YTHDF2 regulates MSS51 expression contributing to mitochondria dysfunction of granulosa cells in polycystic ovarian syndrome patients.

RESEARCH QUESTION: Granulosa cells (GCs) dysfunction plays a crucial role in the pathogenesis of polycystic ovary syndrome (PCOS). It is reported that YTH domain-containing family protein 2 (YTHDF2) is upregulated in mural GCs of PCOS patients. What effect does the differential expression of YTHDF2 have in PCOS patients? DESIGN: Mural GCs and cumulus GCs from 15 patients with PCOS and 15 ovulatory controls and 4 cases of pathological sections in each group were collected. Real-time PCR, Western Blot, immunohistochemistry, and immunofluorescence experiments were conducted to detect gene and protein expression. RNA immunoprecipitation assay was performed to evaluate the binding relationship between YTHDF2 and MSS51. Mitochondrial morphology, cellular ATP and ROS levels and glycolysis-related gene expression were detected after YTHDF2 overexpression or MSS51 inhibition. RESULTS: In the present study, we found that YTHDF2 was upregulated in GCs of PCOS patients while MSS51 was downregulated. YTHDF2 protein can bind to MSS51 mRNA and affect MSS51 expression. The reduction of MSS51 expression or the increase in YTHDF2 expression can lead to mitochondrial damage, reduced ATP levels, increased ROS levels and reduced expression of LDHA, PFKP and PKM. CONCLUSIONS: YTHDF2 may regulate the expression of MSS51, affecting the structure and function of mitochondria in GCs and interfering with cellular glycolysis, which may disturb the normal biological processes of GCs and follicle development in PCOS patients.

The chromatographic fingerprinting study and genotoxicity evaluation of aqueous extract from Cyclocarya paliurus leaves.

Cyclocarya paliurus leaf is a medicinal and edible homologous plant, which possess various bioactive components with significant health benefits. However, the quality and safety of the aqueous extract from Cyclocarya paliurus leaves (CPLAE) vary greatly due to the raw materials and preparation technology. At present, chromatographic fingerprinting has been widely used for qualitative and quantitative analysis of traditional Chinese medicine (TCM). In this study, a method combining high performance liquid chromatography (HPLC) fingerprint with quantitative analysis was established and successfully applied to the characterization and quality evaluation of the CPLAE. In addition, the genetic safety of the CPLAE was evaluated by genotoxicity tests, including Ames test, chromosomal aberration test of Chinese hamster lung (CHL) cell in vitro, and bone marrow micronucleus test in mice. The results showed that 10 batches of CPLAE samples were analyzed by high performance liquid chromatography coupled with mass spectrometry (HPLC-MS), and the similarity of chromatographic fingerprint of each batch was above 0.961, indicating good similarity. At the same time, the 6 compounds with high absorption strength in the chromatogram were quantitatively analyzed. The results showed that all 6 compounds had good regression (R2=1.000) in the test range, and the recoveries ranged from 96.25% to 102.46%. The results of the 3 genotoxicity tests showed that the highest dose of CPLAE had no genotoxicity. In conclusion, the newly established chromatographic fingerprint and multi-component quantitative analysis method is stable and accurate, and can be used for the identification and quality evaluation of the CPLAE. Moreover, the CPLAE has the characteristics of safety and high quality as functional materials in food.

Effective protection: the embryonic development and clinical outcomes of emergency vitrification of 1246 oocytes and Day 0-Day 5 embryos in a natural disaster.

