Comparative efficacy of antifungal drugs for the treatment of oral candidiasis in HIV-positive patients: A Bayesian network meta-analysis.

Oral candidiasis infection is particularly prevalent among individuals in HIV-positive patients. Antifungal drugs have shown promising therapeutic effects in treating oral candidiasis in HIV-positive patients. However, the selection of specific antifungal drugs for the treatment of oral candidiasis in HIV-positive patients lacks evidence-based guidelines. This study aims to address this gap by conducting a comprehensive review of relevant randomized controlled trials (RCTs) and performing a network meta-analysis to assess the efficacy of different antifungal drugs in treating oral candidiasis in HIV-positive patients. A systematic search was conducted in databases including EMBASE, Web of Science, Medline, and Cochrane databases to identify relevant articles. Additionally, key pertinent sources in the literatures were also reviewed. All studies published prior to August 2023 were eligible for inclusion. Two researchers independently conducted the screening of literature, extraction of data, and evaluation of quality. Pairwise and network meta-analysis were then performed to assess the primary outcomes of the randomized controlled trials (RCTs) included. The protocol was registered on the PROSPERO database (CRD42024513912). Twenty-six RCTs were included in this meta-analysis, involving a total of 3145 patients and evaluating seven interventions (placebo, fluconazole, itraconazole, nystatin, clotrimazole, ketoconazole, miconazole). Pairwise meta-analysis and network meta-analysis showed fluconazole was significantly efficacy in increasing mycological cure rates when compared with placebo, clotrimazole, and nystatin. Ketoconazole and miconazole were significantly efficacy in increasing mycological cure rates when compared with nystatin. Network meta-analysis also suggested the efficacy of the seven interventions in increasing mycological cure rates was ranked as follows: placebo (35.3%), fluconazole (95.2%), itraconazole (61.6%), nystatin (17.0%), clotrimazole (52.7%), ketoconazole (69.2%), miconazole (69.1%). The available evidence indicates that fluconazole had the greatest possibility to increase mycological cure rates in HIV-positive patients, while, nystatin was the least effective antifungal drug in increasing mycological cure rates in HIV-positive patients.

Long-term Bisphenol S exposure induced gut microbiota dysbiosis, obesity, hepatic lipid accumulation, intestinal lesions and dyslipidemia in mice.

Bisphenol S (BPS) is a commonly detected chemical raw material in water, which poses significant threats to both the ecological environment and human health. Despite being recognized as a typical endocrine disruptor and a substitute for Bisphenol A, the toxicological effects of BPS remain nonnegligible. In order to comprehensively understand the health impacts of BPS, a long-term (154 days) exposure experiment was conducted on mice, during which the physiological indicators of the liver, intestine, and blood were observed. The findings revealed that exposure to BPS resulted in dysbiosis of the gut microbiota, obesity, hepatic lipid accumulation, intestinal lesions, and dyslipidemia. Furthermore, there exists a significant correlation between gut microbiota and indicators of host health. Consequently, the identification of specific gut microbiota can be considered as potential biomarkers for the evaluation of risk associated with BPS. This study will effectively address the deficiency in toxicological data pertaining to BPS. The novel BPS data obtained from this research can serve as a valuable reference for professionals in the field.

Six polyoxotungstate-based transition metal compounds for electrochemical capacitor application and a comparative analysis of factors affecting capacitances.

