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Ganoderma tsugae, a medicinal mushroom and one of Taiwan's significant commercially cultivated species, contains polysaccharides and triterpenoids reported to possess anticancer effects. This study investigated the G. tsugae water extract (GTWE) for its inhibitory mechanism against lung metastatic melanoma (LMM) and B16F10 cells. The antioxidant capacity and flow cytometry showed that GTWE reduced the production of cellular reactive oxygen species dose-dependently. MTT and wound healing assays further demonstrated that GTWE suppressed melanoma cell migration and viability. qRT-PCR and western blotting verified mechanisms of apoptosis, GTWE decreased the BCL2 expressions and upregulated Bax and cleaved caspase-9 protein. These findings suggest GTWE is a potential therapeutic agent in vitro and in vivo for treating melanoma cancer.

Abstract Extracellular communication, in other words, crosstalk between cells, has a pivotal role in the survival of an organism. This communication occurs by different methods, one of which is extracellular vesicles. Exosomes, which are small lipid extracellular vesicles, have recently been discovered to have a role in signal transduction between cells inside the body. These vesicles contain important bioactive molecules including lipids, proteins, DNA, mRNA, and noncoding RNAs such as microRNAs (miRNAs). Exosomes are secreted by all cells including immune cells (macrophages, lymphocytes, granulocytes, dendritic cells, mast cells) and tumor cells. The tumor microenvironment (TME) represents a complex network that supports the growth of tumor cells. This microenvironment encompasses tumor cells themselves, the extracellular matrix, fibroblasts, endothelial cells, blood vessels, immune cells, and non-cellular components such as exosomes and cytokines. This review aims to provide insights into the latest discoveries concerning how the immune system communicates internally and with other cell types, with a specific focus on research involving exosomal miRNAs in macrophages, dendritic cells, B lymphocytes, and T lymphocytes. Additionally, we will explore the role of exosomal miRNA in the TME and the immunomodulatory effect.

Esophageal cancer (EC) is one of the most aggressive gastrointestinal cancers. Despite improvements in therapies, the survival rate of patients with EC remains low. Metastasis accounts for up to 90% of cancer-related deaths, and resistance to anti-neoplastic therapeutics is also a main cause of poor survival. Thus, metastasis and drug resistance are undoubtedly the two main challenges in cancer treatment. Among the different categories of noncoding RNAs, lncRNAs have historically drawn less attention. However, lncRNAs have gradually become a research hotspot, and increasing research has demonstrated that lncRNAs participate in the tumorigenesis of multiple types of cancer, including EC. Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides in length that play important roles in epigenetics, transcription regulation, and posttranscriptional processing. In this review, we elucidated the role of lncRNAs in the metastasis and drug resistance of EC and discussed their potential clinical applications and related limitations. With a better understanding of the underlying mechanisms of lncRNAs, we can identify therapeutic targets for EC in the future.

ABSTRACT: Diabetes has become a global concern at present, among which type 2 diabetes mellitus (T2DM) accounts for approximately 90 %–95 % of patients. T2DM is a type of metabolic disorder syndrome that results from a genetic defect, and it is based on insulin resistance and an insulin secretion disorder. The occurrence of T2DM is usually the outcome of both genetic and environmental factors and their interactions. The etiology and pathogenesis of diabetes have not been fully elucidated, and no radical therapeutic cure has been found. Patients with T2DM suffer from complications such as the development of a chronic hyperglycemic condition and even serious metabolic disorders and organ damage in the body and depression and dementia, in addition to other chronic complications. Many studies have suggested that diet is crucial in the development of diabetes and the control of blood glucose. Natural substances have the characteristics of low toxicity and few side effects and may be key to the development of diabetic health products and preventive treatments. This paper reviews the etiology, pathogenesis, risks, treatments and diets related to T2DM to summarize the types of recently available natural products, from both local and foreign sources, for lowering blood glucose at home and their application in supplementary hypoglycemic foods. The key findings and conclusions suggest that there are various known T2DM-inducing factors, including genetic and environmental factors and three types of hybrid factors.

