scores, destruction of bone, and articular synovitis, and also decreased the high expression of inflammatory factors in plasma. There is a nonlinear relationship between human disease manifestations and animal model pathology. Ferroptosis regulating in RA for humans or animals may produce different effects. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment (TME) and play a key role in TME, participating in the process of tumor occurrence, growth, invasion, and metastasis. Among them, metastasis to tumor tissue is the key step of malignant development of tumor. In this paper, the latest progress in the role of TAMs in the formation of tumor microenvironment is summarized. It is particularly noteworthy that cell and animal experiments show that TAMs can provide a favorable microenvironment for the occurrence and development of tumors. At the same time, clinical pathological experiments show that the accumulation of TAMs in tumor is related to poor clinical efficacy. Finally, this paper discusses the feasibility of TAMs-targeted therapy as a new indirect cancer therapy. This paper provides a theoretical basis for finding a potentially effective macrophage-targeted tumor therapy. [ABSTRACT FROM AUTHOR]

In Brazil, the use of Eucalyptus is focused on the production of wood or pulp for the paper industry but without any general recovery of waste, with leaves and branches being left on the ground. One possibility is to use these residues as raw materials in the production of industrially relevant and value-added compounds such as essential oil. The aim of the present study was to investigate the chemical composition, yield, anti-inflammatory/antinociceptive activities, and acute toxicity in mice, as well as the antimicrobial effects of essential oils from the leaves of 7 varieties of Eucalyptus and hybrids against Escherichia coli, Staphylococcus aureus, and Candida albicans. The extraction of oils was carried out using hydrodistillation, and they were analyzed by gas chromatography coupled to mass spectrometry. Urocam and Grancam were the plants that obtained the highest oil yield, with yields of 3.32 and 2.30%, respectively. The main chemical components identified in these plants were 1.8 cineole and α-pinene. The antinociceptive effect of the 7 oils (50 mg/kg, p.o.) was initially assessed in the acetic acid-induced writhing test. In this assay, a significant (p < 0.05) antinociceptive/anti-inflammatory effect was observed from 4 tested essential oils (E. benthamii, E. saligna, and the hybrids Urocam and Grancam) when compared to the vehicle-treated group. This effect was then confirmed in the formalin-induced paw licking test. No toxicological effects or alterations were observed in motor coordination after the administration of the studied oils to the animals. In the antimicrobial evaluation, the seven essential oils inhibited the growth of S. aureus, E. coli, and C. albicans at different concentrations. Collectively, these results demonstrate that the essential oil from the leaves and branches of Eucalyptus species and varieties present potential biomedical applications and represent a source of antimicrobial and/or anti-inflammatory compounds. [ABSTRACT FROM AUTHOR]

Background. With the continuous advancement of clinical application and experimental research of JTP, the application prospect of JTP in nervous system diseases and metabolic diseases is becoming increasingly clear. Jiaotai Pill (JTP) is a traditional Chinese medicine formula for insomnia, consisting of Coptidis rhizoma and Cinnamomi cortex, which dates back to Han Shi Yi Tong in the Ming Dynasty of China. Objective. Based on the brain-gut axis theory, this paper aims to explore the potential mechanism of JTP in the intervention of insomnia by using intestinal microbiome and metabolomics technology, taking the animal model of insomnia as the research object, so as to provide experimental basis for its further application and research. Methods. The insomnia mouse model was induced by intraperitoneal injection of para-chlorophenylalanine (PCPA). The clinical equivalent dose of JTP was administered by gavage for one week. The efficacy of JTP was evaluated by behavioral tests, serum biochemical detection, and brain histomorphological observation. The contents of cecum were analyzed by microbiomics and metabolomics. Results. The results show that insomnia caused by PCPA led to daytime dysfunction, higher HPA axis hormone levels, and morphologically impaired hippocampus. JTP reversed these anomalies. Omics research indicates that JTP significantly reduced gut α diversity; at the phylum level, JTP reduced the relative abundance of Firmicutes, Deferribacterota, Cyanobacteria, and Actinobacteriota and increased the relative abundance of Verrucomicrobiota, Proteobacteria, and Desulfobacterota. At the genus level, JTP reduced the relative abundance of Muribaculaceae, Lachnospiraceae_NK4A136_group, Alistipes, Colidextribacter, Muribaculum, and Mucispirillum and increased the relative abundance of Bacteroides and Akkermansia. JTP also reversed the activation of the linoleic acid metabolism pathway induced by insomnia. The combined analysis of omics suggests that JTP may play a role by regulating the inflammatory state of the body. Further gene expression analysis of brain tissue confirmed this. Conclusions. We hypothesize that JTP may achieve insomnia relief by eliminating inflammation-causing bacteria in the gut and reducing inflammation levels through the brain-gut axis, pointing to potential targets and pathways for future research on JTP. [ABSTRACT FROM AUTHOR]

Background. Diabetes mellitus (DM) is a metabolic disorder characterized by a persistent rise in the blood glucose level resulting from defects in cellular insulin function, secretion, or both, which affects millions of people every year. Several drawbacks have been stated with the use of marketed antidiabetic medicines such as drug resistance, adverse effects, toxicities, and even costs. Due to these several limitations, searching for novel antidiabetic medicines from medicinal plants (MPs) is becoming an active area of research. Therefore, MPs are exemplary sources of medicines with many accessible agents being obtained from them because numerous active constituents are isolated from them for direct use as pharmacological medicines or act as lead compounds. This paper was aimed to synthesize a concluding remark using in vitro and in vivo evaluations of extracts and fractions for antidiabetic potentials in Ethiopia, which can be used to direct future clinical trials and related investigations. Method. So as to get data on the different investigations, publications related to experimental evaluations on animal diabetic models in Ethiopia were searched from databases, such as Google Scholar, Web of Science, Medline, PubMed, and Scopus using English key terms. Results. In this paper, about 37 research findings based on data from various areas of Ethiopia published until the end of November 2020 were included. A total of 37 MP species extracts and fractions belonging to 19 families have been revealed in vitro or in vivo for potential antidiabetic activities. Crude extracts were carried out mostly by hydromethanolic whereas fractions were done mostly by chloroform. Leaves were the most commonly experimentally investigated plant part. Among the MP species experimentally studied, the most frequently used to treat DM in Ethiopia were Thymus schimperi Ronniger (Lamiaceae), Moringa stenopetala (Baker f.; Moringaceae), Ajuga remota Benth (Lamiaceae), and Datura stramonium Linn. (Solanaceae). Conclusion. This paper gives aggregate evidences on the potential antidiabetic activities of MPs in Ethiopia. Antidiabetic MPs used in Ethiopia represent crucial input for the future development of novel antidiabetic drugs. To this end, more pharmacological and toxicological investigations need to be considered to prove the safety of constituents obtained from these MPs. Finally, we recommend upcoming research to ensure future success in the clinical study and development of novel medicines for DM treatment from these frequently evaluated MPs. [ABSTRACT FROM AUTHOR]

The aim of this paper was to explore the mechanism of bladder meridian massage (BMM) on anxiety in rats with chronic stress. Chronic stress induced rats to establish rat anxiety model. The sugar water preference (SPF), tail suspension time (TST), and forced swimming time (FST) of rats were measured. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines in serum and hippocampus of rats were detected. Brain neurotransmitters (dopamine (DA), 5- hydroxytryptamine (5-HT), and norepinephrine (NE)) were detected by enzyme-linked immunosorbent assay (ELISA) kits. Immunohistochemistry and western blotting were used to detect autophagy protein expression in hippocampus of rats. BMM significantly increased SPF, decreased TST and FST, increased SOD level in serum and hippocampus, and decreased MDA level and cytokine level. BMM reversed the changes of neurotransmitters. At the same time, BMM significantly decreased autophagy protein expression in hippocampus of rats. The above results show that BMM significantly relieve anxiety induced by chronic stress in rats. [ABSTRACT FROM AUTHOR]

Objective. This paper aims to explore novel ferroptosis-related biomarkers for acute kidney injury (AKI). Methods. Various bioinformatic methods, such as differential expression analysis, functional annotation analysis, machine learning, and chemical-gene network analysis, were used in this study. Furthermore, the expression and proferroptotic role of RPS7 were validated with further bioinformatics analysis and biochemical experiments. Results. GSE30718 dataset and GSE139061 dataset were used, and the differentially expressed genes (DEGs) were screened. The DEGs were overlapped with ferroptosis-related genes and genes associated with AKI, which led to the identification of four candidate genes. Machine learning and ROC curve analysis were conducted, and RPS7 and TRIB3 were selected for diagnostic model analysis and functional analysis. Finally, the upregulation of RSP7 in cisplatin-induced AKI was validated in cisplatin-induced AKI, and its proferroptotic role was confirmed in cisplatin-treated proximal tubular cells. Conclusion. Our results indicated that RPS7 might present as a novel ferroptosis-related biomarker for AKI, and it derived ferroptosis to accentuate cisplatin-induced AKI. [ABSTRACT FROM AUTHOR]