Six different polyoxotungstate-based transition metal complexes were synthesized, namely [Cu5(2,2'-bpy)5(µ2-Cl)2(PO4)2(H2O)2][HPW12O40]·2H2O (1), [Cu1.5(2,2'-bpy)1.5(inic)2(H2O)1.5]3[H1.5PW12O40]2·16.25H2O (2), [Cu(2,2'-bpy)2]2[SiW12O40]·10H2O (3), [Zn(phen)3]2[PWVWVI11O40]·5H2O (4), [Zn(phen)2(H2O)]2[SiW12O40]·2H2O (5), and [Zn(2,2'-bpy)2]2[SiW12O40] (6) (2,2'-bpy = 2,2'-bipyridine, inic = isonicotinic acid, phen = 1,10-phenanthroline). Compound 1 is based on [HPW12O40]2- anions, which are accommodated within the open channels of a supramolecular network formed by novel Cu-P-Cl coordination clusters. Compound 2 is constructed from [H1.5PW12O40]1.5- and novel [Cu1.5(2,2'-bpy)1.5(inic)2(H2O)1.5]+ coordination fragments, and polyoxoanions are encapsulated within the pores created by the copper coordination fragments, resulting in a unique three-dimensional supramolecular architecture. Compound 3 is a two-dimensional structure formed through the covalent linkage between [SiW12O40]4- and [Cu(2,2'-bpy)2]2+. Compound 4 is a supramolecular architecture formed by [PWVWVI11O40]4- and [Zn(phen)3]2+ coordination fragments, while compound 5 is a supramolecular structure based on POM bi-supported Zn coordination complexes. Compound 6 is a two-dimensional framework structure constituted by [SiW12O40]4- and [Zn(2,2'-bpy)2]2+via covalent interactions. In addition, electrochemical measurement results show that the copper-based tungstate compounds 1-3 and zinc-based tungstate compounds 4-6 exhibit different performances and durabilities as electrochemical capacitors (compound 1 shows the highest specific capacitance of 94.0 F g-1 at 1.5 A g-1, whereas compound 6 maintains the best cycling stability with the capacity retention of 80.7% after 1000 cycles at 4 A g-1.). This study contributes to the development of POM-based transition metal complexes with high capacitance by providing insights into the design and synthesis process.

Magnetic resonance imaging on brain structure and function changes in diabetic peripheral neuropathy.

With the significant increase in the global prevalence of diabetes mellitus (DM), the occurrence of diabetic peripheral neuropathy (DPN) has become increasingly common complication associated with DM. It is particularly in the peripheral nerves of the hands, legs, and feet. DPN can lead to various adverse consequences that greatly affect the quality of life for individuals with DM. Despite the profound impact of DPN, the specific mechanisms underlying its development and progression are still not well understood. Advancements in magnetic resonance imaging (MRI) technology have provided valuable tools for investigating the central mechanisms involved in DPN. Structural and functional MRI techniques have emerged as important methods for studying the brain structures and functions associated with DPN. Voxel-based morphometry allows researchers to assess changes in the volume and density of different brain regions, providing insights into potential structural alterations related to DPN. Functional MRI investigates brain activity patterns, helping elucidate the neural networks engaged during sensory processing and pain perception in DPN patients. Lastly, magnetic resonance spectroscopy provides information about the neurochemical composition of specific brain regions, shedding light on potential metabolic changes associated with DPN. By synthesizing available literature employing these MRI techniques, this study aims to enhance our understanding of the neural mechanisms underlying DPN and contribute to the improvement of clinical diagnosis.

Comparison of dexmedetomidine and dexamethasone as adjuvants to the ultrasound-guided interscalene nerve block in arthroscopic shoulder surgery: a systematic review and Bayesian network meta-analysis of randomized controlled trials.

Introduction: Interscalene block (ISB) is widely regarded as the gold standard treatment for acute pain following arthroscopic shoulder surgery. However, a single injection of a local anesthetic for ISB may not offer sufficient analgesia. Various adjuvants have been demonstrated to prolong the analgesic duration of the block. Hence, this study aimed to assess the relative efficacy of dexamethasone and dexmedetomidine as adjuncts to prolong the analgesic duration for a single- shot ISB. Methods: The efficacy of adjuvants was compared using a network meta-analysis. The methodological quality of the included studies was evaluated using the Cochrane bias risk assessment tool. A comprehensive search of the PubMed, Cochrane, Web of Science, and Embase databases was conducted with a search deadline of March 1, 2023. Various adjuvant prevention randomized controlled trials have been conducted in patients undergoing interscalene brachial plexus block for shoulder arthroscopic surgery. Results: Twenty-five studies enrolling a total of 2,194 patients reported duration of analgesia. Combined dexmedetomidine and dexamethasone (MD = 22.13, 95% CI 16.67, 27.58), dexamethasone administered perineurally (MD = 9.94, 95% CI 7.71, 12.17), high-dose intravenous dexamethasone (MD = 7.47, 95% CI 4.41, 10.53), dexmedetomidine administered perineurally (MD = 6.82, 95% CI 3.43, 10.20), and low-dose intravenous dexamethasone (MD = 6.72, 95% CI 3.74, 9.70) provided significantly longer analgesic effects compared with the control group. Discussion: The combination of intravenous dexamethasone and dexmedetomidine provided the greatest effect in terms of prolonged analgesia, reduced opioid doses, and lower pain scores. Furthermore, peripheral dexamethasone in prolonging the analgesic duration and lowering opioid usage was better than the other adjuvants when used a single medication. All therapies significantly prolonged the analgesic duration and reduced the opioid dose of a single-shot ISB in shoulder arthroscopy compared with the placebo.

