Three new flavonoids from the roots of Sophora tonkinensis.

Three new flavonoids including two isoflavanones sophortones A and B (1 and 2), and one chalcone sophortone C (3) were isolated from the roots of Sophora tonkinensis. Their structures were established by UV, IR, HRESIMS, and NMR data. The absolute configurations of 1 and 2 were determined by electronic circular dichroism (ECD) calculations.

Tumor marker-based RecistTM is superior to RECIST as criteria to predict the long-term benefits of targeted therapy in advanced non-small-cell lung cancer with driver gene mutations.

BACKGROUND: Tyrosine kinase inhibitors (TKIs) are standard first-line treatments for advanced non-small-cell lung cancer (NSCLC) with driver gene mutations. The Response Evaluation Criteria in Solid Tumors (RECIST) are limited in predicting long-term patient benefits. A tumour marker-based evaluation criteria, RecistTM, was used to investigate the potential for assessing targeted-therapy efficacy in lung cancer treatment. METHODS: We retrospectively analysed patients with stage IIIA-IV NSCLC and driver gene mutations, whose baseline tumour marker levels exceeded the pre-treatment cut-off value three-fold and who received TKI-targeted therapy as a first-line treatment. We compared efficacy, progression-free survival (PFS), and overall survival (OS) between RecistTM and RECIST. FINDINGS: The median PFS and OS differed significantly among treatment-response subgroups based on RecistTM but not RECIST. The predicted 1-, 2-, and 3-year disease-progression risk, according to area under the receiver operating characteristic curve, as well as the 1-, 3-, and 5-year mortality risk, differed significantly between RecistTM and RECIST. The median PFS and OS of tmCR according to RecistTM, was significantly longer than (CR+PR) according to RECIST. Imaging analysis revealed that the ΔPFS was 11.27 and 6.17 months in the intervention and non-intervention groups, respectively, suggesting that earlier intervention could extend patients' PFS. INTERPRETATION: RecistTM can assess targeted-therapy efficacy in patients with advanced NSCLC and driver gene mutations, along with tumour marker abnormalities. RecistTM surpasses RECIST in predicting short- and long-term patient benefits, and allows the early identification of patients resistant to targeted drugs, enabling prompt intervention and extending the imaging-demonstrated time to progression.

Investigation of arsenic contamination in soil and plants along the river of Xinzhou abandoned gold mine in Qingyuan, China.

The exploitation of mineral resources is very important for economic development, but disorderly exploitation poses a serious threat to the ecological environment. However, investigations on the advantages of plant species and environmental pollution in polluted mining areas are limited. Thus, a survey was conducted to evaluate the impacts of abandoned mines on the surrounding ecological environment along rivers in polluted areas and to determine the Arsenic (As) pollution status in soil and plants. The results showed that the soil and vegetation along the river in the survey area were seriously polluted by As. The total As content of the 15 samples was significantly greater than the national soil background value (GB 15618-2018), and degree of pollution was nonlinearly related to the distance from the mine source, R2 = 0.9844. B. bipinnata, P. vittata and B. nivea were predominant with degrees of dominance of 0.01-0.33, 0.05-0.11, and 0.06-0.14 respectively. The As enrichment capacities of Juncus and P. vittata were significantly greater than those of the other plants, while the bioaccumulation factors (BCFs) were 21.81 and 7.04, respectively.

Effects of SARS-COV-2 infection during the frozen-thawed embryo transfer cycle on embryo implantation and pregnancy outcomes.