The COVID-19 pandemic brought the world to a standstill, posing unprecedented challenges for healthcare systems worldwide. The overwhelming number of patients infected with the virus placed an enormous burden on healthcare providers, who struggled to cope with the sheer volume of cases. Furthermore, the lack of effective treatments or vaccines means that quarantining has become a necessary measure to slow the spread of the virus. However, quarantining places a significant burden on healthcare providers, who often lack the resources to monitor patients with mild symptoms or asymptomatic patients. In this study, we propose an Internet of Things (IoT)-based wearable health monitoring system that can remotely monitor the exact locations and physiological parameters of quarantined individuals in real time. The system utilizes a combination of highly miniaturized optoelectronic and electronic technologies, an anti-epidemic watch, a mini-computer, and a monitor terminal to provide real-time updates on physiological parameters. Body temperature, peripheral oxygen saturation (SpO2), and heart rate are recorded as the most important measurements for critical care. If these three physiological parameters are aberrant, then it could represent a life-endangering situation and/or a short period over which irreversible damage may occur. Therefore, these parameters are automatically uploaded to a cloud database for remote monitoring by healthcare providers. The monitor terminal can display real-time health data for multiple patients and provide early warning functions for medical staff. The system significantly reduces the burden on healthcare providers, as it eliminates the need for manual monitoring of patients in quarantine. Moreover, it can help healthcare providers manage the COVID-19 pandemic more effectively by identifying patients who require medical attention in real time. We have validated the system and demonstrated that it is well suited to practical application, making it a promising solution for managing future pandemics. In summary, our IoT-based wearable health monitoring system has the potential to revolutionize healthcare by providing a cost-effective, remote monitoring solution for patients in quarantine. By allowing healthcare providers to monitor patients remotely in real time, the burden on medical resources is reduced, and more efficient use of limited resources is achieved. Furthermore, the system can be easily scaled to manage future pandemics, making it an ideal solution for managing the health challenges of the future.

Abstract Urological chronic pelvic pain syndrome (UCPPS) manifests as pelvic pain with frequent urination and has a 10% prevalence rate without effective therapy. Nanoceria (cerium oxide nanoparticles [CNPs]) were synthesized in this study to achieve potential long‐term pain relief, using a commonly used UCPPS mouse model with cyclophosphamide‐induced cystitis. Transcriptome sequencing analysis revealed that serpin family B member 2 (SerpinB2) was the most upregulated marker in mouse bladder, and SerpinB2 was downregulated with CNP pretreatment. The transcriptome sequencing analysis results agreed with quantitative polymerase chain reaction and western blot analysis results for the expression of related mRNAs and proteins. Analysis of Gene Expression Omnibus (GEO) datasets revealed that SerpinB2 was a differentially upregulated gene in human UCPPS. In vitro SerpinB2 knockdown downregulated proinflammatory chemokine expression (chemokine receptor CXCR3 and C‐X‐C motif chemokine ligand 10) upon treatment with 4‐hydroperoxycyclophosphamide. In conclusion, CNP pretreatment may prevent the development of UCPPS, and reactive oxygen species (ROS) scavenging and SerpinB2 downregulation may modulate the immune response in UCPPS.

In this study, we aimed to isolate and identify the bioactive compounds from 5-year pickled radish. The pickled radish was extracted with methanol or ethyl acetate. Sephadex LH-20, normal phase and reverse phase silica gel column chromatography were used for separation and purification, combined with thin layer chromatography (TLC), high performance liquid chromatography (HPLC), electrospray mass spectrometry (ESI-MS), nuclear magnetic resonance spectroscopy (NMR) technology for structural identification. The results showed that 6 compounds were separated and purified from methanol and ethyl acetate extracts of 5-year-old pickled radish. The structures were identified as 5-hydroxymethylfurfural, β-sitosterol, β-sitosterol-3-O-glucose glycosides, α-linolenic acid, 1-monopalmitin and chaenomic acid A. Using molecular docking, it was determined that β-sitosterol and its derivative β-sitosterol-3-O-glucose glycosides have high affinity for five antioxidant enzymes, and there were multiple hydrogen bonds between them. These results indicated that pickled radishes might be used as an important source of natural chemical substances.

In this study, cereals with high starch content, including brown rice, corn, and buckwheat were pretreated by extrusion. The physicochemical properties of extruded-puffed cereals obtained from different extrusion conditions were analyzed herein. The puffed extrudates exhibited lower bulk density, higher water solubility and gelatinization as compared to untreated cereals. The FTIR-ATR results confirmed a decrease in the crystalline structure of extruded-puffed cereals. A higher Vmax/Km value was observed in the enzymatic saccharification of puffed extrudates that significantly improved hydrolysis rate and yield. Finally, the high-maltose syrup was produced via the enzymatic hydrolysis of extruded-puffed cereals at high substrate concentrations (20 %). After hydrolysis for 180 min at an enzyme substrate ratio (E/S ratio) of 0.2, the syrup with dextrose equivalent (DE) value of 63, 62, and 61 were obtained from extruded-puffed brown rice, corn, and buckwheat, respectively. Our results showed the potential of using extruded-puffed cereals for producing high-maltose syrup.