Structural and functional activities of brain in patients with vascular cognitive impairment: A case-controlled magnetic resonance imaging study.

This study aimed to identify abnormal brain regions and imaging indices of vascular cognitive impairment (VCI) and explore specific imaging diagnostic markers of VCI. In this study, 24 patients with VCI were allocated to the VCI group and 25 healthy subjects were assigned to the healthy control (HC) group. Demographic data and neuropsychological test scores were compared using SPSS 25.0. The structural and functional imaging data were post-processed and statistically analyzed using CAT12, DPARSF and SPM12 software, based on the MATLAB platform. The structural and functional indices of gray matter volume (GMV) and regional homogeneity (ReHo) were obtained, and inter-group data were analyzed using an independent-sample t test. Sex, age, years of education, and total brain volume were used as covariates. Compared to the HC group, the GMV of VCI in the VCI group decreased significantly in the rectus muscles of the bilateral gyrus, left superior temporal gyrus, left supplementary motor area (SMA), right insula, right superior temporal gyrus, right anterior cuneiform lobe, and right anterior central gyrus (PRECG) (P < .05, FWE correction), without GMV enlargement in the brain area. ReHo decreased in the right inferior temporal gyrus (ITG), right parahippocampal gyrus, and left temporal pole (middle temporal gyrus, right lingual gyrus, left posterior central gyrus, and right middle temporal gyrus), the areas of increased ReHo were the left caudate nucleus, left rectus gyrus, right anterior cingulate gyrus and lateral cingulate gyrus (P < .05, FWE correction). Correlation analysis showed that the GMV of the left superior temporal gyrus was positively correlated with the Montreal Cognitive Assessment (MoCA) score (P < .05), and the GMV of the right insula was positively correlated with the MESE and long delayed memory scores (P < .05). There was a significant positive correlation between the ReHo and short-term delayed memory scores in the middle temporal gyrus of the left temporal pole (P < .05). The volume of GMV and ReHo decreased in VCI patients, suggesting that impairment of brain structure and function in specific regions is the central mechanism of cognitive impairment in these patients. Meanwhile, the functional indices of some brain regions were increased, which may be a compensatory mechanism for the cognitive impairment associated with VCI.

Bisphenol F induced hyperglycemia via activation of oxidative stress-responsive miR-200 family in the pancreas.

Bisphenol F (BPF), BPS and BPAF are gaining popularity as main substitutes to BPA, but there is no clear evidence that these compounds disrupt glycemic homeostasis in the same way. In this study, four bisphenols were administered to C57BL/6 J mice, and showed that the serum insulin was elevated in the BPA and BPS exposed mice, whereas BPF exposed mice exhibited lower serum insulin and higher blood glucose. BPF decreased oxidized glutathione/reduced glutathione ratio (GSSG/GSH) and N6-methyladenosine (m6A) levels, which was responsible for pancreatic apoptosis in mice. Additionally, the downregulation of Nrf2 and the aberrant regulation of the p53-lncRNA H19 signaling pathway further increased miR-200 family in the BPF-exposed pancreas. The miR-200 family directly suppressed Mettl14 and Xiap by targeting their 3' UTR, leading to islet apoptosis. Antioxidant treatment not only elevated m6A levels and insulin contents but also suppressed the miR-200 family in the pancreas, ultimately improving BPF-induced hyperglycemia. Taken together, miR-200 family could serve as a potential oxidative stress-responsive regulator in the pancreas. And moreover, we demonstrated a novel toxicological mechanism in that BPF disrupted the Keap1-Nrf2 redox system to upregulate miR-141/200b/c which controlled pancreatic insulin production and apoptosis via Mettl14 and Xiap, respectively. As the major surrogates of BPA in various applications, BPF was also diabetogenic, which warrants attention in future research.