STUDY QUESTION: Can emergency vitrification protect embryos and oocytes during natural disasters or other events that prevent normal practice to achieve satisfactory embryonic development and clinical outcomes at a later time? SUMMARY ANSWER: Emergency vitrification of oocytes and Day 0-Day 5 (D0-D5) embryos during disasters is a safe and effective protective measure. WHAT IS KNOWN ALREADY: When some destructive events such as floods, earthquakes, tsunamis, and other accidents occur, emergency vitrification in embryo laboratories to protect human embryos, oocytes, and sperm is one of the important measures of an IVF emergency plan. However, there are few detailed reports on emergency vitrification in a state of disaster, especially about oocytes and D0 zygotes. Therefore, the effectiveness and safety of emergency vitrification of oocytes and D0-D5 embryos in disaster states are still unclear. STUDY DESIGN, SIZE, DURATION: A retrospective study was made in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from January 2018 to November 2022. The record rainstorms in Zhengzhou, China, caused severe flooding, traffic disruptions, and power outages. From 17:30, 20 July 2021 to 17:30, 21 July 2021, 1246 oocytes and D0-D5 embryos of 155 patients were vitrified whilst the laboratory had only an emergency power supply. PARTICIPANTS/MATERIALS, SETTING, METHODS: As of 21 December 2021, 1149 emergency vitrified oocytes and D0-D5 embryos of 124 patients underwent frozen-thawed embryo transfer (FET). They were divided into the following four groups according to the days of embryo culture in vitro: oocyte group, Day 0-Day 1 (D0-D1) group, Day 2-Day 3 (D2-D3) group, and Day 4-Day 5 (D4-D5) group. Control groups for each were selected from fresh cycle patients who underwent IVF/ICSI from January 2018 to October 2021. Control and emergency vitrification patients were matched on criteria that included age, fertilization method, days of embryonic development, and number and grade of transferred embryos. A total of 493 control patients were randomly selected from the eligible patients and matched with the emergency vitrification groups in a ratio of 4:1. The results of assisted reproduction and follow-up of pregnancy were analyzed. The embryonic development, clinical outcomes, and birth outcomes in each group were statistically analyzed. MAIN RESULTS AND THE ROLE OF CHANCE: A significant difference was observed in fertilization rate (81% versus 72%, P = 0.022) between the oocyte group and the control group. Significant differences were also observed in the monozygotic twin pregnancy rate (10% versus 0%, P = 0.038) and ectopic pregnancy rate (5% versus 0%, P = 0.039) between the D0-D1 group and the control group. No significant differences (P > 0.05) were observed between vitrified oocytes/D0-D1 embryos/D2-D3 embryos and the control group on the number of high-quality embryos (3.17 ± 3.00 versus 3.84 ± 3.01, P = 0.346; 5.04 ± 3.66 versus 4.56 ± 2.87, P = 0.346; 4.85 ± 5.36 versus 5.04 ± 4.64, P = 0.839), the number of usable blastocysts (1.22 ± 1.78 versus 1.21 ± 2.03, P = 0.981; 2.16 ± 2.26 versus 1.55 ± 2.08, P = 0.090; 2.82 ± 3.23 versus 2.58 ± 3.32, P = 0.706), clinical pregnancy rate (56% versus 57%, P = 0.915; 55% versus 55%, P = 1.000; 40% versus 50%, P = 0.488), miscarriage rate (30% versus 15%, P = 0.496; 5% versus 11%, P = 0.678; 17% versus 20%, P = 1.000), and live birth rate (39% versus 49%, P = 0.460; 53% versus 50%, P = 0.772; 33% versus 40%, P = 0.635). No significant differences (P > 0.05) were observed between the D4-D5 group and the control group on clinical pregnancy rate (40% versus 55%, P = 0.645), miscarriage rate (0% versus 18%, P = 1.000), and live birth rate (40% versus 45%, P = 1.000). LIMITATIONS, REASONS FOR CAUTION: The retrospective study design is a limitation. The timing and extent of natural disasters are unpredictable, so the sample size of vitrified oocytes, zygotes, and embryos is beyond experimental control. WIDER IMPLICATIONS OF THE FINDINGS: This study is the first study analyzing embryonic development, clinical outcomes, and birth outcomes of large samples of oocytes, D0 zygotes, and D1-D5 embryos after emergency vitrification under the disaster conditions. The results show that emergency vitrification is a safe and effective protective measure applicable to oocytes and D0-D5 embryos. The embryology laboratories need to be equipped with an emergency uninterrupted power supply capable of delivering for 6-8 h at full load. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the National Natural Science Foundation of China (grant 81871206). The authors declare that they have no conflicts of interest. All authors have completed the ICMJE Disclosure form. TRIAL REGISTRATION NUMBER: N/A.