Objective. This paper intends to verify through in vivo experiments whether ginsenoside Rh2 (G-Rh2) can play an anti-inflammatory role by modulating cardiomyocyte (CM) pyroptosis in rats with acute myocardial infarction (AMI), thereby alleviating myocardial injury. Methods. Twenty SD rats were randomized into control, L-Rh2, M-Rh2, and H-Rh2 groups, among which the latter three groups were modeled for AMI and given an intraperitoneal injection of G-Rh2 (L-Rh2: 2 mg/kg; M-Rh2: 4 mg/kg; H-Rh2: 8 mg/kg), while the control group was only treated with thoracotomy and sodium chloride injection. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), left ventricular systolic pressure (LVSP), and left ventricular end-diastolic pressure (LVEDP) were recorded by ultrasonic diagnosis. Rats were killed under anesthesia, and the morphological characteristics of ventricular tissue were observed by electron microscope. Additionally, cardiac blood and ventricular tissues were collected to quantify the contents of myocardial injury markers (creatine phosphate kinase (CK), creatine phosphokinase-MB isoenzyme (CK-MB), and lactate dehydrogenase (LDH) by ELISA, as well as the expression of pyroptosis-related genes cysteinyl aspartate specific proteinase 1 (Caspase-1), gasdermin D (GSDMD), interleukin (IL)-1β, and NOD-like receptor thermal protein domain associated protein 3 (NLRP3) by qRT-PCR and Western blot). Results. Ultrasonic examination identified lower HR, SBP, DBP, MAP, and LVSP in the three Rh2 injection groups compared with the control group (P < 0.05); and in comparison with M- and H-Rh2 groups, HR, SBP, DBP, MAP, and LVSP were all lower in L-Rh2 group, while LVEDP was higher (P < 0.05). Microscopically, CMs and organelles in the L-RH2, M-RH2, and H-RH2 groups were damaged to varying degrees compared with the control group, with those in the L-RH2 group being the most serious. CK, CK-MB, and LDH were also the highest in the L-Rh2 group and the lowest in the control group, while their levels were obviously reduced in M- and H-Rh2 groups (P < 0.05). Finally, GSDMD, IL-1β, NLRP3, and Caspase-1 were found to be reduced in the control group, while pyroptosis-related gene expression in the M-Rh2 group was improved markedly (P < 0.05). Conclusion. G-Rh2 can inhibit the pathological development of AMI by relieving the focal death of CM and inhibiting the release of proinflammatory factors in the body, and the effect is significantly related to the dosage, which is expected to become a new treatment option for AMI in the future. [ABSTRACT FROM AUTHOR]

Background. In the present study, we systematically evaluated the effects of Traditional Chinese Medicine (TCM) on androgenetic alopecia (AGA) in rodent models (rats and mice) to provide potential evidence for the treatment of AGA by TCM. Methods. Previous research papers focusing on the treatment of AGA by TCM were retrieved from various electronic databases (PubMed, Embase, The Cochrane Library, CNKI, Vip, Wanfang data, and CBM) up to October 30, 2021. Screening of the literature was performed independently, and data were extracted and assessed. A meta-analysis was performed using RevMan 5.3 software. Results. When compared with the model groups, a group of C57BL/6 mice treated with TCM showed an increase in the total number of hair follicles (mean difference [MD] = 11.99, 95% confidence interval [CI] [5.94,18.03], P = 0.0001), as well as a decrease in serum testosterone (T) level (MD = −1.10, 95% CI [−1.43, −0.78], P < 0.00001), skin discoloration time (MD = −2.93, 95% CI [−4.03, −1.84], P < 0.00001), and skin hair growth time (MD = −3.16, 95% CI [−4.16, −2.16], P < 0.00001). Terminal hair/vellus hair also increased in TCM-treated AGA animals (MD = 3.02, 95% CI [2.05, 3.98], P < 0.00001). No significant difference was found in serum estradiol (E2) level, skin tissue E2 level, or skin tissue T level between the TCM-treated group and the model group. Conclusion. TCM can increase the total number of hair follicles and terminal hair/vellus hair ratio, and reduce skin discoloration time and skin hair growth time in AGA animal models. These effects may be related to the reduction of the serum T level in AGA animals. These conclusions need to be verified by high-quality studies as the current analysis may be affected by the number and quality of the studies identified. [ABSTRACT FROM AUTHOR]

This paper was designed to predict the mechanisms of the active components of Huaji Jianpi Decoction (HJJPD) against nonalcoholic fatty liver disease (NAFLD) based on network pharmacology-combined animal experiments. The candidate compounds of HJJPD and its relative targets were obtained from TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the target protein-protein interaction (PPI) and component-target-pathway networks were constructed. Moreover, gene function annotation (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to study the potential signaling pathways associated with HJJPD's effect on NAFLD. Molecular docking simulation was preformed to validate the binding affinity between potential core components and key targets. Eventually, the candidate targets, the possible pathway, and the mechanism of HJJPD were predicted by the network pharmacology-based strategy, followed by experimental validation in the NAFLD mice model treated with HJJPD. A total of 55 candidate compounds and 36 corresponding genes were identified from HJJPD that are associated with activity against NAFLD, and then the network of them was constructed. Inflammatory response and lipid metabolism-related signaling pathways were identified as the critical signaling pathways mediating the therapeutic effect of the active bioactive ingredients on NAFLD. Compared with the model group, the liver wet weight, liver/body ratio, the levels of total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and high-density lipoprotein (HDL) in serum in the HJJPD low-dose (17.52 g/kg·d), medium-dose (35.04 g/kg·d), and high-dose (70.07 g/kg·d) groups significantly decreased (P < 0.05). Light microscope observation shows that HJJPD could control the degree of lipid denaturation of the mouse liver tissue to a great extent. RT-qPCR results show that the mRNA expression levels of peroxisome proliferative activated receptor gamma (PPARG), tumor necrosis factor-α (TNF-α), antiserine/threonine protein kinase 1 (AKT1), and prostaglandin-endoperoxide synthase (PTGS2) in the liver tissues of the three HJJPD groups (17.52 g/kg·d, 35.04 g/kg·d, and 70.07 g/kg·d) were significantly lower than those in the model group (P < 0.05). HJJPD can exert its effect by inhibiting hepatic steatosis and related mRNA expression and decreasing the levels of other liver-related indexes. This study suggested that HJJPD exerted its effect on NAFLD by modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of HJJPD. [ABSTRACT FROM AUTHOR]

In recent years, the popularity of sports has been increasing. In the high-intensity competition, many players have been injured; most of them are myocardial ischemia. With the development of medical science and technology, myocardial ischemia can be reperfusion. However, sometimes, the function of tissues and organs cannot be restored, but the dysfunction and structural damage of tissues and organs can be aggravated. Therefore, it is necessary to actively carry out intermittent exercise to protect players from myocardial ischemia-reperfusion injury. The purpose of this paper is to explore the protective effect of intermittent exercise on the myocardial ischemia-reperfusion injury of players. 60 clean male Sprague Dawley (SD) old rats were selected as the research objects, which were divided into control group, ischemia/reperfusion model group, intermittent exercise + model group, and intermittent exercise + control group, and compared the parameters of heart function indexes of each group. The results showed that the creatine kinase (CK) content of control group was 0.577 ± 0.176 u / ml , lactate dehydrogenase (LDH) content was 7.834 ± 1.507 u / ml , model group was 1.257 ± 0.113 u / ml , lactate dehydrogenase (LDH) content was 14.441 ± 1.793 u / ml , intermittent exercise + model group was 0.987 ± 0.127 u / ml , lactate dehydrogenase (LDH) content was 11.714 ± 3.017 u / ml , intermittent exercise + control group was 1.103 ± 0.125 u / ml , and lactate dehydrogenase (LDH) content was 14.647 ± 2.575 u / ml. It can be seen that intermittent exercise has a good protective effect on myocardial ischemia-reperfusion injury. If the interval exercise method is integrated into the daily training of athletes, it can effectively improve the perfusion injury caused by myocardial ischemia. [ABSTRACT FROM AUTHOR]

Caerin 1.9 is a natural peptide derived from the skin secretions of the Australian tree frog (Litoria) with broad-spectrum antimicrobial and anticancer bioactivity. It improves the efficacy of a therapeutic vaccine and immune checkpoint inhibitor therapy when injected intratumorally and inhibits TC-1 tumor growth when applied topically through intact skin in a TC-1 murine tumor model. This paper investigated the pharmaceutical kinetic profile, the tissue distribution, and the acute safety investigation of Caerin 1.9 peptide in Sprague Dawley (SD) rats. The results showed that subcutaneous injection of Caerin 1.9 at 100 mg/kg is safe and does not cause mortality or organ malfunction in the recipient rats. For the consecutive injection of F3 at 10 mg/kg, the peak concentration (Cmax) of F3 displayed at 1 hr after injection in male rats was 591 ng/mL, the average drug retention time was 0.807 hr, T1/2 was 4.58 hr, and AUC0-last was 1890 h × ng/mL. In female rats, Cmax was 256 ng/mL, with an average drug retention time of 2.96 hr, T1/2 of 1.33 hr, and AUC0-last of 740 h × ng/mL. The results showed that the concentration of Caerin 1.9 in the peripheral blood peaked at 1 hour. As injected concentration increased, T1/2 extended, and Cmax, AUC0-last, and volume of distribution at a steady state all increased. After 14 days of repeated subcutaneous injection at 10.0 mg/kg, no accumulation of Caerin 1.9 in plasma was observed. The results of tissue distribution showed that the Caerin 1.9 is below the LC-MS/MS detection threshold at a minimum concentration of 40 ng/g. In conclusion, Caerin 1.9 is well tolerated in rats and could be used with current immunotherapies for better management of solid tumors and genital warts. [ABSTRACT FROM AUTHOR]