Three new constituents from the Tujia ethnomedicine Swertia punicea Hemsl.

Three new constituents: 1,5R-dihydroxy-3,8S-dimethoxy-5,6,7,8-tetrahydroxanthone (1), (3S,4R,16S,17R)-3,16,23-trihydroxyoleana-11,13(18)-dien-28-aldehyde-3-O-ß-D-glucopyranoside (2), and new natural product (S)-gentiandiol (3), along with 41 known compounds were isolated from Tujia ethnomedicine Shuihuanglian, namely, the whole plant of Swertia punicea. Structures of all these compounds were established through extensive spectroscopic techniques, namely 1D, 2D-NMR spectroscopy, HRESIMS analysis, and the absolute configuration of the new compounds was discerned by circular dichroism (CD) spectroscopy. Antioxidative effects of these compounds were evaluated by using the DPPH radical scavenging method, compounds 7, 9 and 14 showed antioxidant activities with IC50 values of 68.9, 50.8 and 48.2 µM, respectively.

Efficacy of vitamin D supplementation on child and adolescent overweight/obesity: a systematic review and meta-analysis of randomized controlled trials.

The global prevalence of overweight and obesity in children and adolescents has been increasing. Child and adolescent overweight/obesity has been demonstrated to be partially associated with vitamin D deficiency. This systematic review and meta-analysis aims to assess the efficacy of vitamin D supplementation on child and adolescent overweight/obesity. PubMed, Embase, Cochrane Library, and Web of science were searched from inception to June 20th, 2022. Randomized controlled trials (RCTs) assessing the efficacy of vitamin D on child and adolescent overweight/obesity were included. The Cochrane bias risk assessment tool was used to assess the bias risk of included studies, and subgroup analysis was conducted based on different administration dosages. All data-analyses were performed using R 4.2.1. There were 1502 articles retrieved, and 10 eligible studies were finally included, with a total of 595 participants. Meta-analysis showed no differences in LDL, TC, TG, BMI, ALP, Ca, and PTH between vitamin-D (Vit-D) group and placebo, while Vit-D group resulted in improved HOMA-IR[WMD = - 0.348, 95%CI (- 0.477, - 0.219), p = 0.26]. Subgroup-analysis showed no significant difference in the increase of 25-(OH)-D between subgroups (p = 0.39), whereas the serum 25-(OH)-D level was increased under different Vit-D doses [WMD = 6.973, 95%CI (3.072, 10.873)]. High daily dose (≥ 4000 IU/d) of Vit-D might decrease CRP and increase HDL levels.   Conclusion: High dose of Vit-D supplementation (over 4000 IU/d) would reduce several cardiometabolic risk indicators and improve insulin resistance. More high-quality and large-scale RCTs are needed to provide more robust evidence. What is Known: • Vit-D deficiency is common in overweight/obesity (OW/OB) children and adolescents. • Previous randomized studies on the benefit of Vit-D supplementation to OW/OB children and adolescents are inconsistent. What is New: • This is the first meta-analysis conducted to assess the efficacy of Vit-D supplementation on child and adolescent OW/OB. • High dose of Vit-D supplementation is beneficial to cardiovascular metabolism, and improve insulin resistance on child and adolescent OW/OB.

Two new dammarane triterpenoid saponins from the leaves of Cyclocarya paliurus.

