Molecular Mechanisms of Medicinal Plant Securinega Suffruticosa-derived Compound Securinine against Spinal Muscular Atrophy based on Network Pharmacology and Experimental Verification.

BACKGROUND: Spinal Muscular Atrophy (SMA) is a severe motor neuronal disorder with high morbidity and mortality. Securinine has shown the potential to treat SMA; however, its anti-SMA role remains unclear. OBJECTIVE: This study aims to reveal the anti-SMA mechanisms of securinine. METHODS: Securinine-associated targets were acquired from Herbal Ingredients' Targets (HIT), Similarity Ensemble Approach (SEA), and SuperPred. SMA-associated targets were obtained from GeneCards and Dis- GeNET. Protein-protein interaction (PPI) network was constructed using GeneMANIA, and hug targets were screened using cytoHubba. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using ClusterProfifiler. Molecular docking was conducted using Pymol and Auto- Dock. In vitro assays were used to verify the anti-SMA effects of securinine. RESULTS: Twenty-six intersection targets of securinine and SMA were obtained. HDAC1, HDAC2, TOP2A, PIK3R1, PRMT5, JAK2, HSP90AB1, TERT, PTGS2, and PAX8 were the core targets in PPI network. GO analysis demonstrated that the intersecting targets were implicated in the regulation of proteins, steroid hormones, histone deacetylases, and DNA transcription. KEGG analysis, pathway-pathway, and hub target-pathway networks revealed that securinine might treat SMA through TNF, JAK-STAT, Ras, and PI3K-Akt pathways. Securinine had a favorable binding affinity with HDAC1, HSP90AB, JAK2, PRMT5, PTGS2, and TERT. Securinine rescued viability suppression, mitochondria damage, and SMN loss in the SMA cell model. Furthermore, securinine increased HDAC1 and PRMT5 expression, decreased PTGS2 expression, suppressed the JAK2-STAT3 pathway, and promoted the PI3K-Akt pathway. CONCLUSION: Securinine might alleviate SMA by elevating HDAC1 and PRMT5 expression and reducing PTGS2 via JAK2-STAT3 suppression and PI3K-Akt activation.

Indole Propionic Acid Disturbs the Normal Function of Tryptophanyl-tRNA Synthetase in Mycobacterium tuberculosis.

Tuberculosis (TB) is the leading infectious disease caused by Mycobacterium tuberculosis and the second-most contagious killer after COVID-19. The emergence of drug-resistant TB has caused a great need to identify and develop new anti-TB drugs with novel targets. Indole propionic acid (IPA), a structural analog of tryptophan (Trp), is active against M. tuberculosis in vitro and in vivo. It has been verified that IPA exerts its antimicrobial effect by mimicking Trp as an allosteric inhibitor of TrpE, which is the first enzyme in the Trp synthesis pathway of M. tuberculosis. However, other Trp structural analogs, such as indolmycin, also target tryptophanyl-tRNA synthetase (TrpRS), which has two functions in bacteria: synthesis of tryptophanyl-AMP by catalyzing ATP + Trp and producing Trp-tRNATrp by transferring Trp to tRNATrp. So, we speculate that IPA may also target TrpRS. In this study, we found that IPA can dock into the Trp binding pocket of M. tuberculosis TrpRS (TrpRSMtb), which was further confirmed by isothermal titration calorimetry (ITC) assay. The biochemical analysis proved that TrpRS can catalyze the reaction between IPA and ATP to generate pyrophosphate (PPi) without Trp as a substrate. Overexpression of wild-type trpS in M. tuberculosis increased the MIC of IPA to 32-fold, and knock-down trpS in Mycolicibacterium smegmatis made it more sensitive to IPA. The supplementation of Trp in the medium abrogated the inhibition of M. tuberculosis by IPA. We demonstrated that IPA can interfere with the function of TrpRS by mimicking Trp, thereby impeding protein synthesis and exerting its anti-TB effect.

Brain nuclei and neural circuits in neuropathic pain and brain modulation mechanisms of acupuncture: a review on animal-based experimental research.