The protective effects and mechanism of Ruyi Zhenbao Pill, a Tibetan medicinal compound, in a rat model of osteoarthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruyi Zhenbao Pill (RZP) is a prescribed Tibetan formulation for the treatment of white-pulse-disease, yellow-water-disease as well as pain-related disease. RZP is composed of 30 medicinal materials including herbal medicine, animal medicine and mineral medicine. They are widely used in the Tibetan area to treat cerebrovascular disease, hemiplegia, rheumatism, and pain diseases for centuries. AIM OF THE STUDY: The aim of the present study was to evaluate the anti-osteoarthritis function of RZP and to clarify the underlying mechanisms. MATERIALS AND METHODS: The active components in RZP were identified using HPLC methods. Osteoarthritis (OA) animal model was established via intra-articular injection of papain in rat knees. After the administration of RZP (0.45, 0.9 g/kg) for 28 days, the clinical observation was conducted, and pathological changes as well as serum biochemical indexes were detected. Moreover, therapeutic targets and pathways of RZP were discussed. RESULTS: The results showed that RZP could suppress knee joint swelling and arthralgia, thus relieving joint pain and inflammation in OA rats. Microcomputed tomography (µCT)-based physiological imaging and staining pictures confirmed the therapeutic effects of RZP on OA symptoms including knee joint swelling and structural changes with progressive inflammation in OA rats. RZP could promote the synthesis or inhibit the degradation of COLⅡ, attenuate OA-induced OPN up-regulation and thus relieve the OA symptom. Furthermore, RZP (0.45-0.9 g/kg) could all ameliorate the imbalance of biomarkers related to OA such as MMP1, TNF-α, COX2, IL-1ß and iNOS in knee joints or serum. CONCLUSION: In conclusion, RZP could effectively relieve inflammatory reaction induced by OA injury and the formulation could be applied to the treatment of OA therapy.

Synthesis of Carbon Dots with Hemostatic Effects Using Traditional Chinese Medicine as a Biomass Carbon Source.

As novel nanomaterials developed gradually with nanotechnology, carbon dots have been widely applied in medical applications, including disease treatment, drug delivery, antibacterial applications, and phototherapy. Based on the similar process between Chinese medicinal materials for hemostasis and modern carbon dots, this paper reports the preparation of four luminescent carbon dots with Chinese medicinal materials (plants and animals) as carbon sources and the investigation on their hemostatic effects in vitro and in rat bleeding models. It is found that the four studied carbon dots exhibit similar hemostatic effects and hemostatic mechanisms through impacting both endogenous and exogenous coagulation pathways. In addition, these carbon dots all exhibit anti-inflammatory effects and good biocompatibility, ensuring their potential in pretraumatic fields. This work provides a new perspective for hemostatic carbon dots prepared using carbonized natural plants and animals and new ideas for the research of new hemostatic materials.

[Analysis of the principles of Tibetan medicine processing].

Tibetan medicine processing ensures the safety of clinical application of Tibetan medicine. It is of great significance to analyze the principles of Tibetan medicine processing in the development, inheritance, and innovation of Tibetan medicine. However, due to the late start of modern Tibetan medicine research and the disciplinary division, the current research on Tibetan medicine processing focuses on the exploration and collation of traditional techniques and the analysis of the processing mechanism of Tibetan medicine through chemical and pharmacological research, but its principles and traditional theories have been rarely reported. In view of this, after analyzing the concept, essence, theories, purposes, and functions of Tibetan medicine processing through the integration of Tibetan medicine, Tibetan pharmacology, and clinical research of Tibetan medicine, this study proposed that the essence of Tibetan medicine processing was to change the "five sources" composition of medicinal materials through physical, chemical, and biological means, or the comprehensive means, and the theoretical principle of Tibetan medicine processing was to change or transform the positive and adverse effects or the obvious and recessive effects by altering the "five sources" composition of the drug to maximize the positive effect and minimize the adverse effect and the damage to the body, thereby achieving the purposes of toxicity reduction, efficacy enhancement, and drug property harmonization represented by sharpening, softening, nourishing, and reasonable compatibility. This study is expected to provide references for the construction of the theoretical system of Tibetan medicine processing, the inheritance of processing techniques, and innovative research.

The fluorescence mechanism of carbon dots based on the separation and identification of small molecular fluorophores.