STUDY QUESTION: Does severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the frozen-thawed embryo transfer (FET) cycle affect embryo implantation and pregnancy rates? SUMMARY ANSWER: There is no evidence that SARS-CoV-2 infection of women during the FET cycle negatively affects embryo implantation and pregnancy rates. WHAT IS KNOWN ALREADY: Coronavirus disease 2019 (COVID-19), as a multi-systemic disease, poses a threat to reproductive health. However, the effects of SARS-CoV-2 infection on embryo implantation and pregnancy following fertility treatments, particularly FET, remain largely unknown. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study, included women who underwent FET cycles between 1 November 2022 and 31 December 2022 at an academic fertility centre. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who tested positive for SARS-CoV-2 during their FET cycles were included in the COVID-19 group, while those who tested negative during the same study period were included in the non-COVID-19 group. The primary outcome was ongoing pregnancy rate. Secondary outcomes included rates of implantation, biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy. Multivariate logistic regression models were applied to adjust for potential confounders including age, body mass index, gravidity, vaccination status, and endometrial preparation regimen. Subgroup analyses were conducted by time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) and by level of fever (no fever, fever <39°C, or fever ≥39°C). MAIN RESULTS AND THE ROLE OF CHANCE: A total of 243 and 305 women were included in the COVID-19 and non-COVID-19 group, respectively. The rates of biochemical pregnancy (58.8% vs 62.0%, P = 0.46), clinical pregnancy (53.1% vs 54.4%, P = 0.76), implantation (46.4% vs 46.2%, P = 0.95), early pregnancy loss (24.5% vs 26.5%, P = 0.68), and ongoing pregnancy (44.4% vs 45.6%, P = 0.79) were all comparable between groups with or without infection. Results of logistic regression models, both before and after adjustment, revealed no associations between SARS-CoV-2 infection and rates of biochemical pregnancy, clinical pregnancy, early pregnancy loss, or ongoing pregnancy. Moreover, neither the time of infection with respect to transfer (prior to transfer, 1-7 days after transfer, or 8-14 days after transfer) nor the level of fever (no fever, fever <39°C, or fever ≥39°C) was found to be related to pregnancy rates. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature of the study is subject to possible selection bias. Additionally, although the sample size was relatively large for the COVID-19 group, the sample sizes for certain subgroups were relatively small and lacked adequate power, so these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study findings suggest that SARS-CoV-2 infection during the FET cycle in females does not affect embryo implantation and pregnancy rates including biochemical pregnancy, clinical pregnancy, early pregnancy loss, and ongoing pregnancy, indicating that cycle cancellation due to SARS-CoV-2 infection may not be necessary. Further studies are warranted to verify these findings. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2019YFA0802604), National Natural Science Foundation of China (82130046, 82101747), Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SSMU-ZLCX20180401), Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai Sailing Program (21YF1425000), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36), and Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20161413). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Lithium Pre-Storage Enables High Initial Coulombic Efficiency and Stable Lithium-Enriched Silicon/Graphite Anode.

Application of silicon-based anodes is significantly challenged by low initial Coulombic efficiency (ICE) and poor cyclability. Traditional pre-lithiation reagents often pose safety concerns due to their unstable chemical nature. Achieving a balance between water-stability and high ICE in prelithiated silicon is a critical issue. Here, we present a lithium-enriched silicon/graphite material with an ultra-high ICE of ≥110 % through a high-stable lithium pre-storage methodology. Lithium pre-storage prepared a nano-drilled graphite material with surficial lithium functional groups, which can form chemical bonds with adjacent silicon during high-temperature sintering. This results in an unexpected O-Li-Si interaction, leading to in situ pre-lithiation of silicon nanoparticles and providing high stability in air and water. Additionally, the lithium-enriched silicon/graphite materials impart a combination of high ICE, high specific capacity (620 mAh g-1), and long cycling stability (>400 cycles). This study opens up a promising avenue for highly air- and water-stable silicon anode prelithiation methods.

Oral bacteriome and mycobiome of patients with idiopathic membranous nephropathy with different tongue coatings treated with a Chinese herbal formula.

ETHNOPHARMACOLOGICAL RELEVANCE: Moshen Fuyuan Formula (MSFY) is one of the representative Chinese medicine compound for Idiopathic membranous nephropathy (IMN), that originate from Fang Ji Huang Qi decoction in the Han dynasty. IMN is usually accompanied by different tongue coatings in traditional Chinese medicine (TCM), and tongue microorganisms are important factors affecting the formation of the tongue coating. Recently, oral microbiomes, including bacteria and fungi, have been identified as pivotal factors that contribute to disease development. However, the regulation of oral microbiomes by MSFY has not been defined. AIM OF THE STUDY: In this work, we explore the characteristics of oral bacteria and fungi in IMN patients with different tongue coatings, and clarify the therapeutic effect of MSFY based on oral microbiome. MATERIALS AND METHODS: We enrolled 24 patients with IMN, including 11 with white tongue (IMN-W) and 13 with yellow tongue (IMN-Y), and recruited an additional 10 healthy individuals. Patients with IMN were treated with the MSFY. The oral bacteriome and fungi before and after treatment were detected using full-length 16S rRNA and internal transcribed spacer gene sequencing. RESULTS: The therapeutic effect of MSFY on patients with yellow tongue coating was more significant than that on patients with white tongue coating. In terms of oral bacteriome, Campylobacter bacteria were enriched in patients with yellow tongue and could be a promising biomarker for yellow coating. Enrichment of Veillonella parvula_A may partially account for the therapeutic effect of MSFY. As for oral fungi, Malassezia globosa was enhanced in patients with IMN-W and reduced in patients with IMN-Y. Notably, it was reduced by MSFY. We also found that mycobiome-bacteriome interactions were highly complex and dynamic in patients with IMN. CONCLUSION: The regulation of the dynamic balance between oral fungi and bacteria by MSFY contributes to the treatment of IMN. This study determined the oral bacteriome and mycobiome of patients with IMN with different tongue coatings before and after MSFY treatment, which aids in promoting personalized treatment in clinical TCM and provides direction for investigating the mechanism of Chinese herbal medicines.