The rising climate change concerns over the excessive exploitation of non-renewable sources have necessitated the need for alternative renewable and eco-friendly resources for the production of innovative materials, achieving the targets of bioeconomy. Lignocellulosic biomass (LB) constituted by polymeric sugars and lignin is an abundantly available plant-based renewable material in the form of agro-industrial food waste and crop residues that can be exploited for the production of an array of value-added chemicals and bioproducts. Cellulose is the most abundant natural and biodegradable organic polymer on earth derived from LB, with wide scale applications in the lignocellulosic biorefineries and food industries. The negative effects of food waste from agro-industrial activities could be reduced through the recovery of cellulose from these wastes and converting it into valuable forms. However, the extraction of cellulose from LB is a difficult task owing to the recalcitrant nature of biomass that restricts the easy accessibility of cellulose for value addition. Therefore, a suitable cellulose extraction method through the fractionation of LB is necessary for a better cellulose yield. Furthermore, owing to the enormous potential of nanocellulose (NC), researchers are keenly interested in developing ecologically acceptable cellulose extraction methods. Cellulose nanofibrils and nanocrystals confer excellent mechanical properties, non-toxic characteristics and biodegradability, due to which they possess wide-scale applications in diverse industrial sectors. The current review emphasizes the potential role of cellulose extraction and NC production from agro-food waste. The different pretreatment methods for their extraction from LB are outlined. The applications of nanocellulose in different areas are also discussed. The review also highlights the recent trends, challenges and future directions in the development of cellulose and NC-based commercial products.

Abstract Background Gene silencing using siRNA can be a new potent strategy to treat many incurable diseases at the genetic level, including cancer and viral infections. Treatments using siRNA essentially requires an efficient and safe method of delivering siRNA into cells while maintaining its stability. Thus, we designed novel synergistic fusion peptides, i.e., SPACE and oligoarginine. Results Among the novel fusion peptides and siRNAs, nanocomplexes have enhanced cellular uptake and gene silencing effect in vitro and improved retention and gene silencing effects of siRNAs in vivo. Oligoarginine could attract siRNAs electrostatically to form stable and self-assembled nanocomplexes, and the SPACE peptide could interact with the cellular membrane via hydrogen bonding. Therefore, nanocomplexes using fusion peptides showed improved and evident cellular uptake and gene silencing of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) via the lipid raft-mediated endocytosis pathway, especially to the HDFn cells of the skin, and all of the fusion peptides were biocompatible. Also, intratumorally injected nanocomplexes had increased retention time of siRNAs at the site of the tumor. Finally, nanocomplexes demonstrated significant in vivo gene silencing effect without overt tissue damage and immune cell infiltration. Conclusions The new nanocomplex strategy could become a safe and efficient platform for the delivery of siRNAs into cells and tissues to treat various target diseases through gene silencing.

This study aimed to use the k-nearest neighbor (kNN) algorithm, which combines gait stability and symmetry derived from a normalized cross-correlation (NCC) analysis of acceleration signals from the bilateral ankles of older adults, to assess fall risk. Fifteen non-fallers and 12 recurrent fallers without clinically significant musculoskeletal and neurological diseases participated in the study. Sex, body mass index, previous falls, and the results of the 10 m walking test (10 MWT) were recorded. The acceleration of the five gait cycles from the midsection of each 10 MWT was used to calculate the unilateral NCC coefficients for gait stability and bilateral NCC coefficients for gait symmetry, and then kNN was applied for classifying non-fallers and recurrent fallers. The duration of the 10 MWT was longer among recurrent fallers than it was among non-fallers (p < 0.05). Since the gait signals were acquired from tri-axial accelerometry, the kNN F1 scores with the x-axis components were 92% for non-fallers and 89% for recurrent fallers, and the root sum of squares (RSS) of the signals was 95% for non-fallers and 94% for recurrent fallers. The kNN classification on gait stability and symmetry revealed good accuracy in terms of distinguishing non-fallers and recurrent fallers. Specifically, it was concluded that the RSS-based NCC coefficients can serve as effective gait features to assess the risk of falls.