Introduction. The purpose of this paper was to study the effect of electroacupuncture (EA) on choroidal blood flow (ChBF) in a guinea pig model of lens-induced myopia (LIM). Methods. Guinea pigs were randomly divided into 4 groups: normal control (NC) group, LIM group, LIM + electroacupuncture (LIM + EA) group, and LIM + sham acupoint (LIM + sham) group. Right eyes were covered with a −6D lens to induce myopia. Meanwhile, LIM + EA group and LIM + sham group were treated with EA at acupoints Hegu (LI4) and Taiyang (EX-HN5) and sham points. Refraction, axial length (AL), choroidal thickness (ChT), vessel density of choriocapillaris (CC) and choroidal layer, and scleral collagen fiber were measured. Besides, hypoxia-inducible factor-1α (HIF-1α), matrix metalloprotein-2 (MMP-2), and tissue inhibitor metalloprotease-2 (TIMP-2) expression in sclera were detected. Results. Refraction and AL were significantly decreased and ChT and vessel density of CC were significantly increased in LIM + EA group at 2 weeks and 4 weeks (all P < 0.05) compared with LIM group. However, no significant difference of vessel density of choroidal layer was observed between LIM and LIM + EA group at 2 weeks and 4 weeks. Scleral collagen fibrils diameters were significantly increased in LIM + EA group at 4 weeks (P < 0.001) compared with LIM group. At the end of experiment, the mRNA and protein expression of HIF-1α and MMP-2 were significantly decreased (all P < 0.05) and those of TIMP-2 were increased in LIM + EA, compared with LIM. However, there were no significant differences between LIM and LIM + sham group. Conclusions. EA can improve the vessel density of choroid and then possibly improve scleral hypoxia, which may inhibit the growth of the AL in myopia guinea pig. [ABSTRACT FROM AUTHOR]

Background. Depression is a major cause of disability and most antidepressant medicines are ineffective owing to their high toxicity and numerous adverse effects. As a result, there is an urgent need to find new effective treatment methods. This paper aims to investigate the effect and mechanism of total saikosaponins (TSS) on depression-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Methods. Twenty-four male SD rats were randomly divided into 4 groups: control group, CUMS group, TSS group, and fluoxetine (Flu) group. Then, the following tests were conducted: sucrose preference test, open field test, and elevated plus maze test. Additionally, ELISA was used to detect the levels of corticosterone (CORT) and adrenocorticotropic hormone (ACTH) in the serum of the rats as well as the levels of inflammatory cytokines IL-1β, IL-6, and TNF-α in the hippocampus, and Western blot was used for measuring the expression of brain-derived neurotrophic factor (BDNF) protein and related proteins of the PI3K/AKT/NF-κB signaling pathway in the hippocampus. Results. TSS could significantly improve rat behaviors, specifically indicated by increases in sucrose preference, total movement distance, stay time in the central area, number of entries into open arms, time spent in open arms, and a decrease in stay time in the peripheral area. TSS acted to significantly reduce BDNF protein expression and increase the contents of ACTH and CORT in serum as well as the levels of IL-1β, IL-6, and TNF-α in the hippocampal tissue in rats. In addition, it was able to raise the ratios of p-PI3K/PI3K and p-AKT/AKT and decrease the ratio of p-p65/p65 in tissues, which in turn regulated the PI3K/AKT/NF-κB signaling pathway. Conclusions. TSS, through regulating PI3K/AKT/NF-κB signaling axis, can alleviate depression-like behaviors and elevate neuroendocrine hormone levels and inflammatory factor levels. [ABSTRACT FROM AUTHOR]

The present paper explores the antioxidant and antiaging properties of agar extracted from Laminaria digitata (L. digitata) on a D-galactose (D-Gal)-induced mouse model. Experimental mice were divided into four groups: group I comprised of control nontreated mice, group II comprised of D-Gal-induced mice, group III mice were treated with extracted agar after D-Gal induction, and group IV mice were given ascorbic acid as a positive control. Antioxidant enzymes and aging marker proteins declined significantly in group II, whereas they were normal in group III and group IV mice. Expressions of interleukin-1β (IL-1β) in D-Gal-induced mice were significantly enhanced in the liver and brain of the experimental mice, which were otherwise normal in agar-treated mice. Also, IL-6 levels were significantly increased in the liver and reversed in the brain of D-gal mice, while it was regularly in the agar-treated mice. The histopathological analysis of D-Gal-induced mice showed spongiosis and tangles in brain cells, increased fat and decreased collagen contents in the skin, and few dilated sinuses in the hepatic cells. The changes were under control in group III and group IV mice, suggesting the protective effects of agar extracted from L. digitata and ascorbic acid. [ABSTRACT FROM AUTHOR]

Osteoporosis is a degenerative disease that endangers human health. At present, chemical drugs used for osteoporosis have serious side effects. Therefore, it is valuable to search herbs with high safety and good curative effect in antiosteoporosis. Erzhi formula (EZF), an ancient classic compound, has been reported to have a beneficial effect in antiosteoporosis, but its mechanism is unclear. In this paper, the active compounds of EZF were found in Systems Pharmacology Database, and gene targets related to osteoporosis were obtained in GeneCards. The GO functional and KEGG pathway enrichment analysis were performed by Metascape. The network of "components-targets-signal pathway" was constructed by Cytoscape. Next, molecular docking between the active components and hub genes related to the PI3K-Akt signaling pathway was conducted by Autodock. In the verification experiment, the zebrafish induced by prednisolone (PNSL) was used to reproduce glucocorticoid-induced osteoporosis (GIOP) model, and then the reversal effects of EZF were systematically evaluated according to the behavior, skull staining area, bone mineralization area (BMA), average optical density (AOD), and cumulative optical density (COD). Finally, it was shown that 24 components in EZF could regulate 39 common gene targets to exert antiosteoporosis effect. Besides, the main regulatory mechanisms of EZF were 4 signaling pathways: PI3K-Akt, JAK-STAT, AGE-RAGE, and cancer pathway. In PI3K-Akt signaling pathway, wedelolactone, dimethyl wedelolactone, specnuezhenide, ursolic acid, acacetin, beta-sitosterol, apigenin, and kaempferol can bind tightly with EGF, IL-2, and IL-4 genes. Compared with the model group, the moving distance, swimming speed, and cumulative swimming time of zebrafish in EZF group were significantly increased (P < 0.05). Meanwhile, the BMA and COD of zebrafish were significantly improved after the intervention of EZF (P < 0.05). In summary, the 24 components of EZF exert their antiosteoporosis effects by regulating 39 related gene targets, among which the PI3K signaling pathway is crucial. EZF can promote bone formation and reversed GIOP through "multicomponent/multitarget/multipathway" and the medium dose of EZF may be the most suitable concentration for the treatment of GIOP in zebrafish model. [ABSTRACT FROM AUTHOR]

Land-use practices such as agriculture can impact mosquito vector breeding ecology, resulting in changes in disease transmission. The typical breeding habitats of Africa's second most important malaria vector Anopheles funestus are large, semipermanent water bodies, which make them potential candidates for targeted larval source management. This is a technical workflow for the integration of drone surveys and mosquito larval sampling, designed for a case study aiming to characterise An. funestus breeding sites near two villages in an agricultural setting in Côte d'Ivoire. Using satellite remote sensing data, we developed an environmentally and spatially representative sampling frame and conducted paired mosquito larvae and drone mapping surveys from June to August 2021. To categorise the drone imagery, we also developed a land cover classification scheme with classes relative to An. funestus breeding ecology. We sampled 189 potential breeding habitats, of which 119 (63%) were positive for the Anopheles genus and nine (4.8%) were positive for An. funestus. We mapped 30.42 km2 of the region of interest including all water bodies which were sampled for larvae. These data can be used to inform targeted vector control efforts, although its generalisability over a large region is limited by the fine-scale nature of this study area. This paper develops protocols for integrating drone surveys and statistically rigorous entomological sampling, which can be adjusted to collect data on vector breeding habitats in other ecological contexts. Further research using data collected in this study can enable the development of deep-learning algorithms for identifying An. funestus breeding habitats across rural agricultural landscapes in Côte d'Ivoire and the analysis of risk factors for these sites. [ABSTRACT FROM AUTHOR]

Objective. This study is aimed at evaluating the effects of Dialium guineense Willd fruit pulp powder on diarrhea induced by castor oil in Wistar rats. Materials and Methods. Three different tests were carried out. A preventive test by administration of a single dose of 250, 500, 1000, 2000, and 4000 mg/kg before the induction of diarrhea by castor oil. Another preventive test after repeated administration of Dialium guineense at 250, 500, and 1000 mg/kg/day for 8 days, before the induction of diarrhea, was done. The third test was a curative test with a single dose of 250, 500, 1000, and 2000 mg/kg after the induction of diarrhea by castor oil. Results. D. guineense fruit pulp at 1000, 2000, and 4000 mg/kg administered before the induction of diarrhea, has significantly delayed diarrhea; reduced the frequency of defecation, reduced the amount of diarrheal stools, and also reduced the purging index, with a degree of inhibition comparable to that of loperamide. But the water content of the stools of the group treated with D. guineense does not change significantly compared to the controls. D. guineense has reduced significantly from 500 mg/kg the diarrhea induced by castor oil after 8 days of treatment. It appears that the doses of 250 and 500 mg/kg, which were not effective with the single-dose preventive test, significantly delayed diarrhea; reduces the frequency of diarrheal stools and also reduces the purging index. D. guineense administered, after the induction of diarrhea, by castor oil has significantly reduced the diarrhea from 250 mg/kg. Conclusion. The fruit pulp of D. guineense has showed antidiarrheal activities in Wistar rats by reducing the frequency of defecation, the amount of diarrheal fecal matter emitted as well as the water content. It also delayed the onset of diarrhea and significantly reduced the purging index like loperamide. [ABSTRACT FROM AUTHOR]