Neuropathic pain (NP) is known to be associated with abnormal changes in specific brain regions, but the complex neural network behind it is vast and complex and lacks a systematic summary. With the help of various animal models of NP, a literature search on NP brain regions and circuits revealed that the related brain nuclei included the periaqueductal gray (PAG), lateral habenula (LHb), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC); the related brain circuits included the PAG-LHb and mPFC-ACC. Moreover, acupuncture and injurious information can affect different brain regions and influence brain functions via multiple aspects to play an analgesic role and improve synaptic plasticity by regulating the morphology and structure of brain synapses and the expression of synapse-related proteins; maintain the balance of excitatory and inhibitory neurons by regulating the secretion of glutamate, γ-aminobutyric acid, 5-hydroxytryptamine, and other neurotransmitters and receptors in the brain tissues; inhibit the overactivation of glial cells and reduce the release of pro-inflammatory mediators such as interleukins to reduce neuroinflammation in brain regions; maintain homeostasis of glucose metabolism and regulate the metabolic connections in the brain; and play a role in analgesia through the mediation of signaling pathways and signal transduction molecules. These factors help to deepen the understanding of NP brain circuits and the brain mechanisms of acupuncture analgesia.

Clinical significance of the expression levels of serum transforming growth factor-ß and CXC type chemokine ligand 13 in primary Sjogren's syndrome patients.

OBJECTIVE: The aim of this study was to investigate the expression levels of the serum transforming growth factor-ß1 (TGF-ß1) CXC type chemokine ligand 13 (CXCL13) in primary Sjogren's syndrome (pSS) patients and its correlation with disease severity. METHOD: Thirty patients with pSS admitted to Nanjing Traditional Chinese Medicine Affiliated Hospital of Nanjing University of Traditional Chinese Medicine from January 2021 to December 2022 were included as the pSS group, while 30 patients who underwent physical examination during the same period were included as the control group. The levels of TGF-ß1 and CXCL13 were detected. The diagnostic value of TGF-ß1 and CXCL13 for pSS was analyzed. Detection of serum TGF-ß1 and CXCL13 levels in pSS patients with different disease activities and lip gland pathological grading of pSS was done. We compared the correlation between TGF-ß1 and CXCL13 levels and disease activity and labial gland pathological grading in pSS patients. RESULT: The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. The area under the receiver operating characteristic (ROC) curve (AUC) for TGF-ß1 and CXCL13 diagnosis of pSS was 0.790 (95% confidence interval (CI): 0.720~0.861) and 0.838 (95% CI: 0.778~0.898), respectively. The serum TGF-ß1 and CXCL13 levels of pSS patients significantly increase with the increase of disease activity and lip gland pathological grading. The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. CONCLUSION: The levels of TGF-ß1 and CXCL13 in pSS patients were increased, and it was closely related to disease activity and lip gland pathological grading, which can be used as an effective indicator for the diagnosis of pSS. Key Points • The TGF-ß1 and CXCL13 levels in the pSS group were higher than those in the control group. • The TGF-ß1 and CXCL13 levels in pSS patients were positively correlated with disease activity and lip gland pathological grading. • TGF-ß1 and CXCL13 can be used as an effective indicator for the diagnosis of pSS.

Electrochemical molecular intercalation and exfoliation of solution-processable two-dimensional crystals.

Electrochemical molecular intercalation of layered semiconducting crystals with organic cations followed by ultrasonic exfoliation has proven to be an effective approach to producing a rich family of organic/inorganic hybrid superlattices and high-quality, solution-processable 2D semiconductors. A traditional method for exfoliating 2D crystals relies on the intercalation of inorganic alkali metal cations. The organic cations (e.g., alkyl chain-substituted quaternary ammonium cations) are much larger than their inorganic counterparts, and the bulky molecular structure endows distinct intercalation and exfoliation chemistry, as well as molecular tunability. By using this protocol, many layered 2D crystals (including graphene, black phosphorus and versatile metal chalcogenides) can be electrochemically intercalated with organic quaternary alkylammonium cations. Subsequent solution-phase exfoliation of the intercalated compounds is realized by regular bath sonication for a short period (5-30 min) to produce free-standing, thin 2D nanosheets. It is also possible to graft additional ligands on the nanosheet surface. The thickness of the exfoliated nanosheets can be measured by using atomic force microscopy and Raman spectroscopy. Modifying the chemical structure and geometrical configuration of alkylammonium cations results in different exfoliation behavior and a family of versatile organic/inorganic hybrid superlattices with tunable physical/chemical properties. The whole protocol takes ~6 h for the successful production of stable, ultrathin 2D nanosheet dispersion in solution and another 11 h for depositing thin films and transferring them onto an arbitrary surface. This protocol does not require expertise beyond basic electrochemistry knowledge and conventional colloidal nanocrystal synthesis and processing.