Carbon dots (CDs) have attracted much attention in theoretical researches and their practical applications due to their excellent optical properties, and many researchers discovered that flurophores play a very important role in synthesis process of CDs and the luminescence of prepared CDs. In this study, two CDs were pyrolysis with citric acid, N-acetyl-l-cysteine and glutathione derivatives as carbon sources. Four intermediate small molecules were separated from the prepared CDs through ultrafiltration and chromatography, and their chemical structures were determined. The formation process of CDs was monitored through identified small molecule intermediates and HPLC. It is speculated that the two CDs have the same formation pathway, including TPA (5-oxo-2,3-dihydro-5H-[1,3]thiazolo[3,2-a]pyridine-3,7-dicarboxylic acid) synthesis, fluorophore polymerization, carbon chain extension, and carbonization. It was also discovered that these two CDs have the same fluorescence properties, thiazolopyridone structure, and nitrogen-sulfur co-doped functional groups are important reasons for the mixed excitation dependence of CDs. This study would provide valuable theoretical basis for the studies on preparation of excellent CDs, raw material selection, and CDs formation mechanism.

Mongolian Medicine Areca Thirteen Pill (GY-13) Improved Depressive Syndrome via upregulating cAMP/PKA/CREB/BDNF signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Areca Thirteen Pill, also called Gao You-13 (GY-13), is a traditional Mongolian herbal formula and has been extensively used to treat depression in Mongolian areas, which belongs to Heyi disease in Mongolian medicine. Major depressive disorder is a serious psychiatric disease, only one-third of individuals with depression are responsive to current antidepressants in clinic. Growing attention has been attracted by traditional herbal medicines in fighting depression because they are considered safer alternatives to pharmacotherapy. AIM OF THE STUDY: To reveal the mechanism of GY-13 in the treatment of depression. MATERIALS AND METHODS: The rat depression model was established by chronic unpredictable mild stress (CUMS), and primary hippocampal neurons were used to construct a glutamate-induced excitotoxicity model. The antidepressant effect of GY-13 was then assessed by performing sucrose preference tests, open field tests, and body weight measurements on rats. The expression of cAMP and PKA, mRNA levels of brain-derived neurotrophic factor (BDNF) and cAMP response element binding protein (CREB), and hippocampal neuronal apoptosis were measured. RESULTS: The results indicate that GY-13 significantly improves depression-like behavior, rescues decreased cAMP， PKA, recovers the mRNA levels of CREB and BDNF, and increases the proliferative activity of hippocampus. In addition, blockade of PKA reverses the effects of GY-13 treatment on CREB mRNA, BDNF mRNA levels. In vitro, GY-13 treatment increased hippocampal proliferative activity and attenuated Glu-induced apoptosis of hippocampal neurons as well as reduced CREB mRNA and BDNF mRNA expression levels. CONCLUSIONS: Our research demonstrated that GY-13 treatment exerted a potent antidepressant action via activation of cAMP/CREB/BDNF signaling pathway, promoting proliferation, and suppressing apoptosis. This research provides molecular biological ground for developing GY-13 into a potent alternative for the intervention of depression.

Screening of Chitosan Derivatives-Carbon Dots Based on Antibacterial Activity and Application in Anti-Staphylococcus aureus Biofilm.

Introduction: Pathogenic bacteria, especially the ones with highly organized, systematic aggregating bacteria biofilm, would cause great harm to human health. The development of highly efficient antibacterial and antibiofilm functional fluorescent nanomaterial would be of great significance. Methods: This paper reports the preparation of a series of antibacterial functional carbon dots (CDs) with chitosan (CS) and its derivatives as raw materials through one-step route, and the impact of various experiment parameters upon the optical properties and the antibacterial abilities have been explored, including the structures of the raw materials, excipients, and solvents. Results: The CDs prepared by quaternary ammonium salt of chitosan (QCS) and ethylenediamine (EDA) exhibit multiple antibacterial effects through membrane breaking, DNA and protein destroying, and the production of singlet oxygen. The CDs showed excellent broad-spectrum inhibitory activity against a variety of bacteria (Gram-positive and negative bacteria), in particular, to the biofilm of Staphylococcus aureus with minimum inhibitory concentration at 10 µg/mL, showing great potential in killing bacteria and biofilms. The biocompatibility experiments proved that QCS-EDA-CDs are non-toxic to human normal hepatocytes and have low haemolytic effect. Furthermore, the prepared QCS-EDA-CDs have been successfully used in bacterial and biofilm imaging thanks to their excellent optical properties. Conclusion: This paper explored the preparation and application of functional CDs, which can be used as the visual probe and therapeutic agents in the treatment of infections caused by bacteria and biofilm.