Over 80% of cultural societies in low-income countries use plant preparations in traditional medicine with unknown potency and safety profiles. Uvariodendron anisatum root extracts are used by some Kenyan herbalists. However, the claims of the plant to remove retained placenta during birth have remained uninvestigated. Therefore, the current study evaluated its uterotonic activities. Acute toxicity in Wistar rats and the phytochemical composition of the plant were also studied. The plant was collected from Embu County in Kenya. The water and ethanol extracts were prepared by maceration. Uterine strips were isolated from primed mature female Wistar rats and used to study the uterotonic activities of the extracts. De Jalon's solution and oxytocin were used as negative and positive controls, respectively. Acute oral toxicity studies were done following the OECD 423 guideline and phytochemical screening were based on standard phytochemical procedures. The study met all the approval requirements before commencement. Data obtained from the uterotonic activity were analysed by using GraphPad Prism Version 8.0.1 software and expressed as a percentage increase or decrease of mean as mean ± SEM relative to the controls. The findings of acute oral toxicity were expressed using LD50. Additionally, the phytochemical components of the U. anisatum were tabulated. The uterotonic effect of Uvariodendron anisatum root water extract was higher than that of ethanol extract. A single dose of the Uvariodendron anisatum root water extract at 2000 mg/kg did not cause mortality in the tested Wistar rats. Besides, there were no changes in hematological and biochemical parameters. The extracts did not reveal changes in the gross morphology of the liver, kidney, heart, and lung of the tested Wistar rats. However, the histopathological studies of Uvariodendron anisatum root water extracts exhibited toxicity in the liver, kidney, and lung tissues of Wistar rats at a concentration of 2000 mg/kg. Alkaloids, glycosides, saponins, phytosterols, terpenes, proteins, phenols, and oils were recorded in Uvariodendron anisatum. The findings from this study provided scientific evidence which is useful in validating the use of Uvariodendron anisatum extracts in the stimulation of the uterus during birth. [ABSTRACT FROM AUTHOR]

Cardiometabolic diseases, including hypertension, may result from exposure to high sugar diets during critical periods of development. Here, we studied the effect of sucrose ingestion during a critical period (CP) between postnatal days 12 and 28 of the rat on blood pressure, aortic histology, vascular smooth muscle phenotype, expression of metalloproteinases 2 and 9, and vascular contractility in adult rats and compared it with those of adult rats that received sucrose for 6 months and developed metabolic syndrome (MS). Blood pressure increased to a similar level in CP and MS rats. The diameter of lumen, media, and adventitia of aortas from CP rats was decreased. Muscle fibers were discontinuous. There was a decrease in the expression of alpha-actin in CP and MS rat aortas, suggesting a change to the secretory phenotype in vascular smooth muscle. Metalloproteinases 2 and 9 were decreased in CP and MS rats, suggesting that phenotype remains in an altered steady stationary state with little interchange of the vessel matrix. Aortic contraction to norepinephrine did not change, but aortic relaxation was diminished in CP and MS aortas. In conclusion, high sugar diets during the CP increase predisposition to hypertension in adults. [ABSTRACT FROM AUTHOR]

Introduction. To investigate the effects of acupuncture on endogenous metabolites in the liver of type 2 diabetes mellitus (T2DM) with nonalcoholic fatty liver disease (NAFLD) mice-based metabolomics. Methods. Proton nuclear magnetic resonance (1H-NMR) metabolomics combined with multivariate statistical analysis and univariate analysis were used to analyze the changes of endogenous metabolites in the liver of mice in each group and to provide new clinical ideas for acupuncture in the treatment of glycolipid metabolism disorders caused by T2DM and NAFLD. Results. After 4 weeks of continuous treatment, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), and triglyceride (TG) decreased significantly in mice in the acupuncture treatment group (ATG), and the content of liver glycogen increased significantly. Based on 1H-NMR metabolomic analysis, a total of 47 metabolites were identified in the liver of T2DM with NAFLD mice, of which eight metabolites: UDP-N-acetylglucosamine, adenosine, glutamate, isoleucine, ATP, 3-hydroxybutyric acid, NADP+, and leucine were significantly altered by acupuncture treatment. Through the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, it is found that acupuncture has an intervention effect on five metabolic pathways, mainly involving amino acid metabolism, energy metabolism, and oxidative stress. Conclusion. Our study shows that acupuncture can regulate the liver metabolism mode of T2DM in NAFLD mice. It can reduce blood glucose and lipid accumulation in the liver, and these findings provide a new idea and theoretical basis for acupuncture in the treatment of diseases related to glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background. Premature infants are exposed to numerous stressors in neonatal intensive care unit (NICU) during a crucial period for brain development; this period exerts long-term influences on cognitive and behavioral development. Aims. To evaluate the effect of NICU-related stress on neonatal rat pups and explore the effect of Chinese medicine treatment (CMT). Methods. Sixty male rat pups were randomly assigned to three groups: the control group, the NICU group (NICU-related stress), and the CMT group (NICU-related stress plus CMT). All stressors and interventions were administered from 0 to 7 days after birth. Body weight, serum corticosterone levels, and behavior in the open field (OF) test, elevated plus maze (EPM) test, sucrose preference test, and Morris water maze (MWM) test were recorded, and blood samples were collected at five different time points (T0, T1, T2, T3, and T4). Results. The body weights of rats in the CMT and control groups were heavier than those in the NICU group in both early life and adulthood (P < 0.05). Serum corticosterone levels significantly differed with time (except T0 vs. T1 and T3 vs. T4) but did not significantly differ among the three groups (F = 0.441 , P = 0.894). Regardless of age, spatial memory and anxiety-like and depression-like behavior did not differ among the three groups. Conclusion. NICU-related stress exerted a long-term effect on rat growth and development but did not affect spatial memory, anxiety-like behavior, depression-like behavior, or serum corticosterone levels. CMT alleviated the impact of NICU-related stress on rats and promoted the growth and development of neonatal rats. [ABSTRACT FROM AUTHOR]

Objective. This study was to construct a ceRNA (lncRNA-miRNA-mRNA) regulatory network for prostate cancer (PCa) and to explore the prognostic correlation, key biological functions, and pathways of core RNAs. Methods. Three subgene expression matrices (miRNA, lncRNA, and mRNA expression matrix) were taken from the TCGA database and used in this investigation. Differential expression analysis and differential expression miRNAs were carried out. Next, the ceRNA (lncRNA-miRNA-mRNA) regulatory complex was used to visualize our data and show how they interacted. Ultimately, the primary molecular roles and biological pathways of PCa were identified using enrichment analysis by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). An effect of AC016773.1 on prostate cancer cell proliferation was investigated by knocking out AC016773.1 in an animal model. The interrelationship between AC016773.1 and hsa-mir-25 was validated using RNA immunoprecipitation technology. Results. The lncRNA, miRNA, and mRNA expression matrices obtained from the TCGA database contain 16901, 1881, and 19962 transcripts, respectively. Through differential expression analysis, we obtained 2010 de lncRNA comparative information, 75 lncRNA and miRNA interaction pairs, and 31 targeted de mRNAs. Through the differential expression analysis of RNA nodes in the ceRNA regulatory network, we found that compared with the NP group, in the PCa group, there were 14 lncRNAs upregulated and 25 lncRNAs downregulated, 1 miRNA upregulated and 3 miRNA downregulated, and 10 mRNA upregulated and 21 mRNA downregulated. In KEGG enrichment analysis, the pathways identified by targeted DE-mRNAs were mainly related to calcium signaling pathway, EGFR tyrosine kinase inhibitor resistance, melanoma, PI3K−Akt signaling pathway, and proteoglycans in cancer. In animal models, it was found that knocking down AC016773.1 significantly reduced tumor volume and weight, indicating that AC016773.1 may promote the proliferation of PCa cells. The use of RNA immunoprecipitation technology indicates a direct binding between AC016773.1 and hsa-mir-25. Conclusion. We elucidated the network regulatory relationship of lncRNA-miRNA-mRNA in PCa and further explored the key molecular functions, biological pathways, and prognostic value of targeted DE-mRNAs. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) have been the major cause of mortality all around the globe. Lespedeza cuneata abbreviated as L. cuneata with the authority name of Dumont de Courset (G. Don) is a perennial flowering plant commonly grown in Asian countries such as Korea, Japan, China, and Taiwan. We aimed to investigate the L. cuneata extract's antiplatelet and antithrombotic properties as GC-MS analysis indicated that the extract contained short-chain fatty acids, which have been reported to possess beneficial cardiovascular effects. L. cuneata was extracted using water, 50% EtOH, 70% EtOH, and 100% EtOH. For in vitro antiplatelet analysis, washed platelets were prepared and incubated with L. cuneata with 200 μg/mL of 50% EtOH in the presence of 1 mM of CaCl2 for 1 minute followed by agonist (collagen 2.5 μg/mL or ADP 10 μM or thrombin 0.1 U/mL) stimulation for 5 minutes over light transmission aggregometer. Scanning electron microscopy was performed to assess platelet shape change. ATP release and intracellular calcium mobilization were quantified to assess the granular content. Fibrinogen-binding assay and clot retraction assay assessed integrin αIIbβ3-mediated inside-out and outside-in signaling. Protein phosphorylation expression was investigated by western blot analysis. Finally, the in vivo antithrombotic efficacy was investigated by oral dosage of L. cuneata 200 and 400 mg/kg and aspirin 100 mg/kg for 7 days, and tail bleeding and FeCl3-induced murine thrombus model were performed. In vitro platelet aggregation and platelet shape change were dose-dependently suppressed by L. cuneata. Calcium mobilization, dense granules secretion, integrin αIIbβ3-mediated inside-out and outside-in signaling, and protein phosphorylation of MAPK and PI3K/Akt pathways were significantly inhibited. In vivo assays revealed that L. cuneata prevents side effects of synthetic drugs via nonsignificantly increasing bleeding time and improving coronary artery blood flow and animal survival. Our results demonstrate that L. cuneata exhibited potent antiplatelet and antithrombotic effects and can be considered a potential herbal medicine with cardioprotective effects. [ABSTRACT FROM AUTHOR]

