Research Status and Trends of Traditional Chinese Medicine Therapeutic Formulae for Coronary Heart Disease Scientometrics Research.

Aim of the Study: This study analyzes research on TCM formulae in CHD over the past 30 years, using VOSviewer and CiteSpace. It aims to highlight key trends and hotspots in the field. Materials and Methods: The core database of Web of Science was collected, and the search time range was from the establishment of the database to the present (August 2023) for the literature related to the study of TCM prescriptions in CHD, and the information on the number of literature, countries, journals, authors, institutions, keywords were summarized by applying the software VOSviewer and CiteSpace. Results: A total of 135 kinds of literature were included. The number of published journal papers on research on TCM therapeutic formulae for CHD showed an upward trend; China was the most prolific country in this field; the largest number of papers were published in Evid Based Complement Alternat Med, MEDICINE; the average number of citations for authors and institutional analysis revealed that Xu Hao of China Academy of Traditional Chinese Medicine, Mao Jingyuan of Tianjin University of Traditional Chinese Medicine, and Shang Hongcai of Beijing University of Traditional Chinese Medicine constituted the core team of researchers studying the study of TCM formulae for CHD; the keyword analysis suggests that there are mainly 42 specifically named TCM formulae for the treatment of CHD, which are classified into a total of 7 major categories, and the research direction is mainly in the clinical efficacy study of different TCM therapeutic formulae and other aspects. Conclusion: This study shows that there are more types of TCM therapeutic formulae for CHD, and the related research has a good prospect. It is foreseeable that more relevant research results will rely on the study of network pharmacology, signalling pathways, and action targets of TCM therapeutic formulae.

Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial.

BACKGROUND: Acute gouty arthritis (AGA) is an inflammatory joint disease with a high prevalence. Typical medical interventions, including nonsteroidal anti-inflammatory drugs, colchicine and glucocorticoids, can have serious adverse reactions. Huzhang Granule (HZG), a compound Chinese herbal medicine, has been used to treat AGA for more than 30 years with satisfactory effects and no significant adverse reactions. However, the efficacy and safety of HZG in AGA patients remains unknown. OBJECTIVE: The present investigation was designed to examine the efficacy and safety profile of HZG in managing AGA patients. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The current study was conducted as a noninferiority, randomized controlled clinical trial on 180 eligible enrolled participants. Participants were randomly assigned into the HZG and etoricoxib groups. Treatments were administered for 5 d, during which the HZG group received HZG and placebo etoricoxib, while the etoricoxib group received etoricoxib and placebo HZG in the same ratio (1:1). MAIN OUTCOME MEASURES: The primary outcome was pain experienced by the patient in the gout-afflicted joint from days 2 to 5 of the treatment window. The pain level was measured via a visual analogue scale, ranging from 0 mm to 100 mm. The secondary outcomes comprised joint tenderness and swelling, reduction of inflammatory biomarkers, and the patient's and investigator's global evaluations of therapeutic response. RESULTS: The mean reduction in pain was -51.22 mm (95% confidence interval [CI], [-53.42, -49.03] mm) for the HZG and -52.00 mm (95% CI, [-54.06, -49.94] mm) for the etoricoxib groups. The mean difference between the two groups was 0.78 mm (95% CI, [-2.25, 3.81] mm). All additional efficacy endpoints, covering decreased inflammation and pain relief, yielded compelling proof of noninferiority. Patients in the HZG group exhibited a comparatively lower rate of adverse events compared to those in the etoricoxib group (4.44% vs 13.33%; P ≤ 0.05). CONCLUSION: HZG and etoricoxib groups demonstrated similar levels of analgesic effectiveness. The safety and efficacy of HZG indicates that it can be used as a potential therapeutic option for treating AGA. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2000036970). Please cite this article as: Wang H, Chen ST, Ding XJ, Kuai L, Hua L, Li X, Wang YF, Zhang M, Li B, Wang RP, Zhou M. Efficacy and safety of Huzhang Granule, a compound Chinese herbal medicine, for acute gouty arthritis: A double-blind, randomized controlled trial. J Integr Med. 2024; 22(3): 270-278.

Therapeutic effects of the Qingre-Qushi recipe on atopic dermatitis through the regulation of gut microbiota and skin inflammation.

Accumulating evidence has highlighted a strong association between gut microbiota and the occurrence, development, prevention, and treatment of atopic dermatitis (AD). The regulation of gut microbial dysbiosis by oral traditional Chinese medicine (TCM) has garnered significant attention. In the treatment of AD, the TCM formula Qingre-Qushi Recipe (QRQS) has demonstrated clinical efficacy. However, both the therapeutic mechanisms of QRQS and its impact on gut microbiota remain unclear. Thus, our study aimed to assess the efficacy of QRQS and evaluate its influence on the composition and diversity of gut microbiota in AD animal models. First, we investigated the therapeutic effect of QRQS on AD using two animal models: filaggrin-deficient mice (Flaky tail, ft/ft) and MC903-induced AD-like mice. Subsequently, we explored its influence on the composition and diversity of gut microbiota. Our results demonstrated that QRQS treatment ameliorated the symptoms in both ft/ft mice and MC903-induced AD-like mice. It also reduced the levels of serum IgE and pro-inflammatory cytokines, including IL-1ß, IL-4, IL-5, IL-9, IL-13, IL-17A, and TNF-α. Furthermore, QRQS remarkably regulated gut microbiota diversity by increasing Lactobacillaceae and decreasing Bacteroidales. The inflammatory factors in peripheral serum of ft/ft mice showed a close correlation with gut microbiota, as determined using the Spearman correlation coefficient. Additionally, PICRUSt analysis revealed an enrichment in ascorbate and aldarate metabolism, fatty acid metabolism and biosynthesis, and propanoate metabolism in the QRQS group compared to the ft/ft group. Finally, we identified liquiritin as the primary active ingredient of QRQS using ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UPLC-HRMS). Our findings revealed that QRQS improved AD-like symptoms and alleviated skin inflammation in ft/ft and MC903-induced mice. This suggests that modulating the gut microbiota may help elucidate its anti-inflammation activation mechanism, highlighting a new therapeutic strategy that targets the intestinal flora to prevent and treat AD.