[Evidence map analysis of randomized controlled trial of commonly used Chinese patent medicines in treatment of type 2 diabetes mellitus in recent five years].

This study systematically combed the randomized controlled trial(RCT) of Chinese patent medicines in treatment of type 2 diabetes mellitus(T2DM) in recent five years by using the method of evidence map. It understood the distribution and quality of evidence in this field and found the existing Chinese patent medicines in treatment of T2DM and the problems in its research. The study collected the commonly used Chinese patent medicines for the treatment of T2DM from three drug catalogs, retrieved Chinese and English databases to obtain RCT literature related to Chinese patent medicines in recent five years, and extracted information such as sample size, study drug, combination medication, course of treatment, and outcome indicators from the literature. It also conducted quality evaluation based on the Cochrane collaborative network bias risk assessment tool and used charts to display the analysis results. A total of 19 kinds of Chinese patent medicines are collected, of which 13 kinds of Chinese patent medicines are mentioned in 131 articles related to RCT. The literature concerning Shenqi Jiangtang Capsules/Granules, Jinlida Granules, and Xiaoke Pills accounts for a large proportion. Outcome indicators include blood glucose, blood lipids, pancreatic islet cell function, and clinical symptoms. In terms of literature quality, 75 articles have correct random methods, and 1 article performs allocation hiding and blind methods. Therefore, the clinical orientation of Chinese patent medicines for the treatment of T2DM is broad, failing to reflect their own characteristics and lacking safety information. Insufficient attention has been paid to TCM syndrome scores, quality of life, and blood lipid outcome indicators that reflect the characteristics of traditional Chinese medicine(TCM). The number of studies on the treatment of T2DM by Chinese patent medicines varies greatly among varieties, and the quality of the studies is low. It is suggested that the holders of the marketing license of T2DM Chinese patent medicines should carry out a post-marketing re-evaluation of the varieties of traditional Chinese patent medicines for treating T2DM according to the relevant requirements of the State Food and Drug Administration, standardize the clinical positioning, and revise and improve the safety information in the instructions. It is recommended that researchers construct a core indicator dataset for Chinese patent medicine treatment of T2DM, improve the efficacy evaluation system, and develop an experimental plan based on CONSORT before conducting RCT.

Preliminary study on the protective effect of remazolam against sepsis-induced acute respiratory distress syndrome (ARDS).

Background: Sepsis can disrupt immune regulation and lead to acute respiratory distress syndrome (ARDS) frequently. Remazolam, a fast-acting hypnotic drug with superior qualities compared to other drugs, was investigated for its potential protective effects against sepsis-induced ARDS. Methods: Forty Sprague-Dawley rats were randomly divided into four groups, including the sepsis + saline group, sham operation + saline group, sham operation + remazolam group and the sepsis + remazolam group. Lung tissues of rats were extracted for HE staining to assess lung damage, and the wet weight to dry weight (W/D) ratio was calculated. The levels of proinflammatory factors, anti-inflammatory factors, CD4+ and CD8+ T cells in peripheral blood, MDA, MPO, and ATP in the lung tissue were measured by using ELISA. Western blotting was performed to determine the protein expression of HMGB1 in lung tissues. Results: In comparison to the sham operation + saline and sham operation + remazolam groups, the sepsis + saline group exhibited significantly higher values for W/D ratio, lung damage score, IL-1ß, IL-6, TNF-α, PCT, CRP, MDP and MPO, while exhibiting lower levels of CD4+ and CD8+ T lymphocytes, PaO2, PCO2, and ATP. The rats in the sepsis + saline group displayed ruptured alveolar walls and evident interstitial lung edema. However, the rats in the sepsis + remazolam group showed improved alveolar structure. Furthermore, the HMGB1 protein expression in the sepsis + remazolam group was lower than the sepsis + saline group. Conclusion: Remazolam can alleviate the inflammatory response in infected rats, thereby alleviating lung injury and improving immune function, which may be attributed to the reduction in HMGB1 protein expression.