Inflammatory and antimicrobial diseases constitute a major burden for society, and fighting them is a WHO strategic priority. Most of the treatments available to fight inflammatory diseases are anti-inflammatory drugs, such as corticosteroids or immunomodulators that lack cellular specificity and lead to numerous side effects. In addition to suppressing undesired inflammation and reducing disease progression, these drugs lessen the immune system protective functions. Furthermore, treating infectious diseases is more and more challenging due to the rise of microbial resistance to antimicrobial drugs. Thus, controlling the inflammatory process locally without compromising the ability to combat infections is an essential feature in the treatment of inflammatory diseases. We isolated three forms (DRS-DA2N, DRS-DA2NE, and DRS-DA2NEQ) of the same peptide, DRS-DA2, which belongs to the dermaseptin family, from the Mexican tree frog Pachymedusa dacnicolor. Interestingly, DRS-DA2N and DRS-DA2NEQ exhibit a dual activity by inducing the death of leukocytes as well as that of Gram-negative and Gram-positive bacteria, including multiresistant strains, without affecting other cells such as epithelial cells or erythrocytes. We showed that the death of both immune cells and bacteria is induced rapidly by DRS-DA2 and that the membrane is permeabilized, leading to the loss of membrane integrity. We also validated the capacity of DRS-DA2 to regulate the pool of inflammatory cells in vivo in a mouse model of noninfectious peritonitis. After the induction of peritonitis, a local injection of DRS-DA2N could decrease the number of inflammatory cells locally in the peritoneal cavity without inducing a systemic effect, as no changes in the number of inflammatory cells could be detected in blood or in the bone marrow. Collectively, these data suggest that this peptide could be a promising tool in the treatment of inflammatory diseases, such as inflammatory skin diseases, as it could reduce the number of inflammatory cells locally without suppressing the ability to combat infections. [ABSTRACT FROM AUTHOR]

Background. Catheter ablation failure poses a clinical challenge for epicardial or intramural ventricular arrhythmia (VA); however, guidewire ablation within the coronary venous system (CVS) may be effective and safe for targeting VAs. Methods. The ex vivo phase included four steps. In step 1, the steam pop incidence rates during guidewire ablation at power settings of 5, 10, 15, 20, and 25 W were analyzed using 10 mm- and 20 mm-tip guidewires. In step 2, guidewire ablation was performed for application durations of 10, 20, 30, 40, 50, 60, and 90 s, and the lesion size was measured. In step 3, the effects of saline infusion (0, 1, 2, 3, and 4 mL/min) on lesion dimensions and steam pop formation were examined. In step 4, an orthogonal array was constructed to obtain the optimal guidewire ablation parameters. In the in vivo phase, guidewire ablation within the CVS was performed in three dogs, and the lesion features in 10 days after ablation were observed. Results. In step 1, the steam pop incidence rates at 5, 10, 15, 20, and 25 W were 0%, 0%, 12.5%, 62.5%, and 100% using the 10 mm-tip guidewires and 0%, 0%, 0%, 25%, and 75% using the 20 mm-tip guidewires, respectively. In step 2, we found that the lesion areas increased with an increase in the ablation duration (the maximum lesion diameters at 30, 60, and 90 s were 4.9 ± 0.4, 7.0 ± 0.8, and 9.2 ± 0.7 mm in the 10 mm group and 3.2 ± 0.5, 4.5 ± 0.4, and 5.3 ± 0.7 mm in the 20 mm-tip group, respectively). In step 3, we observed that saline infusion was negatively correlated with ablation lesions but had a lower risk of steam pop. The optimal parameters for the 20 mm-tip guidewire ablation were 15 W, 50 s, and 2 mL/min or 20 W, 70 s, and 2 mL/min. In the in vivo phase, effective ablation lesions with maximum and minimum diameters of 3.2 ± 0.3 and 2.8 ± 0.5 mm, respectively, were created by the guidewires during the 10-day observation period after ablation. Conclusion. This novel radiofrequency guidewire ablation technique can feasibly create effective lesions within the CVS, which may improve the efficacy of catheter ablation for challenging epicardial or intramural VA. [ABSTRACT FROM AUTHOR]

Background. Traditional herbal medicine practitioners in the Ashanti region of Ghana use the fruit peels of Citrus limon (L.) Osbeck (C. limon) in preventive and curative treatment of many cancers including liver cancer. This ethnobotanical claim remains to be verified scientifically. Aim of the Study. This study investigated prophylactic hepatoprotective and anti-HCC effects of C. limon peel extract (LPE) in CCl4/olive oil-induced HCC-like rats. Materials and Methods. After preparation of LPE, it was subjected to phytochemical screening using standard phytochemical methods. A total of 30 healthy adult male Sprague-Dawley rats (weighing 150-200 g) were randomly assigned into six groups of 5 rats each. Rats in the control group received olive oil (5 mL/kg ip) twice weekly for 16 weeks. Rats in the model group received CCl4/olive oil (2 mL/kg, ip) twice weekly for 16 weeks. Rats in capecitabine (10 mg/kg po) and LPE (50, 100, and 200 mg/kg po) groups received CCl4/olive oil (2 mL/kg, i.p) in the morning and their respective treatments in the afternoon twice a week for 16 weeks. Rats in all groups had free access to food and water ad libitum. Body weight and survival rates were monitored. Rats were sacrificed under deep anesthesia, blood was collected, and liver and other organs were isolated. Aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), prothrombin time, bilirubin, C-reactive protein (CRP), alpha- (α-) fetoprotein (AFP), and liver histology were assessed. Results. Alkaloids, tannins, flavonoids, terpenoids, and saponins were detected in LPE. Model rats demonstrated increased serum levels of AFP, CRP, ALP, GGT, ALT, and AST, prothrombin time, total bilirubin, direct bilirubin, blood lymphocyte, and monocyte counts, but decreased serum albumin and total protein compared to control rats. Unlike the control, model rats demonstrated fat accumulation in periportal and centrilobular hepatocytes and neoplastic transformation. Semiquantitation of periodic acid Schiff- (PAS-) stained liver sections showed decreased glycogen storage in hepatocytes of model rats compared to control rats. Compared to the model, LPE treatment protected against CCl4-induced hepatocarcinogenesis, which was evidenced by decreased AFP, CRP, liver enzymes, total and direct bilirubin, prothrombin time, and blood lymphocyte and monocyte counts; attenuation of fat accumulation; and increased glycogen storage, albumin, and total protein. Conclusion. LPE abates CCl4-induced hepatocarcinogenesis by attenuating liver inflammation and improving metabolic, biosynthetic, and detoxification functions of the liver. The prophylactic hepatoprotective and anti-hepatocarcinogenic effects of LPE are attributable to its phytochemical composition raising hopes of finding potential anticancer bioactive compounds from C. limon fruit peels. [ABSTRACT FROM AUTHOR]

Sida cordifolia has been used to treat malaria in Ghana albeit without scientific evidence of antimalarial activity and safety. This work aimed to assess the antimalarial properties and acute toxicity of the aqueous leaf extract of S. cordifolia in murine models. Aqueous extract of the plant was analysed for both suppressive and curative antimalarial properties in chloroquine-sensitive ANKA strains of rodent Plasmodium berghei-infected mice. Acute toxicity evaluation was performed in rats according to the OECD 425 guidelines. The extract displayed antiplasmodial activity in vivo with ED50 of 117.49 ± 15.22 mg/kg and 144.84 ± 18.17 mg/kg in suppressive and curative studies, respectively. The highest % parasitaemia suppression exerted was 76.90 ± 0.64% and 61.50 ± 0.97%, respectively, in the suppressive and curative studies. Survival of infected mice treated with the extract was significantly prolonged. This was dependent on the dose of the extract but imperfectly related to the % parasitaemia suppression. Related antimalarial parameters including percentage hematocrit, changes in body weight, and temperature of experimental mice indicated alleviation of malarial symptoms of treated animals. The extract did not show toxicity in rats. Sida cordifolia L. has antimalarial properties, and was safe. It suppressed parasitaemia in both suppressive and curative studies, was not toxic to animals and prolonged the life of infected animals under treatment. This, therefore, justifies the traditional use of S. cordifolia for the treatment of malaria in Ghana. [ABSTRACT FROM AUTHOR]

The Barnes maze, a well-known spatial-learning paradigm, is based on the innate fear of rodents of large open spaces and their drive to hide. However, additional aversive stimuli (strong light and threatening sounds) are often necessary to provoke the hiding response while rendering the method cumbersome and more stressful. Our objective was to establish a Barnes maze-learning paradigm in mice using palatable food as a reward. After habituating male C57BL6/J or NMRI mice to the reward, the experimenter and the apparatus, either a slow (2 trials/day) or a massive conditioning schedule (4 trials/day), was run. Acquisition training was carried out until mice could locate the reward box with a maximum of one hole error. Then, the box was replaced to another location (reversal phase). Mice needed to relearn the new position with the same criterion. One week later, retention trials were performed. Both strains could reach the learning criteria; in the massive training within a shorter period. Spatial memory was demonstrated in the reversal and retention trials. Our results show that palatable food can be used as an efficient motivator to acquire allocentric navigation in the Barnes maze with the additional advantage of being less stressful. [ABSTRACT FROM AUTHOR]