Simultaneous determination of aesculin and aesculetin and their interactions with DNA using carbon fiber microelectrode modified by Pt-Au bimetallic nanoparticles.

Electrode sensitivity and selectivity in complex biological matrices are major challenges in the development of electrochemical sensors. Bimetallic nanoparticles provide a new perspective for enhancing electrocatalytic property because of some specific synergetic effects. In this work, platinum nanoparticles (PtNPs) and gold nanoparticles (AuNPs) modified carbon fiber microelectrode (PtNPs/AuNPs/CFME) was fabricated to determine aesculin and aesculetin simultaneously. Differential pulse voltammetry (DPV) method was conducted for the electrochemical sensing of aesculin and aesculetin, the modified electrode displayed high electrocatalytic activity for the redox of these two drugs. The linear ranges of aesculin and aesculetin were 0.4-10 µM and 0.04-1 µM, with the detection limits of 41 nM and 3.6 nM, respectively, which were the lowest values achieved. Furthermore, an electrochemical investigation of the interactions of these two drugs with Calf thymus double stranded DNA (dsDNA) was investigated by PtNPs/AuNPs/CFME, the decrease in peak currents is proportional to DNA concentration and can be used to detect DNA. The electrode was successfully used to measure aesculin and aesculetin in mouse serum and urine with 98.0-104.8% recovery. The novel electrochemical probe possessed excellent performances of high sensitivity, good reproducibility, and simplicity of fabrication, which will facilitate effective detection of aesculin and aesculetin for metabolic kinetics study.

The Extraction of ß-Carotene from Microalgae for Testing Their Health Benefits.

ß-carotene, a member of the carotenoid family, is a provitamin A, and can be converted into vitamin A (retinol), which plays essential roles in the regulation of physiological functions in animal bodies. Microalgae synthesize a variety of carotenoids including ß-carotene and are a rich source of natural ß-carotene. This has attracted the attention of researchers in academia and the biotech industry. Methods to enrich or purify ß-carotene from microalgae have been investigated, and experiments to understand the biological functions of microalgae products containing ß-carotene have been conducted. To better understand the use of microalgae to produce ß-carotene and other carotenoids, we have searched PubMed in August 2021 for the recent studies that are focused on microalgae carotenoid content, the extraction methods to produce ß-carotene from microalgae, and the bioactivities of ß-carotene from microalgae. Articles published in peer-reviewed scientific journals were identified, screened, and summarized here. So far, various types and amounts of carotenoids have been identified and extracted in different types of microalgae. Diverse methods have been developed overtime to extract ß-carotene efficiently and practically from microalgae for mass production. It appears that methods have been developed to simplify the steps and extract ß-carotene directly and efficiently. Multiple studies have shown that extracts or whole organism of microalgae containing ß-carotene have activities to promote lifespan in lab animals and reduce oxidative stress in culture cells, etc. Nevertheless, more studies are warranted to study the health benefits and functional mechanisms of ß-carotene in these microalgae extracts, which may benefit human and animal health in the future.

Anshen Buxin Liuwei Pill, a Mongolian Medicinal Formula, Could Protect H2O2-Induced H9c2 Myocardial Cell Injury by Suppressing Apoptosis, Calcium Channel Activation, and Oxidative Stress.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula which has a therapeutic effect on the symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and short breath. However, its bioactivity against cardiac injury remains unclear. METHODS: The protective effect of ABLP was evaluated using H9c2 cells. Cell viability, intracellular Ca2+, reactive oxidative indices, and mitochondrial membrane potential (∆ψ) were assessed, respectively. The mRNA levels of Ca2+ channel-related genes (DHPR, RyR2, and SCN5A) and oxidative stress-related genes (Keap1, Nrf2, and HO-1) were measured by RT-PCR. RESULTS: 0.5-50 µg/mL ABLP could significantly decrease H2O2-induced cell injury by suppressing cell necrosis/apoptosis and excess oxidative stress, ameliorating the collapse of ∆ψ, and reducing intracellular Ca2+ concentration. Furthermore, 0.5-50 µg/mL ABLP reversed H2O2-induced imbalance in the mRNA levels of DHPR, RyR2, SCN5A, Keap1, Nrf2, and HO-1 gene in H9c2 cells, which further illustrate the mechanism. CONCLUSION: ABLP provided protective and therapeutic benefits against H2O2-induced H9c2 cell injury, indicating that this formula can effectively treat coronary disease. In addition, the present study also provides an in-depth understanding of the pharmacological functions of ABLP, which may lead to further successful applications of Mongolian medicine.