Association between caffeine consumption and bone mineral density in children and adolescent: Observational and Mendelian randomization study.

BACKGROUND: Coffee is the most commonly consumed beverage among children and adolescences. Caffeine was demonstrated to be associated with bone metabolism. However, the relationship between caffeine intake and BMD in children and adolescents remains unclear. This study aimed to identified relationship between caffeine consumption and bone mineral density (BMD) in children and adolescents. METHODS: Based on National Health and Nutrition Examination Survey (NHANES), we conducted an epidemiological cross-section study to measure the relationship between caffeine consumption and BMD in children and adolescents by multivariate linear regression models. Then, five methods of Mendelian randomization (MR) analyses were performed to estimate their causal relationship between coffee and caffeine intake and BMD in children and adolescents. MR-Egger and inverse-variance weighted (IVW) were used to evaluate the heterogeneity effect of instrumental variables (IVs). RESULTS: In epidemiological studies, individuals with the highest quartile of caffeine intake do not have a significant change in femur neck BMD (ß = 0.0016, 95% CI: -0.0096, 0.0129, P = 0.7747), total femur BMD (ß = 0.0019, P = 0.7552), and total spine BMD (ß = 0.0081, P = 0.1945) compared with the lowest quartile. In MR analysis, the IVW-random effect indicates no causal relationship between coffee consumption and TB- BMD (ß = 0.0034, P = 0.0910). Other methods of MR analyses and sensitivity analysis reveals consistent findings. Similarly, the fixed-effects IVW method shows no causal association between caffeine intake and TB-BMD in children and adolescents (ß = 0.0202, P = 0.7828). CONCLUSIONS: Our study does not support a causal relationship between caffeine consumption and BMD in children and adolescents. However, more studies are needed to verify our findings, such as its underlying molecular mechanisms and the long-term impact of early caffeine exposure at a younger age.

Undescribed amino acid-sesquiterpene lactone adducts and sesquiterpene glycosides from the roots of Saussurea lappa and their anti-HBV activity.

Saussurea lappa (Asteraceae family), a traditional Chinese medicine, has been found to possess anti-inflammatory, immune-promoting, antibacterial, antitumor, anti-HBV, cholestatic, and hepatoprotective activities. Herein, two undescribed amino acid-sesquiterpene lactone adducts, saussureamines G and H (1 and 2), and two new sesquiterpene glycosides, saussunosids F and G (3 and 4), along with 26 known sesquiterpenoids (5-30) have been isolated from the roots of S. lappa. Their structures and absolute configurations of these compounds were established by physical data analyses such as HRESIMS, IR, 1D and 2D NMR and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (5, 6, 12, 13, 17, 19, 23, 26, 29, and 30) exhibited activities against the secretions of HBsAg and HBeAg. In particular, compound 6 showed inhibition of HBsAg and HBeAg secretion with IC50 values of 11.24 and 15.12 µM, with SI values of 1.25 and 0.93, respectively. Molecular docking studies were also conducted on the anti-HBV compounds. Overall, this study provides insights into the potential therapeutic uses of the compounds found in the roots of S. lappa, particularly in the treatment of hepatitis B virus infections.

Auricular therapy for primary dysmenorrhea: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Primary dysmenorrhea (PD) is a common problem among women. It is defined as any degree of perceived cramping pain during menstruation without any evident pathology. Auricular therapy (AT), a widely used alternative medical treatment method as part of traditional Chinese acupuncture, lacks reliable evidence to support its safety and effectiveness for PD. We aimed to conduct a meta-analysis to investigate the efficacy and safety of AT in PD and to investigate possible factors impacting the particular efficacy of AT in PD by meta-regression. METHODS: This protocol followed the PRISMA guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols. The following 9 sources will be searched for randomized control trials of AT for PD: the Cochrane Central Register of Controlled Trials, PubMed, Medline, Embase, Web of Science, Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure, Chinese Science and Technology Periodicals (VIP) database and WanFang Database from inception to January 1, 2023. Primary outcomes include visual rating scales and clinical efficacy rates, while secondary outcomes include endocrine hormone indicators related to PD and adverse events. Two reviewers will work independently on study selection, data extraction, and coding, including the risk of bias assessment in the included studies. While conducting a meta-analysis, Review Manager version 5.3 will be employed. Otherwise, a descriptive analysis will be performed. The results will be displayed as a risk ratio with 95% confidence intervals for dichotomous data as well as weight mean difference or standardized mean difference with 95% confidence intervals for continuous data. RESULTS: This study's protocol will investigate the efficacy and safety of AT in the treatment of PD in a systematic way. CONCLUSION: This systematic evaluation will objectively and systematically assess the efficacy and safety of AT in PD based on the available evidence, as well as provides clinicians with evidence to support the treatment of the disease.