Two undescribed dammarane triterpenoid saponins, cypaliurusides O and P (1 and 2), were isolated from the ethanol extracts of the leaves of Cyclocarya paliurus. Bioactivity assay results showed that compound 1 has potential cytotoxic activities against selected human cancer cell lines in vitro, with IC50 values ranging from 14.55 ± 0.55 to 22.75 ± 1.54 µM. Compound 1 showed better antitumor activity against HepG2 cells with IC50 of 14.55 ± 0.55 µM. In addition, compound 2 showed no obvious antitumor activity.

Efficacy and adverse effects of peripheral nerve blocks and local infiltration anesthesia after arthroscopic shoulder surgery: A Bayesian network meta-analysis.

Study objective: To quantitatively assess and compare the efficacy and adverse effects of six different peripheral nerve block techniques after arthroscopic shoulder surgery (ASS). Design: Bayesian network meta-analysis. Methods: The PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure database, Chinese Scientific Journal database, Wan Fang databases were searched to retrieve randomized clinical trials comparing interscalene brachial plexus block, continuous interscalene brachial plexus block, supraclavicular brachial plexus block, suprascapular nerve block, combined suprascapular and axillary nerve block and local infiltration analgesia on postoperative pain, opioid consumption, and adverse effects (defined as Horner's syndrome, dyspnea, hoarseness, vomiting, and nausea) after ASS under general anesthesia (GA). Two reviewers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Results: A total of 1,348 articles were retrieved initially and 36 randomized clinical trials involving 3,124 patients were included in the final analysis. The network meta-analysis showed that interscalene brachial plexus block was superior in reducing pain and opioid consumption compared to the five other interventions. However, adverse effects were reduced using suprascapular nerve block and combined suprascapular and axillary nerve block compared to interscalene brachial plexus block. Conclusion: Interscalene brachial plexus block was superior in reducing pain and opioid consumption compared to other peripheral nerve blocks but had a higher frequency of adverse events.

Heilaohuacid G, a new triterpenoid from Kadsura coccinea inhibits proliferation, induces apoptosis, and ameliorates inflammation in RA-FLS and RAW 264.7 cells via suppressing NF-𝜠B pathway.

Heilaohu, the roots of Kadsura coccinea, has been used in Tujia ethnomedicine to treat rheumatic arthritis (RA). Heilaohuacid G (1), a new 3,4-seco-lanostane type triterpenoid isolated from the ethanol extract of Heilaohu, whose structure was determined using HR-ESI-MS data, NMR spectroscopic analyses, and ECD calculations. In this study, our purpose is to elucidate the mechanisms of Heilaohuacid G in the treatment of RA by inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells and inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. The biological activity screening experiments indicated that Heilaohuacid G significantly inhibited proliferation of RA-FLS cells with IC50 value of 8.16 ± 0.47 µM. CCK-8 assay, ELISA, flow cytometry assay, and Western blot were used to measure the changes of cell viability, apoptosis, and the release of inflammatory cytokines. Heilaohuacid G was found not only induced RA-FLS cell apoptosis, but also inhibited the inflammatory reactions in LPS-induced RA-FLS and RAW 264.7 cell lines via inhibiting NF-κB pathway. Furthermore, Heilaohuacid G (p.o.) at doses of 3.0, 6.0, and 12.0 mg/kg and the ethanol extracts of Heilaohu (p.o.) at doses of 200, 400, and 800 mg/kg both were confirmed antiinflammatory effects on xylene-induced ear mice edema model.

Anti-inflammatory and antioxidant activities of chemical constituents from the flower buds of Buddleja officinalis.

Five new glycosides including mimenghuasu A and B (1-2), isolinarin (3), cyclocitralosides A and B (4-5), along with forty-seven known compounds were isolated from the flower buds of Buddleja officinalis. These structures were elucidated by extensive spectroscopic analysis (UV, IR, 1 D, 2 D NMR, and MS spectra). The anti-inflammatory activities of the isolated compounds were determined by enzyme-linked immunosorbent assay (ELISA) on the expression of TNF-α (LPS-activated RAW264.7 cells) and MTT experiment on LPS-induced HUVECs proliferation effects. Good suppressive effects on the expression of TNF-α were shown by 4 and 5 with IC50 values of 19.35 and 22.10 µM, respectively, compared to positive control indomethacin (IC50 16.40 µM). In addition to this, some isolated compounds exhibited excellent antioxidant activities including compounds 16, 18, 29, 39, and 47 (IC50 µM: 82.59, 72.94, 33.65, 46.67, and 20.81, respectively) with almost the same or stronger potency with reference to vitamin C as positive control (IC50 81.83 µM).