Antiphospholipid syndrome presenting as extensive skin ulcers on unilateral lower extremity: a case report.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by recurrent arterial and venous thrombosis, habitual fetal miscarriages, often accompanied by mild to moderate thrombocytopenia, and persistent moderate-to-high titer positivity for antiphospholipid antibodies (aPLs). However, patients with antiphospholipid antibodies may also present with several nonthrombotic clinical manifestations, such as thrombocytopenia, cardiac valve disease, nephropathy, skin ulcers, or cognitive dysfunction, which are collectively referred to as nonstandard manifestations of APS. Of these, for APS with predominantly cutaneous ulcers, previous reports have focused on APS with combined cutaneous vasculitis, and its medical treatment, rather than cutaneous ulcers with predominantly fatty inflammatory lesions, and the associated surgical treatment. Here, we admitted a relatively rare case of primary APS with extensive skin ulceration of the right lower extremity, without cutaneous vasculitis, in the presence of extensive and severe inflammatory lipoatrophy, carrying anti-ß2-glycoprotein I and lupus anticoagulant, which is reported as follows, with a view to raising awareness of this disease.

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius.

Safflopentsides A-C (1-3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1-3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 µM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

Ion-Exchange-Induced Phase Transition Enables an Intrinsically Air Stable Hydrogarnet Electrolyte for Solid-State Lithium Batteries.

Inferior air stability is a primary barrier for large-scale applications of garnet electrolytes in energy storage systems. Herein, a deeply hydrated hydrogarnet electrolyte generated by a simple ion-exchange-induced phase transition from conventional garnet, realizing a record-long air stability of more than two years when exposed to ambient air is proposed. Benefited from the elimination of air-sensitive lithium ions at 96 h/48e sites and unobstructed lithium conduction path along tetragonal sites (12a) and vacancies (12b), the hydrogarnet electrolyte exhibits intrinsic air stability and comparable ion conductivity to that of traditional garnet. Moreover, the unique properties of hydrogarnet pave the way for a brand-new aqueous route to prepare lithium metal stable composite electrolyte on a large-scale, with high ionic conductivity (8.04 × 10-4 S cm-1), wide electrochemical windows (4.95 V), and a high lithium transference number (0.43). When applied in solid-state lithium batteries (SSLBs), the batteries present impressive capacity and cycle life (164 mAh g-1 with capacity retention of 89.6% after 180 cycles at 1.0C under 50 °C). This work not only designs a new sort of hydrogarnet electrolyte, which is stable to both air and lithium metal but also provides an eco-friendly and large-scale fabrication route for SSLBs.

Acupuncture for obesity and related diseases: Insight for regulating neural circuit.

Obesity is defined as abnormal or excessive fat accumulation that may impair health. Obesity is associated with numerous pathological changes including insulin resistance, fatty liver, hyperlipidemias, and other obesity-related diseases. These comorbidities comprise a significant public health threat. Existing anti-obesity drugs have been limited by side effects that include depression, suicidal thoughts, cardiovascular complications and stroke. Acupuncture treatment has been shown to be effective for treating obesity and obesity-related conditions, while avoiding side effects. However, the mechanisms of acupuncture in treating obesity-related diseases, especially its effect on neural circuits, are not well understood. A growing body of research has studied acupuncture's effects on the endocrine system and other mechanisms related to the regulation of neural circuits. In this article, recent research that was relevant to the use of acupuncture to treat obesity and obesity-related diseases through the neuroendocrine system, as well as some neural circuits involved, was summarized. Based on this, acupuncture's potential ability to regulate neural circuits and its mechanisms of action in the endocrine system were reviewed, leading to a deeper mechanistic understanding of acupuncture's effects and providing insight and direction for future research about obesity. Please cite this article as: Jiang LY, Tian J, Yang YN, Jia SH, Shu Q. Acupuncture for obesity and related diseases: insight for regulating neural circuit. J Integr Med. 2024; 22(2): 93-101.

BBR affects macrophage polarization via inhibition of NF-κB pathway to protect against T2DM-associated periodontitis.