Anshen-Buxin-Liuwei pill, a Mongolian medicinal formula could alleviate cardiomyocyte hypoxia/reoxygenation injury via mitochondrion pathway.

BACKGROUND: Anshen Buxin Liuwei pill (ABLP) is a Mongolian medicinal formula that is composed of six medicinal materials: the Mongolian medicine Bos taurus domesticus Gmelin, Choerospondias axillaris (Roxb.) Burtt et Hill, Myristica fragrans Houtt., Eugenia caryophµllata Thunb., Aucklandia lappa Decne., and Liqui dambar formosana Hance. ABLP is considered to have a therapeutic effect on symptoms such as coronary heart disease, angina pectoris, arrhythmia, depression and irritability, palpitation, and shortness of breath. METHODS: H9c2 cardiomyocytes were used to construct a hypoxia/reoxygenation (HR) injury model. CCK-8 assay and Annexin V-FITC cell apoptosis assays were used for cell viability and cell apoptosis determination. The LDH, SOD, MDA, CAT, CK, GSH-Px, Na+-K+-ATPase, and Ca2+-ATPase activities in cells were determined to assess the protective effects of ABLP. The mRNA levels of Sirtuin3 (Sirt3) and Cytochrome C (Cytc) in H9c2 cells were determined by quantitative real-time PCR. RESULTS: The results indicate that HR-treated cells began to shrink from the spindle in an irregular shape with some floated in the medium. By increasing the therapeutic dose of ABLP (5, 25, and 50 µg/mL), the cells gradually reconverted in a concentration-dependent manner. The release of CK in HR-treated cells was significantly increased, indicating that ABLP exerts a protective effect in H9c2 cells against HR injury and can improve mitochondrial energy metabolism and mitochondrial function integrity. The present study scrutinized the cardioprotective effects of ABLP against HR-induced H9c2 cell injury through antioxidant and mitochondrial pathways. CONCLUSIONS: ABLP could be a promising therapeutic drug for the treatment of myocardial ischemic cardiovascular disease. The results will provide reasonable information for the clinical use of ABLP.

Veratrilla baillonii Franch Ameliorates Diabetic Liver Injury by Alleviating Insulin Resistance in Rats.

Type 2 diabetes mellitus (T2DM) is a complex and polygenic disorder with diverse complications. Veratrilla baillonii Franch (V. baillonii) has been applied in the intervention and treatment a diverse range of diseases, including diabetes. In this study, we revealed that water extracts of V. baillonii (WVBF) can ameliorate liver injury and insulin resistance in T2DM rat model. To elucidate the anti-diabetic mechanisms of WVBF, we performed liver transcriptome analysis that displayed WVBF treatment significantly suppressed many gene expressions involved in insulin resistance. Furthermore, functional experiments showed that WVBF treatment reduced the pathological damages of liver and pancreas, which may be regulated by Foxo1, Sirt1, G6pc, c-Met, Irs1, Akt1, Pik3r1. These results indicated that WVBF improves diabetic liver injury and insulin resistance in diabetic rats. Therefore, this study demonstrated WVBF could be used as a promising therapeutic agent for intervention and treatment of diabetes.

Therapeutic Uses of Traditional Chinese Medicines Against COVID-19.

COVID-19 is a pandemic and a serious respiratory disorder that is caused by coronavirus. It has produced an outbreak of acute infectious pneumonia in China and afterward all around the world. There is not a single anti-viral drug, vaccine or any kind of treatment available for this fatal disease. There are only a few options available for symptomatic relief. Thus, in China, 85% of SARS-CoV-2 infected individuals have been treated with traditional Chinese medicines (TCM). Thus, this article focused on the previous kinds of literature regarding COVID-19 and its treatment with TCM along with its applications. SARS-CoV-2 and SARS-CoV showed similarity in genes, pathological processes, and epidemiology, so these can be treated with TCM. The proof regarding treatment of SARS-CoV with TCM explicitly shows the advantages of using TCM therapy for COVID-19. Present literature explains the mode of action and efficacy of TCM and elaborates on the natural compounds introduced to treat COVID-19.