Improvement influenza vaccine immune responses with traditional Chinese medicine and its active ingredients.

The current influenza vaccines are unable to provide effective protection in many cases, like influenza viruses strain antigenic drift or shift, and the influenza continues to cause significant annual morbidity and mortality. Improving the immune response to influenza vaccination is an unmet need. Traditional Chinese medicine (TCM) and its active ingredients are commonly known to have immunomodulatory properties. We therefore compared influenza vaccination alone or formulated with Astragali Radix (Huangqi in Chinese), and several representative ingredients of TCM, including lentinan (polysaccharide), panax notoginseng saponins (saponin), breviscapine (flavone), andrographolide (terpenoid), and a Chinese herbal compound (kangai) for their potential to enhance immune responses to influenza vaccine in mice. We found that all these TCM-adjuvants were able to increase hemagglutination inhibition (HAI) antibody titers, splenocyte proliferation, splenic T cell differentiation, bone marrow dendritic cell maturity, and both Th1 and Th2 cytokine secretion of influenza vaccine to varying degrees, and that had the characteristics of no excessive inflammatory responses and bidirectional regulation simultaneously. Taken together, our findings show that Astragali Radix exerts a more comprehensive effect on vaccine immunity, on both innate and adaptive immunity. The effects of lentinan and andrographolide on adaptive immunity were more significant, while the effects of breviscapine on innate immunity were stronger, and the other two TCM adjuvants were weaker. As the first report of a comprehensive evaluation of TCM adjuvants in influenza vaccines, the results suggest that TCM and their active ingredients are good candidates for enhancing the immune response of influenza vaccines, and that suitable TCMs can be selected based on the adjuvant requirements of different vaccines.

Biodegradable thermoset poly(lactic acid) resin containing phosphorus: Flame retardancy, mechanical properties and its soil degradation behavior.

With the growing environmental awareness, poly(lactic acid) (PLA) is regarded as one of the most promising varieties of bio-based polyesters owing to its environment-friendly and biodegradable advantages. However, poor thermal stability and flammability disadvantages limit the applications of PLA. Herein, a series of biodegradable intrinsic flame-retardant thermoset PLA resins (DMMP-M4sPLA) were designed. DMMP-M4sPLA resins exhibit excellent flame retardancy, achieving UL 94 V-0 rating and limiting oxygen index (LOI) of 28.1 %-31.7 %. Meanwhile, the cured DMMP-M4sPLA resins show a high glass transition temperature and tensile strength. In addition, the resins demonstrate full degradation with no harmful degradation products. This work provides an advanced design strategy to create bio-based and biodegraded resins with superior flame retardant and mechanical performance, holding great potentials in the fields of aviation interior, automotive, etc.

Mitochondrial dysfunction in a rat model and the related risk of metabolic disorders.

OBJECTIVE: To explore whether kidney deficiency (KYD) is prone to metabolic disorders may be linked to impaired mitochondrial function in thermogenesis and metabolic tissues. METHODS: A rat model of KYD was used, which was established using Sprague Dawley rat dams with warm preference subjected to herbal treatment that can improve kidney . The human relevance was confirmed by reduced serum corticosterone levels, and increased preference for warm location. RESULTS: KYD Rats were underdeveloped. Adenosine-triphosphate (ATP) production was reduced in the brown fat, but increased in the muscle. However, oxidative phosphorylated complexes to generate ATP and mitochondrial biogenesis marker were reduced in both tissues. When the second insult of high-fat diet (HFD) was introduced, KYD rats gained less weight yet developed more severe lipid and glucose metabolic disorders. This may be driven by disregulated liver gluconeogenesis marker forkhead box protein O1 and lipid metabolic regulator cholesterol 7 alpha-hydroxylase. CONCLUSION: KYD rats exhibited reduced mito-chondrial function in the brown fat, but were partially compensated by skeletal muscle, associated with the phenotype of warm preference and metabolic disorder, which was further exacerbated by additional HFD consumption. Future studies can focus on treatment targetting mitochondria function to reverse this phenotype.