Peganum harmala L. and Lavandula angustifolia are two traditional herbs with probable antiseizure effects. This study evaluated the effects of these two herbal extracts on pentylenetetrazol- (PTZ-) induced seizures in mice. We prepared hydroalcoholic extracts using P. harmala seeds and the aerial parts of L. angustifolia and then randomly divided 190 mice into 19 groups. Normal saline (10 mg/kg), diazepam (2 mg/kg), P. harmala (2.5, 5, 10, 15, 30, 45, and 60 mg/kg), and L. angustifolia (200, 400, 600, and 800 mg/kg) were intraperitoneally (IP) administrated 30 min before an IP administration of PTZ (90 mg/kg). Animals were observed for behavioral changes for one hour. In addition, the effects of flumazenil and naloxone on the antiseizure activity of P. harmala and L. angustifolia were assessed. P. harmala showed antiseizure activity at the dose of 10 mg/kg; it prolonged the seizure latency and decreased the seizure duration. The mortality protection rate was 90% for this herbal extract. L. angustifolia (600 mg/kg) prolonged the seizure latency and decreased both seizure duration and mortality. Neither flumazenil nor naloxone significantly reversed the antiseizure activities of P. harmala and L. angustifolia. In mice, the hydroalcoholic extracts of P. harmala and L. angustifolia showed antiseizure activity against PTZ-induced seizures. We could not delineate the exact antiseizure mechanisms of these extracts in the current study. [ABSTRACT FROM AUTHOR]

Doxorubicin-induced cardiomyopathy (DICM) is associated with a poor prognosis, and effective therapeutic drug candidates have yet to be identified. Furthermore, whether basic animal models reflect the clinical pathogenesis of DICM should be carefully examined. Although the exact mechanisms underlying the development of DICM are complex and remain unclear, oxidative stress is strongly implicated as a contributing factor. Therefore, we investigated the effects of ginseng (the root of Panax ginseng: Gin), an inexpensive and safe drug with antioxidant properties. We previously conducted a meta-analysis that yielded results suggesting its efficacy in humans. However, this study did not examine the efficacy of ginseng in detail. Therefore, this study investigated the efficacy of red ginseng (steamed and dried ginseng cultivated for over six years; RGin) in a mouse model of chronic DICM to elucidate its potential therapeutic benefits. RGin prevented the decrease in left ventricular ejection fraction associated with doxorubicin (DXR) administration and prolonged survival in DBA/2 mice. In addition, RGin reduced DXR-induced cardiomyocyte damage. These findings highlight its potential as a therapeutic option for the treatment of DICM. [ABSTRACT FROM AUTHOR]

What Is Known and Objective. Novel coronavirus disease (COVID-19) is still ravaging globally since its first discovery in 2019. With the continuous emergence of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) mutant strains, therapeutic entities are still needed to be discovered. This study was to explore SARS-CoV-2 inhibitors and therapeutic entities for COVID-19. Methods. Based on Lipinski's rule of 5, a small-scale "old" drug database (clinical drugs being used in Ordos Central Hospital) was established, and in silico screening of Mpro inhibitors was conducted. Binding affinity and interaction as well as structure-affinity relationship were analyzed. Furthermore, molecular dynamic (MD) simulation of the selected drugs was performed to understand the conformational changes in docked complex. In vitro Mpro inhibition tests were performed according to established methods. Finally, literature review of potential "old" drug for the treatment of COVID-19 was conducted. Results and Discussion. The antibiotic minocycline, an inhibitor of bacterial ribosomal RNA, was screened out which showed the highest binding affinity (−9.6 kcal/mol). Beside the hydrogen bond with Cys145 and hydrophobic interactions, minocycline formed a pi-cation with His41, which strongly supported minocycline as a Michael addition acceptor to bind with the catalytic site of Mpro. MD simulation results show that minocycline displayed less conformational changes. The structure-affinity relationship was summarized based on minocycline analogs, and minocycline showed in vitro Mpro inhibitory activity with IC50 of 5 mM. More importantly, the literature review found that minocycline had both in vitro and in vivo broad-spectrum antiviral as well as anti-inflammatory activities, and the levels of a broad spectrum of biological markers during minocycline administration were opposed to those of COVID-19 conditions (both severe and nonsevere). What is New and Conclusion. Minocycline deserves an adjunctive therapeutic option for COVID-19 condition (both severe and nonsevere). This study shed a new light on drug-repurposing strategy for the viral disease. [ABSTRACT FROM AUTHOR]

The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance. [ABSTRACT FROM AUTHOR]

Background. Podocarpus gracilis is an evergreen, dioecious tree found in Ethiopia and other African nations. It can reach a height of 60 meters. Without any scientific validation, ethnobotanical studies conducted in Ethiopia revealed that the Podocarpus gracilis plant's leaf is consumed orally to treat diabetes mellitus. Hence, this study aims to evaluate the in vivo blood glucose level lowering, lipid-lowering, and in vitro-free radical scavenging responses of Podocarpus gracilis leaf extract and fractions on experimental mice induced with diabetes. Methods. The in vitro antioxidant activity of PGC (Podocarpus gracilis) leaf extract was assessed by using a diphenyl-2-picrylhydrazyl (DPPH) assay. The oral glucose-loaded, normoglycemic, and streptozotocin- (STZ-) induced diabetic mouse models were employed. In the STZ-induced mice model, the leaf extract and solvent fractions activity on serum lipid and weight were also measured. The extract and fractions were tested at 100, 200, and 400 mg/kg dosages. One-way ANOVA was used to determine the statistical significance of BGL (blood glucose level) changes within and between groups, and Tukey's post hoc multiple comparisons were then performed. Results. In the acute toxicity study of Podocarpus gracilis leaf extract and fractions, there was no evidence of animal mortality at the maximum dose of 2 g/kg during the observation period. The extract-treated group with normoglycemia revealed a significant lowering in BGL at the 4-hour mark of 27.4% (p < 0.001) and 25.2% (p < 0.01) at doses of 200 mg/kg and 400 mg/kg, respectively, compared to that in negative control. In the oral glucose tolerance test (OGTT) model, only 400 mg/kg treated groups at 120 min after exposure showed a BGL reduction of 31.17% which was statistically significant (p < 0.05) in comparison to the negative control. In the single-dose STZ-induced model, eighth-hour BGL measurements from CE 100, CE 200, CE 400, and GLC5 showed drops in BGL of 43.1%, 44.1%, 45%, and 47.3% from baseline fasting BGL values. In the repeated streptozotocin (STZ)-induced model, at all doses of leaf extract and fractions, the fasting BGL was significantly (p < 0.001) reduced. Moreover, the leaf extract and solvent fractions have shown a significant (p < 0.001) reduction of serum lipids such as LDL, TC, and VLDL, and at the same time, it increases HDL at 14 days with body weight gained. In the test for antioxidant activity, the half-maximal inhibitory concentrations (IC50) for leaf extract and the standard medication (ascorbic acid) were 8.2 μg/ml and 3.3 μg/ml, respectively. The IC50 value denotes the concentration of the sample required to scavenge 50% DPPH radicals. Conclusion. The 80% hydromethanolic leaf extract and fractions of Podocarpus gracilis exhibited blood glucose lowering, lipid-lowering activity in normoglycemic, oral glucose tolerance test (OGTT) mode, and STZ-induced diabetic mice with weight gains. There is scientific support for the alleged traditional use as an antidiabetic, lipid-lowering, and antioxidant activity. The results need to be confirmed by future studies. [ABSTRACT FROM AUTHOR]

Small ruminants, particularly goats and sheep, are key livestock species in Mozambique, and their production is mainly undertaken by families. However, small ruminants are often plagued by diseases that can cause considerable economic damage. In this context, traditional remedies, including various plant species, have been widely used to manage these diseases. The aim of this study was to explore the use of plant-based remedies and other treatments for managing diseases in small ruminants in Maputo Province, Mozambique. Data collection involved conducting interviews with 44 small ruminant breeders across 5 districts in Maputo Province to identify the plants and other remedies commonly used for managing diseases in their animals. We identified a total of 38 plant species belonging to 22 families. Among these plants, four were not identified by their scientific name. The most important plants reported were Cissus quadrangularis, Euphorbia kirkii, and Aloe sp., with Cissus quadrangularis being particularly noteworthy as it was frequently cited for the treatment of wounds. The most commonly cited botanical families were Fabaceae, Euphorbiaceae, and Asphodelaceae. Interestingly, in addition to plant-based remedies, we also identified other nonplant sources of treatment, such as alkaline batteries, which are commonly used to treat wounds in small ruminants. The use of plants for ethnoveterinary purposes remains prevalent in Maputo province, with older breeders serving as the primary custodians of this traditional knowledge. Efforts should be made to document and share the knowledge of these older breeders, ensuring that it is not lost over time. This preservation of ethnoveterinary knowledge can contribute to sustainable livestock management and support the wellbeing of both rural communities and their animals. [ABSTRACT FROM AUTHOR]

Background. Angelica Yinzi (AYZ) is a Chinese traditional herbal formula reported to attenuate itches and inflammation caused by atopic dermatitis (AD). However, the underlying mechanism of AYZ in the attenuation of itchiness and inflammation remains unknown. Objective. This study investigated the mechanism of AYZ in reducing itchiness in mice with 1-chloro-2,4-dinitrobenzene- (DNCB-)-induced atopic dermatitis. Methods. Hematoxylin and eosin (H&E) and toluidine blue staining were used to evaluate pathological changes in skin tissue, while an enzyme‐linked immunosorbent assay (ELISA) was used to assess the cytokine levels in the skin. After that, qRT-PCR was performed to determine the mRNA levels of cytokines in the skin. Immunofluorescence and western blotting analysis were further used to assess µ-opioid receptor (MOR) expression and immunohistochemistry to assess the p-ERK, p-AKT, and κ-opioid receptor (KOR). Results. The AYZ treatment alleviated the AD clinical symptoms, including decreasing the scratching frequency, the ear thickness, and the infiltration of mast cells, lymphocytes, inflammatory cells, and mononuclear cells. In addition, AYZ inhibited the expression of interleukin (IL)-13, thymic stromal lymphopoietin (TSLP), and reduced neuraminidase (NA), corticotropin-releasing factor (CRF), and reactive oxygen species (ROS) expression. Markers involved in itches, such as p-ERK and p-AKT, were significantly downregulated following AYZ treatment. Besides, AYZ significantly increased MOR expression and downregulated KOR in the epidermis and spinal cord. Conclusion. Our findings imply that AYZ ameliorates pruritus-related AD through skin repair, antioxidation, and balancing peripheral MOR and KOR. The findings in this study lay a theoretical foundation for the control mechanism of peripheral itch. [ABSTRACT FROM AUTHOR]

Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group (P < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting. [ABSTRACT FROM AUTHOR]

Background. Type 2 diabetes mellitus increases the risk of sarcopenia, which is characterized by decreased muscle mass, strength, and function. However, there are no effective drugs to treat diabetic sarcopenia, and its underlying mechanism remains unknown. Here, we aimed to determine whether the GLP-1 receptor agonist (GLP-1RA) dulaglutide (Dul) affects the progression of diabetic sarcopenia. Methods. db/db mice were injected intraperitoneally with 0.6 mg/kg dulaglutide for 10 weeks. Mouse muscle tissues were then pathologically evaluated and stained with F4/80 or MPO to detect macrophages and neutrophils, respectively. In addition, inflammatory factors and FNDC5 in the muscle tissues were detected using qRT-PCR. Moreover, C2C12 cells were induced to enable their differentiation into skeletal muscle cells, and muscle factor levels were then detected. Furthermore, changes in muscle factor levels were detected at various glucose concentrations (11 mM, 22 mM, and 44 mM). Results. In vivo, dulaglutide alleviated muscle tissue injury; reduced levels of the inflammatory factors, IL-1β, IL-6, CCL2, and CXCL1; and reversed the level of FNDC5 in the muscle tissues of db/db mice. In vitro, a C2C12 cell differentiation model was established through the observation of cell morphology and determination of myokine levels. Upon stimulation with high glucose, the differentiation of C2C12 cells was inhibited. Dulaglutide improved this inhibitory state by upregulating the levels of both FNDC5 mRNA and protein. Conclusions. Treatment with the GLP-1RA dulaglutide protects db/db mice against skeletal muscle injury by inhibiting inflammation and regulating the differentiation of myoblasts. High glucose inhibited the differentiation of C2C12 cells and decreased the mRNA and protein levels of myokines. Dulaglutide could reverse the differentiation state induced in C2C12 cells by high glucose. [ABSTRACT FROM AUTHOR]

Objective. Crataeva nurvala is a medicinal plant, which contains a wide range of polyphenolic and bioactive compounds. The aim of the study was to evaluate the renal-protective activity of Crataeva nurvala in two-kidney, one-clip (2K1C) rats. Methods. In this study, the ethanol extract of Crataeva nurvala bark at a dose of 100 mg/kg was orally used to treat 2K1C rats for four weeks. At the end of the experiment, all rats were sacrificed and tissue samples were collected for further biochemical and histological assessments. Results. This investigation showed that Crataeva nurvala treatment prevented the kidney dysfunction in 2K1C rats. Uric acid and creatinine concentration and CK-MB activities increased in 2K1C rats which were normalized by Crataeva nurvala. 2K1C rats also showed increased oxidative stress, depicted by the elevated level of MDA, NO, and APOP in plasma and tissues. Oxidative stress parameters declined in 2K1C rats by the treatment of Crataeva nurvala. These results could be attributed to the restoration of antioxidant enzyme activities such as catalase and SOD. Crataeva nurvala extracts also upregulated antioxidant gene expression in the kidneys of 2K1C rats. Moreover, several anti-inflammatory genes were suppressed by Crataeva nurvala treatment in 2K1C rats. Furthermore, fibrosis and collagen deposition in the kidneys were also lowered by the treatment of the Crataeva nurvala extract. Conclusion. The experimental data suggest that the Crataeva nurvala extract protected renal damage and oxidative stress, probably by restoring antioxidant enzymes activities in 2K1C rats. [ABSTRACT FROM AUTHOR]

Background. Emergence of Plasmodium resistance to antimalarial drugs presents a major drawback in efforts to control malaria. To address this problem, there is an urgent and continuous need for the development of new and effective antimalarial agents. Senna occidentalis (L.) link extract has exhibited in vitro antiplasmodial activity in many pharmacological studies. To our knowledge, data on its in vivo antimalarial efficacy is still very limited. A recent study demonstrated that polar extracts from the plant roots inhibit Plasmodium berghei proliferation in a mouse model. This study further describes the efficacy and safety of a methanolic root extract of the plant as an antimalarial agent by demonstrating its effect on hematological, biochemical, and histological parameters of Plasmodium berghei-infected BALB/c mice. Methods. Rane's test, a curative approach, was used to evaluate the antimalarial efficacy of Senna occidentalis methanolic root extract in Plasmodium berghei-infected BALB/c mice. The effect of the extract on both hematological and biochemical parameters was evaluated using automated analyzers. Kidney, liver, lung, spleen, and brain tissues were harvested from euthanized mice and examined for changes in organ architecture. Results. This study demonstrates that methanolic root extract of Senna occidentalis significantly inhibited Plasmodium berghei parasitemia in BALB/c mice (p < 0.01). Infected mice that were treated with the extract depicted a significantly low level of total leucocytes (p < 0.01), red blood cell distribution width (p < 0.01), and a significantly high hemoglobin concentration (p < 0.001) compared to the infected animals that were administered with the vehicle only. The infected animals that were treated with the extract exhibited a significantly low level of urea, creatinine, bilirubin, and alkaline phosphatase (p < 0.05), compared to the infected animals that were given the vehicle only. The level of sodium, potassium and chloride ions, lymphocytes, granulocytes, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration, total protein, albumin, aspartate aminotransferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total platelets, mean platelet volume (MPV), and platelet distribution width of the infected animals treated with the extract was not significantly different from those of the infected animals that were given the vehicle only (p > 0.05). The extract alleviated organ pathological changes in the infected mice. The extract did not induce any remarkable adverse effect on the growth, hematological, and biochemical parameters of uninfected animals (p > 0.05). In addition, administration of the extract did not alter the gross appearance and histological architecture of the organs, implying that the extract was well tolerated in mice. Conclusions. Senna occidentalis methanolic root extract exhibited good antimalarial activity against Plasmodium berghei and may be safe in mice. [ABSTRACT FROM AUTHOR]

Background. Diabetes impacts various organs in the body and some reports showed that the lung is also affected by diabetes, and an imbalance of inflammation and oxidative stress may participate to diabetic lung impairments. The present study is conducted to assess the impacts of Citrullus colocynthis (CC) on some aspects of these impairments. Methods. Frothy two male Wistar rats (3-4 months old and weighing 200–250 g) were used in the present research. Animals were divided into 3 groups of control, Diabetes, and Diabetes + Drug. CC was administered to diabetic rats orally. The lung tissue and BALF oxidative stress and inflammatory indices including the MDA, TAC, SOD, Gpx, TNFα, IL-6, IL-17, and IL-10 were evaluated by the ELISA method. Results. Our observations disclosed the ameliorative impacts of CC administration against oxidative stress and inflammation imbalance. Also, it was found that CC improved body weight and fasting blood sugar in rats with diabetes. Conclusion. We can conclude that the administration of CC can be effective in improving diabetic lungs in rats. [ABSTRACT FROM AUTHOR]

Background. Olea europaea leaf extract (OELE) has potential health benefits and protects against cytotoxicity. This study investigated the possible ameliorative effect of OELE on cisplatin-induced nephrotoxicity in rats. Methods. Rats were assigned into six groups; two groups received 150 mg/kg or 300 mg/kg of OELE, one group received a single dose of cisplatin (6 mg/kg) IP on the first day of the experiment, two groups received a single dose of cisplatin 150 mg/kg or 300 mg/kg of OELE on the first day then starting from the fifth day for 10 consecutive days, and one group acted as a control. Results and Conclusion. The findings showed that cisplatin-induced nephrotoxicity was evidenced by a significant increase in serum creatinine blood urea nitrogen (BUN) and a significant decrease in estimated creatinine clearance and potassium level, which corresponded with the alterations in the histopathology of the renal tissue. OELE significantly ameliorated the nephrotoxic effects of cisplatin as dose-dependent. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) in females is an endocrine pathological condition of reproductive age which is usually caused by insulin resistance, hyperlipidemia, and oxidative stress. This research was aimed at evaluating the therapeutic effect of the Centratherum anthelminticum seed extract (CA) against PCOS in rodents as it is traditionally used to treat diabetes, inflammation, and gynecological problems. The CA was chemically characterized by high-performance liquid chromatography-diode array detection (HPLC-DAD). For the induction of PCOS, a high-fat diet (HFD) was given to all female Wistar rats for nine weeks except the normal control group, which was given a normal chow diet. Estradiol valerate was given to all rats except normal control. After the induction of PCOS, oral metformin (300 mg/kg) was given to the standard group, while CA was orally administered to diseased rats at 250, 500, and 750 mg/kg/day for 28 days. HPLC-DAD analysis revealed that kaempferol-3-pcoumaroylglucoside was present in the highest amount (146.8 ± 1.8 mg/g) of the extract followed by ferulic acid and malvidin-3-(6-caffeoyl)-glucoside. The in vivo results revealed a marked reduction in cholesterol and triglyceride levels in CA treatment groups. A significant rise was observed in progesterone and follicle stimulating hormone with a decrease in luteinizing hormone in the treatment groups as compared to disease control, which indicated normalization of the estrus cycle. The decrease in insulin resistance was characterized by low serum insulin levels in treatment groups. Treatment with CA also reduced inflammatory markers, such as IL-6 and NF-κB in PCOS rats. NrF2 and oxidative stress markers such as catalase, superoxide dismutase, malondialdehyde, and reduced glutathione were also improved by CA in the ovary of diseased rats. Histopathological examination showed the different developmental stages of normal follicles in CA-treated diseased rats which were indicative of a normal fertile estrous cycle. Overall, the results confirmed the efficacy of CA against PCOS in treating estradiol-HFD-induced PCOS due to its antidiabetic, anti-inflammatory, antihyperlipidemic, and antioxidant properties. [ABSTRACT FROM AUTHOR]