The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.

A hormonal imbalance may disrupt the rigorously monitored cellular microenvironment by hampering the natural homeostatic mechanisms. The most common example of such hormonal glitch could be seen in obesity where the uprise in adipokine levels is in virtue of the expanding bulk of adipose tissue. Such aberrant endocrine signaling disrupts the regulation of cellular fate, rendering the cells to live in a tumor supportive microenvironment. Previously, it was believed that the adipokines support cancer proliferation and metastasis with no direct involvement in neoplastic transformations and tumorigenesis. However, the recent studies have reported discrete mechanisms that establish the direct involvement of adipokine signaling in tumorigenesis. Moreover, the individual adipokine profile of the patients has never been considered in the prognosis and staging of the disease. Hence, the present manuscript has focused on the reported extensive mechanisms that culminate the basis of poor prognosis and diminished survival rate in obese cancer patients.

Multifunctional Biomedical Applications of Nitrogen and Sulfur Co-Doped Carbon Dots.

Multifunctional carbon dots have drawn considerable attention due to their potential biomedical application value. We report the preparation of blue-green fluorescence-emitting, multifunctional, nitrogen-and-sulfur co-doped carbon dots (N, S-CDs) synthesized via a one-step process using 1-thioglycerol as a sulfur source, glucose and citric acid as carbon sources, and polyethyleneimine as a nitrogen source. Because of abundant amino and sulfur content, the CDs exhibited high sensibility and selectivity for detecting Cu2+ (detection limit: 0.01 µM, linear range: 0.025 to 50 µM). Fast and sensitive detection of tiopronin was also achieved on the basis of the fluorescence "off-on" mode considering the strong affinity between tiopronin and Cu2+. The N, S-CDs exhibited good biocompatibility as determined by fluorescence imaging using onion epidermal cells and gram-positive bacteria. The CDs also exhibited excellent antimicrobial ability against the gram-positive bacteria. Our results indicate that these novel N, S-CDs could be ideal candidates for several biochemical applications such as antibacterial treatment and detection of small biomolecules.

An Exploration of Knowledge, Attitude, and Practices of Physicians toward Pharmacovigilance at Tertiary Care Hospitals in Khyber-Pakhtunkhwa Province, Pakistan.

Drug safety assures the effectiveness, safety, and security of drugs, vaccines, and other biologicals to protect public health. Medication-related errors coupled with unjudicial medication practices often cause a catastrophic impact on the healthcare system globally. The present study aimed to assess the knowledge, attitude, and practice of physicians toward pharmacovigilance and barriers to adverse drug reaction (ADR) reporting at tertiary care hospitals in Khyber-Pakhtunkhwa (KP) province, Pakistan. A descriptive cross-sectional study was conducted among registered doctors working in seven tertiary care hospitals from seven administrative divisions of KP province of Pakistan from July 2019 to March 2020. During the study period, 358 physicians who fulfilled the inclusion criteria and agreed to participate completed and returned the validated structured questionnaires. Descriptive and inferential statistics were applied for data analysis. The majority of physicians had poor knowledge (81.3%) regarding pharmacovigilance along with poor reporting practices (94.9%), although (96.5%) had a positive attitude toward ADR reporting. A significant barrier identified was the unavailability of reporting forms (95.9%), whereas mandatory ADR reporting (96.2%) was the major factor to encourage ADR reporting. Physicians aged ≥ 41 and experience ≥ 11 years had significantly more knowledge than other categories (P < 0.001). Significant association (P < 0.001) of physicians' knowledge and practice were found where 77.2% of the participants having poor knowledge reported poor practices. Physicians' understanding of pharmacovigilance was suboptimal, although they have a positive attitude toward ADR reporting. Thus, there is a need for continuous education and training programs to support pharmacovigilance activities that could improve physicians' understanding.