Combinations of Tibetan tea and medicine food homology herbs: A new strategy for obesity prevention.

Obesity has become a significant global public health problem. Functional drinks have been an essential direction for obesity prevention research. The present study investigated the preventive effect and safety of winter melon and lotus leaf Tibetan tea (WLTT, a compound tea drink based on Ya'an Tibetan Tea and medicine food homology herbs) on obesity. The rats' hypercaloric high-fat diet (HFD) obesity model was established to evaluate obesity prevention and explored the mechanism through intestinal flora regulation. The results showed that in obese rats with the intervention of WLTT (400, 800, and 1600 mg/kg BW), the body weight, fat accumulation, adipocyte cell size, serum lipid levels, and antioxidant enzyme activity (SOD, GSH-Px, and MDA) were progressively improved. 16S rRNA high-throughput sequencing showed that WLTT could improve intestinal flora disorders due to HFD, which significantly reversed the relative abundance of Firmicutes and the F/B ratio associated with an HFD, and significantly upregulated the relative abundance of Verrucomicrobia. At the genus level, the downregulation of the relative abundance of Akkermansia and unclassified_Lachnospiraceae groups, and the upregulation of the relative abundance of Romboutsia, Ruminococcus, Corynebacteriume, and Saccharibacteria_genera_incertae_sedis groups brought about by the HFD were significantly reversed. The results of the above experiments were compared favorably with those of a parallel experiment with Bi -Sheng -Yuan slimming tea (BSY, a functional drink based on green tea and medicine food homology herbs). Overall, the findings have provided that WLTT can prevent obesity owing to an HFD by regulating intestinal flora and has a good safety profile, and combinations of Tibetan tea and medicine food homology herbs could be a new option for obesity prevention.

Characterization and quantification of the Chinese medical formula Zhi-Zi-Chi decoction, a systematic strategy for the attenuation and synergy of compatibility mechanism.

Zhi-Zi-Chi decoction (ZZCD), comprising of Gardenia jasminoides Ellis (GJE) and Semen sojae preparatum (SSP), is a classical Chinese medicine formula. A novel analysis strategy was set up to obtain an evaluation of ZZCD on attenuation and synergy of compatibility. High-resolution ion trap/time-of-flight mass spectrometry (LC-IT-TOF-MS) was used for qualitative analysis. Variant ingredients were analyzed to compare the componential differences between ZZCD formula and single herbs. Based on our previous fingerprint studies that combined with chemometric methods, 13 remarkable chemical markers were selected and evaluated for quantitative determination by high performance liquid chromatography (HPLC) in three different ratios of ZZCD. 62 compounds in ZZCD, 55 compounds in GJE and 16 compounds in SSP were characterized. The compatibility of GJE and SSP may lead to the undetection of hepatotoxic components such as genipin and the emergence of protective components such as jasminoside A, which was not found in single herbs. Meanwhile, 13 selected chemical markers were successfully determined in three ratios of ZZCD. The compatibility may lead to the decrease of toxic ingredients and the increase of beneficial ingredients. By comparing the dissolution of chemical markers, iridoids in GJE and flavonoids in SSP had the best dissolution when the compatibility ratio was 1:1. This strategy would be a valuable reference for further study on the compatibility of traditional Chinese medicine formula.

Phosphorus use efficiency has crossed the turning point of the environmental kuznets curve: Opportunities and challenges for crop production in China.

The overuse of phosphate fertilizer causes waste of resources and is detrimental to the sustainability of agriculture and aquatic systems. Effective management of phosphorus (P) in agricultural systems is important. Lack of understanding on the temporal and spatial variations of P utilization in farmland systems would constrain the development of more precise and effective policies as well as management practices. Here, we used two indicators, P use efficiency (PUE) and P surplus (Psur), to evaluate changes in P utilization in crop production on both national and regional scale in China during 2005-2018. Great heterogeneity of PUE and Psur were found across different regions, with Northeast of China showing the highest PUE (0.67) and lowest Psur (11.0 kg/ha). For temporal trends, our study showed that China crossed the turning point of the environmental Kuznets curve in 2007, which indicates that China has reached a new development stage of P use that is resource-saving and environmentally friendly. Along with the processes of industrialization and urbanization in China, the development of agricultural mechanization has further resulted in an increase of PUE and decrease of Psur. Although great efforts were made, China still has a relative low PUE and high Psur compared to developed countries. Our results suggest a regionalized perspective for developing policies for the sustainable use of P resources.