Wearable devices are being developed faster and applied more widely. Wearables have been used to monitor movement-related physiological indices, including heartbeat, movement, and other exercise metrics, for health purposes. People are also paying more attention to mental health issues, such as stress management. Wearable devices can be used to monitor emotional status and provide preliminary diagnoses and guided training functions. The nervous system responds to stress, which directly affects eye movements and sweat secretion. Therefore, the changes in brain potential, eye potential, and cortisol content in sweat could be used to interpret emotional changes, fatigue levels, and physiological and psychological stress. To better assess users, stress-sensing devices can be integrated with applications to improve cognitive function, attention, sports performance, learning ability, and stress release. These application-related wearables can be used in medical diagnosis and treatment, such as for attention-deficit hyperactivity disorder (ADHD), traumatic stress syndrome, and insomnia, thus facilitating precision medicine. However, many factors contribute to data errors and incorrect assessments, including the various wearable devices, sensor types, data reception methods, data processing accuracy and algorithms, application reliability and validity, and actual user actions. Therefore, in the future, medical platforms for wearable devices and applications should be developed, and product implementations should be evaluated clinically to confirm product accuracy and perform reliable research.

Previous reviews have already explored the safety and bioavailability of astaxanthin, as well as its beneficial effects on human body. The great commercial potential in a variety of industries, such as the pharmaceutical and health supplement industries, has led to a skyrocketing demand for natural astaxanthin. In this study, we have successfully optimized the astaxanthin yield up to 12.8 mg/g DCW in a probiotic yeast and purity to 97%. We also verified that it is the desired free-form 3S, 3’S configurational stereoisomer by NMR and FITR that can significantly increase the bioavailability of astaxanthin. In addition, we have proven that our extracted astaxanthin crystals have higher antioxidant capabilities compared with natural esterified astaxanthin from H. pluvialis. We also screened for potential adverse effects of the pure astaxanthin crystals extracted from the engineered probiotic yeast by dosing SD rats with 6, 12, and 24 mg/kg/day of astaxanthin crystals via oral gavages for a 13-week period and have found no significant biological differences between the control and treatment groups in rats of both genders, further confirming the safety of astaxanthin crystals. This study demonstrates that developing metabolically engineered microorganisms provides a safe and feasible approach for the bio-based production of many beneficial compounds, including astaxanthin.

In this study, the water extract of Cordyceps militaris (Linn.) Link (CM) was used as a functional material to investigate the inhibitory mechanisms on B16F10 and lung metastatic melanoma (LMM) cells. Reducing power, chelating ability, and 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays were applied for antioxidative capacities, and we obtained positive results from the proper concentrations of CM. To examine the ability of CM in melanoma proliferation inhibition and to substantiate the previous outcomes, three cellular experiments were performed via (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT, a tetrazole) assay, cell migration, and invasion evaluation. The addition of CM to the incubation medium increased the number of CD8+ T cells significantly, which improved the immunogenicity. This study showed that CM exhibits various biological capabilities, including antioxidation, anti-tumor, tumor invasion suppression, and T cytotoxic cell activity promotion.

[This corrects the article DOI: 10.1371/journal.pone.0197744.].

Abstract Neuroinflammation is primarily characterized by overexpression of proinflammatory mediators produced by glial activation or immune cell infiltration. Several kinases have been shown to be critical mediators in neuroinflammation. One of the largest groups of kinases is protein kinases, which have been the second most studied group of drug targets after G-protein-coupled receptors. Thus far, most of the approved kinase inhibitor drugs are adenosine triphosphate-competitive inhibitors with various off-target liabilities because of cross-reactivities; however, marine-derived compounds provide opportunities for discovering allosteric kinase inhibitors. This review summarizes the potential of marine-derived protein kinase inhibitors in the field of neuroinflammatory diseases, such as Parkinson disease, Alzheimer disease, multiple sclerosis, and pain. The previous studies from 1990 to 2017 in this review have shown that marine-derived protein kinase inhibitors have great potential to elicit anti-neuroinflammatory or neuroprotective responses in in vitro and in vivo models of neuroinflammatory diseases. This suggests that further exploration and investigation of these marine-derived protein kinase inhibitors on neuroinflammatory diseases are warranted. Therefore, this review may inspire further discovery of new protein kinase inhibitors from a marine origin and additional neuroscience studies focusing on these valuable marine-derived protein kinase inhibitors.