Comparison of Chemical Constituents and Pharmacological Effects of Different Varieties of Chrysanthemum Flos in China.

Chrysanthemum Flos is the prestigious traditional Chinese medicinal material and the popular health drink. This article comprehensively evaluated the chemical constituents, antioxidant activity, and hepatoprotective effects of 25 common chrysanthemum varieties in China. Firstly, we analyzed the chemical compositions of water extracts of chrysanthemum using UPLC/Q-TOF-MS, and identified 29 chemical components. The results displayed that chrysanthemum was rich in chemical constituents, but there were significant differences in the contents of four phenolic acids and five flavonoids among different varieties, and the coefficient of variation (CVs) ranged from 35.96 % to 114.62 %. Then, the antioxidant activities of different chrysanthemums were investigated, respectively via 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), and Ferric Reducing Antioxidant Power (FRAP) assays. The spectrum-effect relationships between nine main components and antioxidant activities were investigated to identify the antioxidant constitutes in chrysanthemums. Meanwhile, H2 O2 -induced hepatocyte injury testing showed wide variation in cultivar antioxidant capacity, with Tongchengju (TCJ) producing the best effect (90.32 %), followed by Chuju (CJ; 85.78 %). In addition, the hepatoprotective effects of 8 mainstream varieties were determined by the model of acute alcoholic liver injury. They protected liver from injury by affecting relevant liver function and antioxidant indexes. Huangshangongju (HSG) could decrease aspartate aminotransferase (AST) activity by 39.27 % in liver tissue; Hangju-Fubaiju (HJ-FBJ), Jinsihuangju (JSH), and Chuju (CJ) significantly decreased the malondialdehyde (MDA) content of liver tissue, which reduced by more than 40 %; Jinsihuangju (JSH) of used for tea could double the content of glutathione (GSH) and had the similar effect on superoxide dismutase (SOD) as the positive group, showing significant antioxidant capacity. Therefore, this study confirmed that chrysanthemums are potential resources as antioxidants, functional foods, and medicinal materials. Importantly, it may provide a scientific support for further development and utilization of chrysanthemum, and screen excellent varieties for different demands.

Systems pharmacology-based dissection of mechanisms of Tibetan medicinal compound Ruteng as an effective treatment for collagen-induced arthritis rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Compound Ruteng (CRT) is a prescribed formulation based on the theory of Tibetan medicine for the treatment of yellow-water-disease. It is consisted with 7 medicinal material include Boswellia carterii Birdw (named "Ruxiang" in Chinese); Tinospora sinensis (Lour.) Merr. (named "Kuan-Jin-Teng" in Chinese), Cassia obtusifolia L (named "Jue-Ming-Zi" in Chinese); Abelmoschus manihot (L.) Medic (named "Huang-Kui-Zi" in Chinese); Terminalia chebula Retz. (named "He-Zi" in Chinese); Lamiophlomis rotata (Benth.) Kudo (named "Du-Yi-Wei" in Chinese) and Pyrethrum tatsienense (Bur. et Franch.) Ling (named "Da-Jian-Ju" in Chinese). They are widely distributed in Tibet area of China and have been used to treat rheumatism, jaundice, and skin diseases for centuries. AIM OF THE STUDY: The present study was conducted to investigate the anti-arthritis effect of CRT and to disclose the systems pharmacology-based dissection of mechanisms. MATERIALS AND METHODS: The chemical constituents in CRT were identified using HPLC method, and CRT candidate targets against RA were screened by network pharmacology-based analysis and further experimentally validated based on collagen-induced arthritis (CIA) rat model. Furthermore, therapeutic mechanisms and pathways of CRT were investigated. RESULTS: 391 potential targets (protein) were predicted against 92 active ingredients of 7 medicinal materials in CRT. Enrichment analysis and molecular docking studies also enforced the practiced results. X-ray based physiological imaging showed the attenuated effect of CRT on paw swelling, synovial joints and cartilage with improved inflammation in CIA rats. Moreover, the expression of biomarkers associated with RA such as MMP1, MMP3 and MMP13 and TNF-a, COX2 and iNOS are down-regulated in ankle joints, serum, or liver. CONCLUSION: In conclusion, CRT compound could attenuate RA symptoms and active ingredients of this compound could be considered for drug designing to treat RA.