BACKGROUND AND OBJECTIVE: Periodontitis is intimately associated with the development of various systemic diseases, among which type 2 diabetes mellitus (T2DM) has a bidirectional relationship with the pathogenesis of periodontitis. The objective of the present work was to investigate the role of berberine (BBR) in periodontitis with T2DM and related mechanisms. METHODS: The mRNA expression of macrophage polarization-related factors in the microenvironment of periodontal inflammation was detected using real-time quantitative PCR (RT-qPCR). The experimental periodontitis model was constructed in wild-type (WT) and T2DM (db/db) mice, which were administered BBR after 7 days of modeling. Alveolar bone loss (ABL) in each group of mice was measured utilizing micro-computed tomography images. RT-qPCR was performed to analyze the levels of macrophage polarization-related factors in mouse gingiva. Lastly, using western blotting and RT-qPCR, the signaling pathway of BBR affecting macrophage polarization in the microenvironment of periodontitis was explored. RESULTS: BBR inhibited M1 polarization and stimulated M2 polarization in the periodontitis microenvironment. BBR decreased ABL in the WT and T2DM periodontitis models. And BBR reduced the production of proinflammatory cytokines and increased anti-inflammatory cytokine expression in the gingiva of WT and T2DM model mice. Ultimately, BBR mediates its anti-inflammatory effects on periodontitis through inhibition of the NF-κB pathway. CONCLUSIONS: BBR had a therapeutic effect on T2DM-associated periodontitis via inhibiting the NF-κB pathway to affect macrophage polarization, which may have implications for the new pharmacological treatment of T2DM-associated periodontitis.

Enhancing ß-cell function and identity in type 2 diabetes: The protective role of Coptis deltoidea C. Y. Cheng et Hsiao via glucose metabolism modulation and AMPK signaling activation.

BACKGROUND: Abnormalities in glucose metabolism may be the underlying cause of ß-cell dysfunction and identity impairment resulting from high glucose exposure. In China, Coptis deltoidea C. Y. Cheng et Hsiao (YL) has demonstrated remarkable hypoglycemic effects. HYPOTHESIS/PURPOSE: To investigate the hypoglycemic effect of YL and determine the mechanism of YL in treating diabetes. METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of YL. YL was administrated once daily for 8 weeks. The hypoglycemic effect of YL was assessed by fasting blood glucose, an oral glucose tolerance test, insulin levels, and other indexes. The underlying mechanism of YL was examined by targeting glucose metabolomics, western blotting, and qRT-PCR. Subsequently, the binding capacity between predicted AMP-activated protein kinase (AMPK) and important components of YL (Cop, Ber, and Epi) were validated by molecular docking and surface plasmon resonance. Then, in AMPK knockdown MIN6 cells, the mechanisms of Cop, Ber, and Epi were inversely confirmed through evaluations encompassing glucose-stimulated insulin secretion, markers indicative of ß-cell identity, and the examination of glycolytic genes and products. RESULTS: YL (0.9 g/kg) treatment exerted notable hypoglycemic effects and protected the structural integrity and identity of pancreatic ß-cells. Metabolomic analysis revealed that YL inhibited the hyperactivated glycolysis pathway in diabetic mice, thereby regulating the products of the tricarboxylic acid cycle. KEGG enrichment revealed the intimate relationship of this process with the AMPK signaling pathway. Cop, Ber, and Epi in YL displayed high binding affinities for AMPK protein. These compounds played a pivotal role in preserving the identity of pancreatic ß-cells and amplifying insulin secretion. The mechanism underlying this process involved inhibition of glucose uptake, lowering intracellular lactate levels, and elevating acetyl coenzyme A and ATP levels through AMPK signaling. The use of a glycolytic inhibitor corroborated that attenuation of glycolysis restored ß-cell identity and function. CONCLUSION: YL demonstrates significant hypoglycemic efficacy. We elucidated the potential mechanisms underlying the protective effects of YL and its active constituents on ß-cell function and identity by observing glucose metabolism processes in pancreatic tissue and cells. In this intricate process, AMPK plays a pivotal regulatory role.

Effects of chemical oxygen demand and chloramphenicol on attached microalgae growth: Physicochemical properties and microscopic mass transfer in biofilm.