The optimization of fermentation medium is important for synthetic biological secondary metabolite productions. The effect of rotation speed, inoculum amount, and medium supplements on the cell growth and Lycogen⢠secretion of photobacterium Rhodobacter sphaeroides WL-APD911 was evaluated. The results reveal that a higher rotational speed exhibit a higher cell density, and the increasing in the amount of inoculum amount show a slight augment on the growth of R. sphaeroides WL-APD911.In the case of nitrogen sources adding, Lycogen⢠production was achieved with a 0.5 mM l-lysine supplementation. Moreover, the attention of Tween 80 presented a tremendous increase in the secondary metabolite. Response surface methodology (RSM) exhibited the optimization of medium supplements for Lycogen⢠invention is accomplished at molasses concentration of 10 g/L, yeast extract concentration of 40 g/L, 0.3% Tween 80 and NaCl concentration of 5 g/L, respectively. Further, the batch fermentation is carried out in both 5 L and 20 L fermentors to study the scale-up process factors to be adopted. At a 20 L fermentor, Lycogen⢠yields under the optimal culture condition are over 2 times than in the shake flask. The present results provide the Lycogen⢠optimal culture mediums, scale-up procedures and efficient extractions from R. sphaeroides WL-APD911. Keywords: Rhodobacter sphaeroides WL-APD911, Lycogenâ¢, Response surface methodology (RSM), Ferementation

Different types of cells, such as endothelial cells, tumor-associated fibroblasts, pericytes, and immune cells, release extracellular vesicles (EVs) in the tumor microenvironment. The components of EVs include proteins, DNA, RNA, and microRNA. One of the most important functions of EVs is the transfer of aforementioned bioactive molecules, which in cancer cells may affect tumor growth, progression, angiogenesis, and metastatic spread. Furthermore, EVs affect the presentation of antigens to immune cells via the transfer of nucleic acids, peptides, and proteins to recipient cells. Recent studies have also explored the potential application of EVs in cancer treatment. This review summarizes the mechanisms by which EVs regulate melanoma development, progression, and their potentials to be applied in therapy. We initially describe vesicle components; discuss their effects on proliferation, anti-melanoma immunity, and drug resistance; and finally focus on the effects of EV-derived microRNAs on melanoma pathobiology. This work aims to facilitate our understanding of the influence of EVs on melanoma biology and initiate ideas for the development of novel therapeutic strategies.

This study assessed the use of astaxanthin as an anticancer agent for increasing inhibition to melanoma cells (A375 and A2058). Wound healing and invasion assays presented that astaxanthin treatment reduced melanoma cell migration in a dose-dependent manner. The effects on melanoma cell migration were conferred via suppressed expressions of matrix metalloproteinases 1, 2 and 9. Dichlorofluorescein diacetate assay further showed that astaxanthin treatment reduced production of cellular reactive oxygen species. Cellular proliferation assay revealed potent dose-dependent inhibiting effects on melanoma cells. One-dimensional flow cytometric analysis demonstrated that astaxanthin induced cell cycle arrest in G1 phase. Mechanisms of apoptosis were verified by double fluorescence staining with annexin V-fluorescein isothiocyanate and propidium iodide. The antitumor effects of astaxanthin significantly decreased tumor size in a xenograft model. In summary, the experimental results showed that astaxanthin has potent in vivo and in vitro inhibiting effects on melanoma tumor growth for developing as chemotherapeutic agents.

Natural products are favored because of their non-toxicity, low irritants, and market reacceptance. We collected examples, according to ancient wisdom, of natural products to be applied in transdermal delivery. A transdermal delivery system, including different types of agents, such as ointments, patches, and gels, has long been used for skin concerns. In recent years, many novel transdermal applications, such as nanoemulsions, liposomes, lipid nanoparticles, and microneedles, have been reported. Nanosized drug delivery systems are widely applied in natural product deliveries. Nanosized materials notably enhance bioavailability and solubility, and are reported to improve the transdermal permeation of many substances compared with conventional topical formulations. Natural products have been made into nanosized biomaterials in order to enhance the penetration effect. Before introducing the novel transdermal applications of natural products, we present traditional methods within this article. The descriptions of novel transdermal applications are classified into three parts: liposomes, emulsions, and lipid nanoparticles. Each section describes cases that are related to promising natural product transdermal use. Finally, we summarize the outcomes of various studies on novel transdermal agents applied to skin treatments.

Astragalin, isolated from flowers of Rosa chinensis Jacq., is a kind of flavonoid, with anti-inflammatory, antioxidant, antiviral, analgesic, antibacterial, antiallergic, and antihepatotoxic effects. However, no studieson the procoagulant effect of astragalin have been reported. This study aimed to investigate the procoagulant activity of astragalin and its mechanism. Its procoagulant effect was investigated by activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time (PT), and fibrinogen (FIB) in vitro, and a rat model established by heparin sodium was used to evaluate the mechanism for the procoagulant effect in vivo. The results showed that astragalin had good procoagulant effects compared with the control group in vitro. Compared with the model group in vivo, astragalin could shorten the coagulation time and significantly increase the number of platelets. Meanwhile, astragalin could significantly reduce the effectual time of PT and APTT and increase the content of FIB. The contents of 6-keto-PGF1α and eNOS significantly decreased. Astragalin could increase whole blood viscosity (WBV), plasma viscosity (PV), erythrocyte sedimentation rate (ESR) and packedcell volume (PCV). All of the above revealed that astragalin had good procoagulant effects by promoting the intrinsic and extrinsic coagulation system.