Objective. To investigate the role of aberrant Dyrk1a expression in phosphorylation modification at the α-synuclein serine 129 (Ser129) site to analyze its molecular mechanism in mediating apoptosis of PD. Methods. The protein level of P-α-synuclein (Ser129), α-synuclein, Bcl-2, Bax, active caspase 3, GSK3β, PI3K, AKT, and cyclinD1 were detected. The mRNA transcript levels of Dyrk1a and DAT and protein levels of IL-1β, IL-6, COX-2, and TNF-α were detected. Results. P-α-synuclein (Ser129), α-synuclein, Bax, active caspase 3, GSK3β, and cyclinD1 expressions were decreased in Dyrk1a-AAV-ShRNA (P < 0.05), and Bcl-2, AKT, and PI3K expressions were increased (P < 0.05). Increased TH protein expression was shown in Dyrk1a-AAV-ShRNA (P < 0.05). Dyrk1a mRNA was decreased in the Dyrk1a-AAV-ShRNA group (P < 0.05), and DAT mRNA was increased (P < 0.05). IL-1β, IL-6, COX-2, and TNF-α protein levels were decreased in Dyrk1al-AAV-Sh-RNA (P < 0.05). Transcriptome sequencing showed that Fam220a, which was expected to activate STAT family protein binding activity and participate in the negative regulation of transcription through RNA polymerase II and protein dephosphorylation showed differentially upregulated expression. The untargeted metabolome showed that the major compounds in the Dyrk1a-AAV-ShRNA group were hormones and transmission mediators and the most metabolism-related pathways. Fam220a showed differentially upregulated expression, and differentially expressed genes were enriched for the neuroactive ligand-receptor interaction, vascular smooth muscle contraction, and melanogenesis-related pathways. Conclusion. Abnormal Dyrk1a expression can affect α-synuclein phosphorylation modifications, and dyrk1a knockdown activates the PI3K/AKT pathway and reduces dopaminergic neuron apoptosis. It provides a theoretical basis for the group to further investigate the molecular mechanism. [ABSTRACT FROM AUTHOR]

Current approaches are incurable for rheumatoid arthritis (RA). Regulatory T (Treg) cells and T helper cells (Th1 and Th17) are crucial in controlling the process of RA, which is characterized by inflammatory cell infiltration and bone destruction. Carnosol is an orthodiphenolic diterpene that has been extensively applied in traditional medicine for the treatment of multiple autoimmune and inflammatory diseases. Herein, we indicate that administration of carnosol dramatically alleviated the severity of collagen-induced arthritis (CIA) model with a decreased clinical score and inflammation reduction. Cellular mechanistically, carnosol inhibits the Th17 cell differentiation and maintains Treg cell suppressive function in vitro and in vivo. Meanwhile, it also restrains Treg cells from transdifferentiation into Th17 cells under inflammatory milieu. Furthermore, carnosol modulates the function of Th17 and Treg cells possibly via limiting IL-6R (CD126) expression. Collectively, our results suggest that carnosol can alleviate the severity of CIA via hiding Th17 cell differentiation and maintain the stability of Treg cells. Administration of carnosol can be applied as a potential therapy for patients with RA. [ABSTRACT FROM AUTHOR]

Background. Both high-fat diet (HFD) and 4-nonylphenol (4-NP) could affect fat formation in adipose tissue individually. We investigated whether HFD promote abnormal adipose tissue formation caused by early exposure to 4-NP in life and preliminarily explore the possible mechanisms involved. Methods. The first-generation rats were treated with HFD on postnatal day after pregnant rats exposure to 5 ug/kg/day 4-NP. Then, the second generation rats started to only receive normal diet without 4-NP or HFD. We analyzed organ coefficient and histopathology of fat tissues, biochemical index, and gene level involved in lipid metabolism in female offspring rats. Results. HFD and 4-NP interaction synergistically increased birth weight, body weight, and organ coefficients of adipose tissue in offspring female rats. HFD accelerately aggravated abnormal lipid metabolism and increased the adipocyte mean areas around the uterus of the offspring female rats induced by prenatal exposure to 4-NP. HFD also facilitate the regulation of gene expression involved lipid metabolism in offspring female rats induced by perinatal exposure to 4-NP, even passed on to the second generation of female rats. Moreover, HFD and 4-NP interaction synergistically declined the gene and protein expression of estrogen receptor (ER) in the adipose tissue of second-generation female rats. Conclusion. HFD and 4-NP synergistically regulate the expression of lipid metabolism genes in adipose tissue of F2 female rats and promote adipose tissue generation, leading to obesity in offspring rats, which is closely related to low expression of ER. Therefore, ER genes and proteins may be involved in the synergistic effect of HFD and 4-NP. [ABSTRACT FROM AUTHOR]

Shudage-4, an ancient and well-known formula in traditional Mongolian medicine comprising four different types of traditional Chinese medicine, is widely used in the treatment of gastric ulcers. However, the potential material basis and molecular mechanism of Shudage-4 in attenuating stress-induced gastric ulcers remain unclear. This study aimed to first explore the potential material basis and molecular mechanism of Shudage-4 in attenuating gastric ulcers in rats. The chemical constituents and transitional components in the blood of Shudage-4 were identified by ultra-performance liquid chromatography time-of-flight mass spectrometry (UPLC-TOF-MS). The rat gastric ulcer model was induced by water immersion restraint stress (WIRS). The ulcer damage to gastric tissue was measured at the gross anatomical level and pathological level by hematoxylin-eosin (HE) staining of gastric tissue. RNA sequencing of gastric tissue and plasma metabolomics were performed to analyze the mechanism of Shudage-4 against gastric ulcers. A Pearson correlation analysis was performed to explore the association between serum metabolites and gene expression of gastric tissue. A total of 30 chemical constituents were identified in Shudage-4 by UPLC-TOF-MS. Among 30 constituents, 13 transitional components in the blood were considered as the potential material basis. Shudage-4 treatment had a significant effect on WIRS-induced gastric ulcers in rats. HE staining of gastric tissue illustrated that WIRS-induced ulcer damage was suppressed by Shudage-4 treatment. RNA sequencing of gastric tissue showed that 282 reversed expression genes in gastric tissue were related to Shudage-4 treatment, and gene set enrichment analysis revealed that Shudage-4 treatment significantly inhibited gene set expression related to reactive oxygen species (ROS), which was also validated by detecting rat gastric tissue MDA, GSH, SOD, GSH-Px, and CAT activities. The plasma metabolomic data demonstrated that 23 significantly differential metabolites were closely associated with the Shudage-4 treatment. The further multiomics joint analysis found that significantly upregulated 5 plasma metabolites in Shudage-4-treated rats compared to model rats were negatively correlated with gene set expression related to ROS in gastric tissue. Shudage-4 alleviated WIRS-induced gastric ulcers by inhibiting ROS generation, which was achieved by regulating plasma metabolites level. [ABSTRACT FROM AUTHOR]

We propose an enhanced method to accurately retrieve time-activity curves (TACs) of blood and tissue from dynamic 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) cardiac images of mice. The method is noninvasive and consists of using a constrained nonnegative matrix factorization algorithm (CNMF) applied to the matrix (A) containing the intensity values of the voxels of the left ventricle (LV) PET image. CNMF factorizes A into nonnegative matrices H and W , respectively, representing the physiological factors (blood and tissue) and their associated weights, by minimizing an extended cost function. We verified our method on 32 C57BL/6 mice, 14 of them with acute myocardial infarction (AMI). With CNMF, we could break down the mouse LV into myocardial and blood pool images. Their corresponding TACs were used in kinetic modeling to readily determine the [18F]FDG influx constant ( K i ) required to compute the myocardial metabolic rate of glucose. The calculated K i values using CNMF for the heart of control mice were in good agreement with those published in the literature. Significant differences in K i values for the heart of control and AMI mice were found using CNMF. The values of the elements of W agreed well with the LV structural changes induced by ligation of the left coronary artery. CNMF was compared with the recently published method based on robust unmixing of dynamic sequences using regions of interest (RUDUR). A clear improvement of signal separation was observed with CNMF compared to the RUDUR method. [ABSTRACT FROM AUTHOR]

The acute toxicity and hypokinetic activity induced by menthofuran on the gastrointestinal tract of rodents were investigated in the present study. An absence of acute toxicity was observed. Menthofuran delayed gastric emptying at oral doses of 25, 50, and 100 mg/kg in the experimental model of phenol red, as well as it reduced the intestinal transit at oral doses of 50 and 100 mg/kg. Interestingly, a scopolamine-similar hypokinetic effect was observed for menthofuran. In the experimental model of castor oil-induced intestinal hypermotility, menthofuran (50 and 100 mg/kg) reduced the number of loose stools as observed for the normal group. Additionally, menthofuran induced a marked concentration-dependent relaxation in rat ileum segments precontracted with KCl (EC50 = 0.059 ± 0.008 μg/mL) or carbachol (EC50 = 0.068 ± 0.007 μg/mL). These results suggest the possible decrease of calcium influx underlying the effects of menthofuran on the gastrointestinal tract, which opens the door for further study regarding this potential application for the treatment of gastrointestinal disorders, noting possible limitations of its use due to adverse effects in children. [ABSTRACT FROM AUTHOR]