During the wastewater treatment and resource recovery process by attached microalgae, the chemical oxygen demand (COD) can cause biotic contamination in algal culture systems, which can be mitigated by adding an appropriate dosage of antibiotics. The transport of COD and additive antibiotic (chloramphenicol, CAP) in algal biofilms and their influence on algal physiology were studied. The results showed that COD (60 mg/L) affected key metabolic pathways, such as photosystem II and oxidative phosphorylation, improved biofilm autotrophic and heterotrophic metabolic intensities, increased nutrient demand, and promoted biomass accumulation by 55.9 %, which was the most suitable COD concentration for attached microalgae. CAP (5-10 mg/L) effectively stimulated photosynthetic pigment accumulation and nutrient utilization in pelagic microalgal cells. In conclusion, controlling the COD concentration (approximately 60 mg/L) in the medium and adding the appropriate CAP concentration (5-10 mg/L) are conducive to improving attached microalgal biomass production and resource recovery potential from wastewater.

Gut microbiota-based discovery of Houttuyniae Herba as a novel prebiotic of Bacteroides thetaiotaomicron with anti-colitis activity.

Ulcerative colitis (UC) represents an inflammatory disease characterized by fluctuations in severity, posing substantial challenges in treatment. The gut microbiota plays a pivotal role in the pathogenesis of UC. This study sought to identify drugs specifically targeting the gut microbiota to mitigate UC. We initiated a meta-analysis on gut microbiota in UC patients to identify UC-associated bacterial strains. Subsequently, we screened 164 dietary herbal medicines in vitro to identify potential prebiotics for the UC-associated bacterium, Bacteroides thetaiotaomicron. The DSS-induced colitis mouse model was utilized to evaluate the anti-colitis efficacy of the identified dietary herbal medicine. Full-length 16 S rRNA amplicon sequencing was employed to observe changes in gut microbiota following dietary herbal medicine intervention. The relative abundance of Bacteroides was notably diminished in UC patients compared to their healthy counterparts. B. thetaiotaomicron exhibited an inverse relationship with UC symptoms, indicating its potential as an anti-colitis agent. In vitro assessments revealed that H. Herba significantly bolstered the proliferation of B. thetaiotaomicron. Further experiments showed that treating DSS-induced mice with an aqueous extract of H. Herba considerably alleviated colitis indicators such as weight loss, colon shortening, disease activity score (DAI), and systemic inflammation. Microbial analysis revealed B. thetaiotaomicron as the sole bacterium substantially augmented by H. Herba in vivo. Overall H. Herba emerges as a promising prebiotic for B. thetaiotaomicron, offering significant anti-colitis benefits. Employing a gut microbiota-centric approach proves valuable in the quest for drug discovery.This study provides a new paradigm for drug discovery that targets the gut microbiota to treat UC.

[Clinical and genetic analysis of a child with Canavan disease due to compound heterozygous variants of ASPA gene].

OBJECTIVE: To analyze the clinical phenotype and genetic characteristics for a child with Canavan disease. METHODS: A child who was admitted to the Children's Hospital Affiliated to Shandong University on April 9, 2021 for inability to uphold his head for 2 months and increased muscle tone for one week was subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing. RESULTS: Genetic testing revealed that the child has harbored compound heterozygous variants of the ASPA gene, including a paternally derived c.556_559dupGTTC (p. L187Rfs*5) and a maternally derived c.919delA (p. S307Vfs*24). Based on the guidelines from the American College of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2_Supporting+PM3). CONCLUSION: The c.556_559dupGTTC (p.L187Rfs*5) and c.919delA (p.S307Vfs*24) compound heterozygous variants of the ASPA gene probably underlay the pathogenesis of Canavan disease in this child.

Jinkui Shenqi pills ameliorate diabetes by regulating hypothalamic insulin resistance and POMC/AgRP expression and activity.