Triterpenoids From Kadsura coccinea With Their Anti-inflammatory and Inhibited Proliferation of Rheumatoid Arthritis-Fibroblastoid Synovial Cells Activities.

One new 3,4-seco-17,13-friedo-lanostane triterpenoid heilaohuacid A (1), one new 3,4-seco-17,14-friedo-lanostane triterpenoid heilaohuacid B (2), five new 3,4-seco-lanostane triterpenoids heilaohuacids C-D (3-4) and heilaohumethylesters A-C (7-9), one new 3,4-seco-cycloartane triterpenoid heilaohuacid E (5), and one new intact-lanostane triterpenoid heilaohuacid F (6), together with twenty-two known analogues (10-31), were isolated from heilaohu. Their structures were determined using HR-ESI-MS data, 1D and 2D NMR spectra, 13C NMR calculations, and electronic circular dichroism (ECD) calculations. Heilaohuacids A and B (1 and 2) contain a 3,4-seco ring A and unprecedented migration of Me-18 from C-13 to C-17 or C-14 to C-18. This type of lanostane triterpenoid derivatives was rarely reported so far. More importantly, all compounds against inflammatory cytokines IL-6 and TNF-α levels on LPS-induced RAW 264.7 macrophages were evaluated, and compounds 4 and 31 significantly inhibited the release level of IL-6 with IC50 values of 8.15 and 9.86 µM, respectively. Meanwhile, compounds 17, 18, and 31 significantly inhibited proliferation of rheumatoid arthritis-fibroblastoid synovial (RA-FLS) cells in vitro with IC50 values of 7.52, 8.85, and 7.97 µM, respectively.

Heilaohuguosus A-S from the fruits of Kadsura coccinea and their hepatoprotective activity.

Phytochemical investigations on the fresh fruits of Kadsura coccinea (Lem.) A. C. Sm. have led to the isolation of fourteen undescribed 2,2'-cyclolignans named heilaohuguosus A-N, four undescribed aryltetrahydronaphthalene lignans, heilaohuguosus O-R and one tetrahydrofuran lignan, heilaohuguosu S, with twenty-seven previously described lignan analogues. Their structures and absolute configurations of heilaohuguosus A-S were established by spectroscopic methods including 1D and 2D-NMR techniques and CD experiments. All isolated compounds were evaluated for their hepatoprotective activity against APAP-induced toxicity in HepG-2 cells, four 2,2'-cyclolignans, heilaohuguosus A and L, tiegusanin I and kadsuphilol I showed good hepatoprotective activities against APAP toxicity in HepG-2 cells with cell survival rates of 53.5 ± 1.7%, 55.2 ± 1.2%, 52.5 ± 2.4%, and 54.0 ± 2.2% (positive control bicyclol, 52.1 ± 1.3%) at 10 µM, respectively.

Metformin relieves H/R-induced cardiomyocyte injury through miR-19a/ACSL axis - possible therapeutic target for myocardial I/R injury.

This study proposed to investigate the function of miR-19a/ACSL axis in hypoxia/reoxygenation (H/R)-induced myocardial injury and determine whether metformin exerts its protective effect via miR-19a/ACSL axis. Firstly, bioinformatics analysis of data from Gene Expression Omnibus (GEO) database indicated that miR-19a was downregulated in patients with myocardial infarction (MI) compared to that in control group. H/R model was constructed with AC16 cells in vitro. qRT-PCR assay revealed that miR-19a was downregulated in H/R-treated AC16 cells. Then, CCK-8 assay demonstrated that upregulation of miR-19a significantly alleviated H/R-induced decline of cell viability. Moreover, bioinformatics prediction, western blotting and dual-luciferase reporter assays were performed to check the target genes of miR-19a, and ACSL1 was determined as a downstream target gene of miR-19a. Besides, the analysis based on Comparative Toxicogenomics Database (CTD) suggested that metformin targeting ACSL1 can be used as a potential drug for further research. Biological function experiments in vitro revealed that H/R markedly declined the viability and elevated the apoptosis of AC16 cells, while metformin can significantly mitigate these effects. Furthermore, overexpression of miR-19a significantly strengthened the beneficial effect of metformin on H/R-induced AC16 cells injury, which can be reversed by upregulation of ACSL1. In conclusion, metformin can alleviate H/R-induced cells injury via regulating miR-19a/ACSL axis, which lays a foundation for identifying novel targets for myocardial I/R injury therapy.