Tea (Camellia sinensis) contains high level of antioxidant elements and is a well-known beverage consumed worldwide. The purpose of this study is to compare different concentrations of green tea, black tea, oolong tea 861, oolong tea 732, and jasmine green tea. These five types of tea extracts were known to have antioxidative properties, reducing power, and metal ion chelating activity. The current study compared these five extracts in terms of their inhibiting effects on human malignant melanoma: A2058 and A375. To determine the cell viability between normal cell and malignant melanoma cells, an MTT assay was applied to evaluate the cytotoxic potential on human melanoma cells, with all tea extracts showing decreased cell viability with increasing tea extract concentrations. Cytotoxicity on HaCat (normal skin cells) showed no effect on the cell viabilities at lower concentrations of the tea extracts. These results suggest the antioxidative effect of five tea extracts that protect against oxidation and melanoma production, with green tea and jasmine green tea showing the lowest cell viability when tested against malignant melanoma cells.

Adipose-derived stem cells (ADSCs) transplant has been reported to be a potential treatment for burn wounds. However, the effects of autogenicity and allogenicity of ADSCs on burn wound healing have not been investigated and the method for using ADSCs still needs to be established. This study compared the healing effects of autologous and allogenic ADSCs and determined an optimal method of using ADSCs to treat acute burn wounds. Experiments were performed in 20 male Wistar rats (weight, 176-250 g; age, 6-7 weeks). Two identical full-thickness burn wounds (radius, 4 mm) were created in each rat. ADSCs harvested from inguinal area and characterized by their high multipotency were injected into burn wounds in the original donor rats (autologous ADSCs group) or in other rats (allogenic ADSCs group). The injection site was either the wound center or the four corners 0.5 cm from the wound edge. The reduction of burn surface areas in the two experimental groups and in control group were evaluated with Image J software for 15 days post-wounding to determine the wound healing rates. Wound healing was significantly faster in the autologous ADSCs group compared to both the allogenic ADSCs group (p

The potential physics differences of Chinese traditional stewed pork during mastication were investigated. Ten subjects chewed and expectorated the fat and lean layers of stewed pork with brown sauce at different stages of mastication. The produced boluses were analyzed for their physical properties. The results suggested the subjects’ saliva secretion and moisture content of the boluses during mastication increased significantly depending on subjects and food types studied (P

To date, no study has been conducted to explore the bioactivity of the crinoid Comanthus bennetti. Here we report the anti-inflammatory properties of comaparvin (5,8-dihydroxy-10-methoxy-2-propylbenzo[h]chromen-4-one) based on in vivo experiments. Our preliminary screening for anti-inflammatory activity revealed that the crude extract of Comanthus bennetti significantly inhibited the expression of pro-inflammatory proteins in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophage cells. Comaparvin isolated from crinoids significantly decreased the expression of inducible nitric oxide synthase (iNOS) protein and mRNA in LPS-stimulated macrophage cells. Moreover, our results showed that post-treatment with comaparvin significantly inhibited mechanical allodynia, thermal hyperalgesia and weight-bearing deficits in rats with carrageenan-induced inflammation. Comaparvin also attenuated leukocyte infiltration and iNOS protein expression in carrageenan-induced inflamed paws. These results suggest that comaparvin is a potential anti-inflammatory therapeutic agent against inflammatory pain.

Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI) model of neuropathic pain. First, we found that a single intrathecal (i.t.) administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-μg flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-β1 (TGF-β1) at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-β type I receptor, blocked the analgesic effects of flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-β1 may be involved in the anti-neuroinflammatory and analgesic effects of flexibilide.

In this research we utilized extracts from two different nature products, Achatina fulica and Heimiella retispora, to enhance skin moisturizing abilities, anti-oxidative properties, and cell proliferations. It was observed that two polysaccharides with anti-oxidative effects by chelating metal ions reduced oxidative stress and further blocked the formation of reactive oxygen species syntheses. To detect whether there was a similar effect within the cellular mechanism, a flow cytometry was applied for sensing the oxidative level and it was found that both materials inhibited the endogenous oxidative stress, which was induced by phorbol-12-myristate-13-acetate (PMA). Both polysaccharides also stimulated the production of collagen to maintain skin tightness and a moisturizing effect. In summary, we developed two macromolecular polysaccharides with potential applications in dermal care.