BACKGROUND: Research on the imbalance of proopiomelanocortin (POMC)/agouti-related protein (AgRP) neurons in the hypothalamus holds potential insights into the pathophysiology of diabetes. Jinkui Shenqi pills (JSP), a prevalent traditional Chinese medicine, regulate hypothalamic function and treat diabetes. PURPOSE: To investigate the hypoglycemic effect of JSP and explore the probable mechanism in treating diabetes. METHODS: A type 2 diabetes mouse model was used to investigate the pharmacodynamics of JSP. The glucose-lowering efficacy of JSP was assessed through various metrics including body weight, food consumption, fasting blood glucose (FBG), serum insulin levels, and an oral glucose tolerance test (OGTT). To elucidate the modulatory effects of JSP on hypothalamic mechanisms, we quantified the expression and activity of POMC and AgRP and assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (AKT)/forkhead box O1 (FOXO1) pathway in diabetic mice via western blotting and immunohistochemistry. Additionally, primary hypothalamic neurons were exposed to high glucose and palmitic acid levels to induce insulin resistance, and the influence of JSP on POMC/AgRP protein expression and activation was evaluated by PI3K protein inhibition using western blotting and immunofluorescence. RESULTS: Medium- and high-dose JSP treatment effectively inhibited appetite, resulting in a steady declining trend in body weight, FBG, and OGTT results in diabetic mice (p < 0.05). These JSP groups also had significantly increased insulin levels (p < 0.05). Importantly, the medium-dose group exhibited notable protection of hypothalamic neuronal and synaptic structures, leading to augmentation of dendritic length and branching (p < 0.05). Furthermore, low-, medium-, and high-dose JSP groups exhibited increased phosphorylated (p) INSR, PI3K, pPI3K, AKT, and pAKT expression, as well as decreased FOXO1 and increased pFOXO1 expression, indicating improved hypothalamic insulin resistance in diabetic mice (p < 0.05). Treatment with 10% JSP-enriched serum produced a marked elevation of both expression and activation of POMC (p < 0.05), with a concurrent reduction in AgRP expression and activation within primary hypothalamic neurons (p < 0.05). Intriguingly, these effects could be attributed to the regulatory dynamics of PI3K activity. CONCLUSION: Our findings suggest that JSP can ameliorate diabetes by regulating POMC/AgRP expression and activity. The insulin-mediated PI3K/AKT/FOXO1 pathway plays an important regulatory role in this intricate process.

Potential efficacy and mechanism of eight mild-natured and bitter-flavored TCMs based on gut microbiota: A review.

The mild-natured and bitter-flavored traditional Chinese medicines (MB-TCMs) are an important class of TCMs that have been widely used in clinical practice and recognized as safe long-term treatments for chronic diseases. However, as an important class of TCMs, the panorama of pharmacological effects and the mechanisms of MB-TCMs have not been systemically reviewed. Compelling studies have shown that gut microbiota can mediate the therapeutic activity of TCMs and help to elucidate the core principles of TCM medicinal theory. In this systematic review, we found that MB-TCMs commonly participated in the modulation of metabolic syndrome, intestinal inflammation, nervous system disease and cardiovascular system disease in association with promoting the growth of beneficial bacteria Bacteroides, Akkermansia, Lactobacillus, Bifidobacterium, Roseburia as well as inhibiting the proliferation of harmful bacteria Helicobacter, Enterococcus, Desulfovibrio and Escherichia-Shigella. These alterations, correspondingly, enhance the generation of protective metabolites, mainly including short-chain fatty acids (SCFAs), bile acid (BAs), 5-hydroxytryptamine (5-HT), indole and gamma-aminobutyric acid (GABA), and inhibit the generation of harmful metabolites, such as proinflammatory factors trimethylamine oxide (TAMO) and lipopolysaccharide (LPS), to further exert multiplicative effects for the maintenance of human health through several different signaling pathways. Altogether, this present review has attempted to comprehensively summarize the relationship between MB-TCMs and gut microbiota by establishing the TCMs-gut microbiota-metabolite-signaling pathway-diseases axis, which may provide new insight into the study of TCM medicinal theories and their clinical applications.

Mitochondrial uncoupler and retinoic acid synergistically induce differentiation and inhibit proliferation in neuroblastoma.

Neuroblastoma is a leading cause of death in childhood cancer cases. Unlike adult malignancies, which typically develop from aged cells through accumulated damage and mutagenesis, neuroblastoma originates from neural crest cells with disrupted differentiation. This distinct feature provides novel therapeutic opportunities beyond conventional cytotoxic methods. Previously, we reported that the mitochondrial uncoupler NEN (niclosamide ethanolamine) activated mitochondria respiration to reprogram the epigenome, promoting neuronal differentiation. In the current study, we further combine NEN with retinoic acid (RA) to promote neural differentiation both in vitro and in vivo. The treatment increased the expression of RA signaling and neuron differentiation-related genes, resulting in a global shift in the transcriptome towards a more favorable prognosis. Overall, these results suggest that the combination of a mitochondrial uncoupler and the differentiation agent RA is a promising therapeutic strategy for neuroblastoma.