Effect of temperature variation on phosphorus flux at the sediment-water interface of the steppe wetlands.

Environmental factors are generally considered to be important factors affecting the release process of phosphorus (P) in sediments. However, little is known about the effect of temperature increased at first and then decreased with the season change on the P flux rate and flux amount at the sediment-water interface in the steppe wetlands. The effects of the temperature variation on P flux at the sediment-water interface in the steppe wetlands during the vegetation growing season under simulated wetland habitat were studied. The results showed that the release of P from sediments to overlying water was greatly affected by temperature changes. When the temperature rose, P was released from the sediment into the overlying water, while P was precipitated from the water into the sediment with the temperature dropped. During simulation period, the total P in water flux rates between sediment and overlying water (FP) was ranged from - 4.51 to 4.99 mg·m-2·day-1, while the dissolved reactive P in water flux rates between sediment and overlying water (FDP) was changed from - 5.37 to 5.14 mg·m-2·day-1. The FP and FDP were negatively correlated with the content of total P in water (WTP), dissolved reactive P in water (WDRP), pH of sediment (pH), and microbial biomass P (MBP), but increased with temperature (T), aluminum phosphate (Al.P), and occluded phosphate (Oc.P). The P flux rates were affected by temperature variation both directly and indirectly; the mechanism of how temperature influenced the fate of P in the wetland is still not clear. Therefore, the physicochemical properties and kinetic, thermodynamic, and microbiology characteristics should be combined together to clarify the mechanism in future research.

Modulation of cerebral cortex activity by acupuncture in patients with prolonged disorder of consciousness: An fNIRS study.

Background and objective: Acupuncture is a promising non-pharmacological therapy for patients with prolonged disorder of consciousness (PDOC); however, its underlying mechanism remains uncertain. This study aimed to reveal the modulatory effects of acupuncture on the cerebral cortex activity among patients with PDOC. Materials and methods: Twenty-eight PDOC patients were randomly assigned to the treatment (n = 14) or control (n = 14) group. The treatment group received one session of acupuncture, while the control group received one session of sham acupuncture. All patients underwent evaluation of the functional connectivity and activation response of the dorsolateral prefrontal cortex (DLPFC), primary motor cortex (M1), and primary somatosensory cortex (S1) via functional near-infrared spectroscopy. We further explored the potential correlation of the consciousness level and activation response/functional connectivity with acupuncture. Results: Compared to the control group, a single session of acupuncture significantly tended to enhance resting-state functional connectivity (rsFC) in DLPFC-M1, DLPFC-M1, and S1-S1. And the activation level of the DLPFC (both sides) in the acupuncture group is significantly higher than those in sham acupuncture group. However, no significant correlation was found between the consciousness level and activation response/functional connectivity. Conclusion: One session of acupuncture has a significant modulation of rsFC and activation in the DLPFC, M1, and S1 with PDOC patients. Acupuncture-evoked effect may have some functional significance in PDOC patients. This is an important step toward exploring the acupuncture effects on PDOC patients.

Study on the mechanism of Jin Gui Shen Qi Pill in the treatment of erectile dysfunction based on bioinformatics analysis.

Erectile dysfunction (ED) is a male disease, which is easy to cause disharmony in sexual life. However, at present, there are few drugs with small side effects in clinic. Jin Gui Shen Qi Pill (JGSQP) is a traditional Chinese medicine compound with obvious clinical effect in treating ED. Therefore, it is imperative to explore clinical drugs based on inhibiting the pathological characteristics of ED. First, the active ingredients and action targets in JGSQP were screened by applying Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SWISS Target Prediction. Further, a systematic pharmacological analysis platform for traditional Chinese medicine, and the ED targets were screened by applying Gene Cards and Online Mendelian Inheritance in Man databases to construct drug active ingredient-target-disease mapping, followed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction (PPI) network analysis. Finally, Molecular docking and molecular dynamics simulations were used to screen the active ingredients of JGSQP acting on PDE-5, and analyze the ligand-receptor interaction relationship and binding free energy. The results showed that there were 212 potential targets of JGSQP for ED disease, and GO analysis revealed that the main pathways were positive regulation of DNA-binding transcription factor activity, regulation of vascular diameter, and negative regulation of vascular diameter, etc. KEGG analysis revealed that the main pathways were HIF-1 signaling pathway, prolactin signaling pathway, fluid shear stress, and atherosclerosis, etc. PPI network analysis revealed that the core targets TGFB1 and EGFR have important roles. Molecular docking and molecular dynamics simulations showed that the main components acting on PDE-5 were MOL000546, MOL011169, MOL000279, MOL000273 and Sildenafil. MOL000546 was able to bind stably to PDE-5. The multi-component, multi-target, and multi-pathway action characteristics of JGSQP were confirmed by network pharmacology, which predicted the possible mechanism of action of JGSQP in the treatment of ED and provided a theoretical reference for further experimental validation.