Burn-induced neuropathic pain is complex, and fat grafting has reportedly improved neuropathic pain. However, the mechanism of fat grafting in improving neuropathic pain is unclear. Previous investigations have found that neuroinflammation causes neuropathic pain, and anti-inflammatory targeting may provide potential therapeutic opportunities in neuropathic pain. We hypothesized that fat grafting in burn scars improves the neuropathic pain through anti-inflammation. Burn-induced scar pain was confirmed using a mechanical response test 4 weeks after burn injuries, and autologous fat grafting in the scar area was performed simultaneously. After 4 weeks, the animals were sacrificed, and specimens were collected for the inflammation test, including COX-2, iNOS, and nNOS in the injured skin and spinal cord dorsal horns through immunohistochemistry and Western assays. Furthermore, pro-inflammatory cytokines (IL-1 β and TNF-α) in the spinal cord were collected. Double immunofluorescent staining images for measuring p-IκB, p-NFκB, p-JNK, and TUNEL as well as Western blots of AKT, Bax/Bcl-2 for the inflammatory process, and apoptosis were analyzed. Fat grafting significantly reduced COX2, nNOS, and iNOS in the skin and spinal cord dorsal horns, as well as IL-1β and TNF-α, compared with the burn group. Moreover, regarding the anti-inflammatory effect, the apoptosis cells in the spinal cord significantly decreased after the fat grafting in the burn injury group. Fat grafting was effective in treating burn-induced neuropathic pain through the alleviation of neuroinflammation and ameliorated spinal neuronal apoptosis.

Cinnamomum osmophloeum Kanehira belongs to the Lauraceae family of Taiwan’s endemic plants. In this study, C. osmophloeum Kanehira extract has shown inhibition of tyrosinase activity on B16-F10 cellular system first. Whether extracts inhibited mushroom tyrosinase activity was tested, and a considerable inhibition of mushroom tyrosinase activity by in vitro assays was presented. Animal experiments of C. osmophloeum Kanehira were carried out by observing animal wound repair, and the extracts had greater wound healing power than the vehicle control group (petroleum jelly with 8% DMSO, w/v). In addition, the antioxidant capacity of C. osmophloeum Kanehira extracts in vitro was evaluated. We measured C. osmophloeum Kanehira extract’s free radical scavenging capability, metal chelating, and reduction power, such as biochemical activity analysis. The results showed that a high concentration of C. osmophloeum Kanehira extract had a significant scavenging capability of free radical, a minor effect of chelating ability, and moderate reducing power. Further exploration of the possible physiological mechanisms and the ingredient components of skincare product for skin-whitening, wound repair, or antioxidative agents are to be done.

Diabetes is a serious global health problem. Large-scale genome-wide association studies identified loci for type 2 diabetes mellitus (T2DM), including adiponectin (ADIPOQ) gene and transcription factor 7-like 2 (TCF7L2), but few studies clarified the effect of genetic polymorphisms of ADIPOQ and TCF7L2 on risk of T2DM. We attempted to elucidate association between T2DM and polymorphic variations of both in Taiwan’s Chinese Han population, with our retrospective case-control study genotyping single nucleotide polymorphisms (SNPs) in ADIPOQ and TCF7L2 genes both in 149 T2DM patients and in 139 healthy controls from Taiwan. Statistical analysis gauged association of these polymorphisms with risk of T2DM to show ADIPOQ rs1501299 polymorphism variations strongly correlated with T2DM risk (P=0.042), with rs2241766 polymorphism being not associated with T2DM (P=0.967). However, both polymorphisms rs7903146 and rs12255372 of TCF7L2 were rarely detected in Taiwanese people. This study avers that ADIPOQ rs1501299 polymorphism contributes to risk of T2DM in the Taiwanese population.