A review of lignans from genus Kadsura and their spectrum characteristics.

Kadsura belongs to the Schisandroideae subfamily of Magnoliaceae. Plants from genus Kadsura are widely distributed in the South and Southwest of China. The plants of the genus are widely used as folk medicine for a long time in history, with the functions of relieving pain, promoting 'qi' circulation, activating blood resolve stasis, and applications in the treatment of rheumatoid arthritis and gastroenteric disorders. Lignans are the primary characteristic constituents with various biological activities of plants from genus Kadsura. This paper summarized 81 lignans isolated from the plants of genus Kadsura over the past eight years (from 2014 to 2021), which belong to five types: dibenzocyclooctadienes, spirobenzofuranoid dibenzocyclooctadienes, aryltetralins, diarylbutanes and tetrahydrofurans. Each type of these lignans possess typical characteristics in proton magnetic resonance (1H NMR) and carbon-13 nuclear magnetic resonance (13C NMR) spectra, the NMR regularities of these types of lingans were summarized, which provided a useful reference for the structural analysis of lignans. The relationships between lignans and pharmacodynamics were also systematically analyzed, lignans were predicted to be the quality markers (Q-marker) of Kadsura genus.

Kadsura heteroclita stem ethanol extract protects against carbon tetrachloride-induced liver injury in mice via suppression of oxidative stress, inflammation, and apoptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Kadsura heteroclita stem (KHS) is a well-known hepatoprotective Tujia ethnomedicine (folk named Xuetong), has long been used for the prevention and treatment of hepatitis and liver diseases. AIM OF THE STUDY: To explore the protective effects of KHS against carbon tetrachloride (CCl4)-induced liver injury and the underlying mechanism, particularly antioxidative, anti-inflammatory, and anti-apoptotic potentials. MATERIALS AND METHODS: The acute toxicity of KHS was measured by the method of maximum tolerated dose (MTD). Liver injury in mice was induced by intraperitoneal injection of 25% carbon tetrachloride (olive oil solubilization) 2 times every week. After modeling, mice in KHS groups were treated with KHS at 100, 200, 400 mg/kg/d, mice in positive control group were treated with bifendate (30 mg/kg/d), and mice in normal and model groups were given ultrapure water. After 4 weeks of treatment, blood of mice was taken from the orbital venous plexus before mice euthanized, the liver, spleen, and thymus of mice were weighed by dissecting the abdominal cavity after mice euthanized. Moreover, the liver of mice was selected for histological examination. The alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities in mice serum were measured using the automatic biochemical analyzer. The levels of superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione peroxidase (GPX-2), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), Bcl-2-associated X (Bax), B-cell lymphoma-2 (Bcl-2), Caspase-3, and Caspase-8 in mice liver were measured by Elisa kits. Furthermore, the protein expression of Bcl-2 and Bax in mice liver tissue was detected by Western blot. RESULTS: The MTD of KHS was determined to be 26 g/kg in both sexes of mice. Treatment with KHS dose-dependently protected the liver and other main organs against CCl4-induced liver injury in mice. The ALT and AST levels in mice liver were significantly reduced after treatment with KHS at the dose of 100, 200, and 400 mg/kg. In addition, the liver histopathological analyses revealed that KHS markedly alleviated inflammatory cell infiltration, hepatic fibrosis, hepatocyte ballooning, necrosis and severe apoptosis of hepatocytes induced by CCl4. Further assay indicated that KHS significantly suppressed the production of MDA and MPO, while markedly increased the level of SOD and GPx-2. The TNF-α and IL-6 level in mice liver tissue were decreased by KHS, whereas the IL-10 level was increased. KHS also inhibited hepatocyte apoptosis by significantly reducing the expression of Bax, Caspase-3, Caspase-8, as well as increasing the expression of Bcl-2. Besides, the Western blot results strongly demonstrated that KHS inhibited hepatocyte apoptosis, as evidenced by reducing the expression of Bax protein and increasing the expression of Bcl-2 protein in liver injury tissues. CONCLUSIONS: This research firstly clarified that KHS has a significant protective effect against CCl4-induced liver injury, which might be closely related to alleviating oxidative stress, reducing inflammatory response, and inhibiting hepatocyte apoptosis.

LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a fatal progressive disease characterized by an increased blood pressure in the pulmonary arteries. RhoA/Rho-kinase (RhoA/ROCK) signaling activation is often associated with PAH. The purpose of this study is to investigate the role and mechanisms of long noncoding RNA (lncRNA) smooth muscle-induced lncRNA (SMILR) to activate the RhoA/ROCK pathway in PAH. SMILR, microRNA-141 (miR-141), and RhoA were identified by qRT-PCR in PAH patients' serum. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), wound-healing assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were performed to determine cell viability, migration, proliferation, and cell cycle in human pulmonary arterial smooth muscle cells (hPASMCs) and primary PASMCs from PAH patients. We also performed bioinformatical prediction, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) to assess the interaction among SMILR, miR-141, and RhoA. The RhoA/ROCK pathway and proliferation-related proteins were measured by Western blotting. Finally, we introduced the small hairpin (sh)SMILR to monocrotaline-induced PAH rat model and used the hemodynamic measurement, qRT-PCR, and immunohistochemistry to examine the therapeutic effects of shSMILR. SMILR and RhoA expression were upregulated, while miR-141 expression was downregulated in PAH patients. SMILR directly interacted with miR-141 and negatively regulated its expression. Knockdown of SMILR suppressed PASMC proliferation and migration induced by hypoxia. Furthermore, overexpression of miR-141 could inhibit the RhoA/ROCK pathway by binding to RhoA, thereby repressing cell proliferation-related signals. Knockdown of SMILR significantly inhibited the Rho/ROCK activation and vascular remodeling in monocrotaline-induced rats. Knockdown of SMILR effectively elevated miR-141 expression and in turn inhibited the RhoA/ROCK pathway to regulate vascular remodeling and reduce blood pressure in PAH.NEW & NOTEWORTHY Smooth muscle enriched long noncoding RNA (SMILR), as a long noncoding RNA (lncRNA), was increased in pulmonary arterial hypertension (PAH) patients and in vitro and in vivo models. SMILR activated RhoA/ROCK signaling by targeting miR-141 to disinhibit its downstream target RhoA. SMILR knockdown or miR-141 overexpression inhibited hypoxia-induced cell proliferation and migration via repressing RhoA/ROCK signaling in pulmonary arterial smooth muscle cells (PASMCs), which was confirmed in vivo experiments that knockdown of SMILR inhibited vascular remodeling and alleviated PAH in rats. SMILR may be a promising and novel therapeutic target for the treatment and drug development of PAH.

Triterpenoids from stems of Kadsura heteroclita.

In the present work, we reported the triterpenoids isolated from n-butanol fraction of Kadsura heteroclita which is a Tujia ethnomedicine with trivial name "Xuetong". This effort resulted in the isolation of six unpresented triterpenoids xuetongsu A-F (1-6), along with five known triterpenoids (7-11). The structures of the reported compounds were established on the 1D, and 2D NMR and HRESIMS spectra, along with CD spectroscopic analysis. Moreover, the absolute stereochemistry of compound 7 was determined by X-ray diffraction analysis. Antioxidant and cytotoxic activities were evaluated for all isolated compounds, compound 7 shown weak cytotoxic activity against HL-60 with IC50 value of 50.0 µM.