Oral health-related multiple outcomes of holistic health in elderly individuals: An umbrella review of systematic reviews and meta-analyses.

Background and aims: Along with an aging population, exploring the impact of oral health on holistic health and determining exact outcomes in elderly individuals are important in both scientific research and clinical practice. Significant increase in the number of systematic reviews shows that oral health can directly or indirectly affect the overall health of elderly people physically, mentally and socially. To systematically collate, appraise, and synthesize the current evidence, we carried out an umbrella review of the impacts of oral health on holistic health in elderly individuals. Methods: A systematic reviews and meta-analyses search was performed in the major databases PubMed, MEDLINE, Web of Science and the Cochrane Library from inception to February 1, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The JBI (Joanna Briggs Institute) Critical Appraisal Checklist for Systematic Reviews and Research Syntheses was referred to assess methodological quality, and the GRADE (Grading of Recommendations, assessment, Development, and Evaluation working group classification) was used to assess the quality of evidence for each outcome included in the umbrella review. Results: Out of 1,067 records, a total of 35 systematic reviews were included. Respiratory diseases, malnutrition, age-related oral changes, frailty, cognitive impairment, depression and poor quality of life were identified as seven key outcomes that affect the physical, mental and social health of elderly individuals. Meanwhile, three intervention measures of oral health were summarized as (i) more rigorous and universal scales, (ii) dental cleaning and denture installation, and (iii) improving self-awareness regarding oral care. Conclusions: Evidence showed that oral health can significantly affect holistic health, and the diverse oral diseases directly lead to multiple health outcomes in elderly individuals. Clear high-quality evidence revealed that oral health is strongly associated with seven health outcomes covering physical, mental, and social levels, which directly corresponds to holistic health, and impacts the quality of life of elderly individuals. Such the results remind the importance of oral care in public health, and further studies need to be conducted to verity more specific association between oral health and other chronic diseases. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42022315315.

Systematic Identification, Fragmentation Pattern, And Metabolic Pathways of Hyperoside in Rat Plasma, Urine, And Feces by UPLC-Q-Exactive Orbitrap MS.

Hyperoside is a natural flavonol glycoside, which has antioxidation, antitumor, and anticancer activities together with other healthy effects like improving cardiovascular function, protecting the liver, and regulating the immune system. It is a popular compound used in the traditional Chinese medicine and different studies on hyperoside are present in the literature. However, studies on the metabolism of hyperoside in vivo were not comprehensive. In this study, UPLC-Q-Exactive Orbitrap MS technology was used to establish a rapid and comprehensive analysis strategy to explore the metabolites and metabolic process of hyperoside in rats. The metabolites of hyperoside were systematically identified in rat plasma, urine, and feces. According to the hyperoside standard substance and relevant works of literature, a total of 33 metabolites were identified, including 16 in plasma, 31 in urine, and 14 in feces. Among them, the metabolites quercetin and dihydroquercetin were unambiguously confirmed by comparison with standard substances. In addition, 13 metabolites had not been reported in hyperoside metabolism-related articles at present. The metabolic reactions of hyperoside in vivo were further explored, including phase I metabolism (hydroxylation, dehydroxylation, glycoside hydrolysis, hydrogenation, and hydration) and phase II metabolism (methylation, acetylation, sulfation, and glucuronide conjugation). The fragment ions of hyperoside and its metabolites were usually produced by glucoside bond hydrolysis, the neutral loss of (CO + OH), COH, CO, O, and Retro-Diels Alder (RDA) cleavage. In conclusion, this study comprehensively characterized the metabolism of hyperoside in rats, providing a basis for exploring its various biological activities.