Betel quid (BQ) is a psychostimulant, an addictive substance, and a group 1 carcinogen that exhibits the potential to induce adverse health effects. Approximately, 600 million users chew a variety of BQ. Areca nut (AN) is a necessary ingredient in BQ products. Arecoline is the primary alkaloid in the AN and can be metabolized through the cytochrome P450 (CYP) superfamily by inducing reactive oxygen species (ROS) production. Full-length CYP26B1 is related to the development of oral pharyngeal cancers. We investigated whether a splice variant of CYP26B1 is associated with the occurrence of ROS related oral and pharyngeal cancer. Cytotoxicity assays were used to measure the effects of arecoline on cell viability in a dose-dependent manner. In vitro and in vivo studies were conducted to evaluate the expression of the CYP26B1 splice variant. The CYP26B1 splice variant exhibited lower expression than did full-length CYP26B1 in the human gingival fibroblast-1 and Ca9-22 cell models. Increased expression of the CYP26B1 splice variant was observed in human oral cancer tissue compared with adjacent normal tissue, and increased expression was observed in patients at a late tumor stage. Our results suggested that the CYP26B1 splice variant is associated with the occurrence of BQ-related oral cancer.

A suitable small animal model may help in the screening and evaluation of new drugs, especially those from natural products, which can be administered at lower dosages, fulfilling an urgent worldwide need. In this study, we explore whether zebrafish could be a model organism for carrageenan-induced abdominal edema. The research results showed that intraperitoneal (i.p.) administration of 1.5% λ-carrageenan in a volume of 20 µL significantly increased abdominal edema in adult zebrafish. Levels of the proinflammatory proteins tumor necrosis factor-α (TNF-α) and inducible nitric oxide synthase (iNOS) were increased in carrageenan-injected adult zebrafish during the development of abdominal edema. An associated enhancement was also observed in the leukocyte marker, myeloperoxidase (MPO). To support these results, we further observed that i.p. methylprednisolone (MP; 1 µg), a positive control, significantly inhibited carrageenan-induced inflammation 24 h after carrageenan administration. Furthermore, i.p. pretreatment with either an anti-TNF-α antibody (1∶5 dilution in a volume of 20 µL) or the iNOS-selective inhibitor aminoguanidine (AG; 1 µg) inhibited carrageenan-induced abdominal edema in adult zebrafish. This new animal model is uncomplicated, easy to develop, and involves a straightforward inducement of inflammatory edema for the evaluation of small volumes of drugs or test compounds.

Sirtuins, NAD+-dependent deacetylases, could target both histones and nonhistone proteins in mammalian cells. Sirt1 is the major sirtuin and has been shown to involve various cellular processes, including antiapoptosis, cellular senescence. Sirt1 was reported to be overexpressed in many cancers, including lung cancer. Sirtinol, a specific inhibitor of Sirt1, has been shown to induce apoptosis of cancer cells by elevating endogenous level of reactive oxygen species. In the study, we investigated the effect of sirtinol on the proliferation and apoptosis of nonsmall cell lung cancer (NSCLC) H1299 cells. The results of proliferation assay and colony formation assay showed the antigrowth effect of sirtinol. The annexin-V staining further confirmed the apoptosis induction by sirtinol treatment. Interestingly, the levels of phosphorylated Akt and β-catenin were significantly downregulated with treating the apoptotic inducing doses. On the contrary, sirtinol treatment causes the significantly increased level of FoxO3a, a proapoptotic transcription factor targeted by Sirt1. These above results suggested that sirtinol may inhibit cell proliferation of H1299 cells by regulating the axis of Akt-β-catenin-FoxO3a. Overall, this study demonstrates that sirtinol attenuates the proliferation and induces apoptosis of NSCLC cells, indicating the potential treatment against NSCLC cells by inhibiting Sirt1 in future applications.

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by tremor, rigidity, bradykinesia, and gait impairment. In a previous study, we found that the marine-derived compound 11-dehydrosinulariolide (11-de) upregulates the Akt/PI3K pathway to protect cells against 6-hydroxydopamine (6-OHDA)-mediated damage. In the present study, SH-SY5Y, zebrafish and rats were used to examine the therapeutic effect of 11-de. The results revealed the mechanism by which 11-de exerts its therapeutic effect: the compound increases cytosolic or mitochondrial DJ-1 expression, and then activates the downstream Akt/PI3K, p-CREB, and Nrf2/HO-1 pathways. Additionally, we found that 11-de could reverse the 6-OHDA-induced downregulation of total swimming distance in a zebrafish model of PD. Using a rat model of PD, we showed that a 6-OHDA-induced increase in the number of turns, and increased time spent by rats on the beam, could be reversed by 11-de treatment. Lastly, we showed that 6-OHDA-induced attenuation in tyrosine hydroxylase (TH), a dopaminergic neuronal marker, in zebrafish and rat models of PD could also be reversed by treatment with 11-de. Moreover, the patterns of DJ-1 expression observed in this study in the zebrafish and rat models of PD corroborated the trend noted in previous in vitro studies.