Sarsasapogenin regulates the immune microenvironment through MAPK/NF-kB signaling pathway and promotes functional recovery after spinal cord injury.

Spinal cord injury (SCI) occurs as a result of traumatic events that damage the spinal cord, leading to motor, sensory, or autonomic function impairment. Sarsasapogenin (SA), a natural steroidal compound, has been reported to have various pharmacological applications, including the treatment of inflammation, diabetic nephropathy, and neuroprotection. However, the therapeutic efficacy and underlying mechanisms of SA in the context of SCI are still unclear. This research aimed to investigate the therapeutic effects and mechanisms of SA against SCI by integrating network pharmacology analysis and experimental verification. Network pharmacology results suggested that SA may effectively treat SCI by targeting key targets such as TNF, RELA, JUN, MAPK14, and MAPK8. The underlying mechanism of this treatment may involve the MAPK (JNK) signaling pathway and inflammation-related signaling pathways such as TNF and Toll-like receptor signaling pathways. These findings highlight the therapeutic potential of SA in SCI treatment and provide valuable insights into its molecular mechanisms of action. In vivo experiments confirmed the reparative effect of SA on SCI in rats and suggested that SA could repair SCI by modulating the immune microenvironment. In vitro experiments further investigated how SA regulates the immune microenvironment by inhibiting the MAPK/NF-kB pathways. Overall, this study successfully utilized a combination of network pharmacology and experimental verification to establish that SA can regulate the immune microenvironment via the MAPK/NF-kB signaling pathway, ultimately facilitating functional recovery from SCI. Furthermore, these findings emphasize the potential of natural compounds from traditional Chinese medicine as a viable therapy for SCI treatment.

Efficacy of Black Gold, Delicate Pulse Light, Super Photon Skin Rejuvenation for Pigmented Dermatoses.

Context: Pigmented dermatoses are skin diseases characterized by pigmentation changes in the skin's surface due to abnormal melanocyte production. Photon-skin-rejuvenation technology can be effective for the management of facial pigmented dermatoses. Black Gold Delicate Pulse Light (DPL) Super Photon Skin Rejuvenation therapy is a new technology based on traditional photo rejuvenation. Objective: The study intended to evaluate the therapeutic efficacy of DPL therapy in the management of targeted pigmented skin diseases, such as melasma, solar lentigines, and postinflammatory hyperpigmentation. Design: The research team conducted a prospective cohort study. Setting: The study took place at Department of Dermatology, Affiliated Hospital of Shaoxing University, Shaoxing, China. Participants: Participants were 130 patients with facial pigmented dermatoses treated at the hospital between February 2021 and December 2021. Interventions: The research team assigned participants to one of two groups, with 65 participants in each group: (1) the control group, the intense pulsed light (IPL) group, who received IPL treatment, and (2) the intervention group, the DPL group, who received black gold DPL super photon skin rejuvenation. Both groups received the treatments once a month for 6 months. Outcome Measures: At baseline and postintervention for both groups, the research team: (1) collected 5 ml of fasting venous blood from participants and measured serum concentrations of melatonin (MEL), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) using enzyme-linked immunosorbent assay (ELISA); (2) assessed the degree of reduction of facial pigmentation using the Visia skin test and each participant's clinical results and calculated total efficacy; and (3) monitored and recorded adverse events. Results: Compared to the IPL group, the DPL group: (1) had greater symptom mitigation of the facial pigmented dermatosis, as evinced by significantly lower serum MEL (P = .001) and ET-1 (P = .020) concentrations and higher VEGF levels (P = .001); (2) for participants with freckles (P = .045), cafe-au-lait spots (P = .021), or post-acne hyperpigmentation (P = .029), had a significantly higher total efficacy; and (3) had a lower incidence of adverse events (P = .041). Conclusions: Black Gold DPL Super Photon Skin Rejuvenation offers a significantly higher safety profile and treatment efficacy for pigmented-skin diseases compared to IPL treatment. These promising results suggest potential for its use in clinical practice, but clinical adoption requires future trials.

A comprehensive review of Tripterygium wilfordii hook. f. in the treatment of rheumatic and autoimmune diseases: Bioactive compounds, mechanisms of action, and future directions.

Rheumatic and autoimmune diseases are a group of immune system-related disorders wherein the immune system mistakenly attacks and damages the body's tissues and organs. This excessive immune response leads to inflammation, tissue damage, and functional impairment. Therapeutic approaches typically involve medications that regulate immune responses, reduce inflammation, alleviate symptoms, and target specific damaged organs. Tripterygium wilfordii Hook. f., a traditional Chinese medicinal plant, has been widely studied in recent years for its application in the treatment of autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis. Numerous studies have shown that preparations of Tripterygium wilfordii have anti-inflammatory, immunomodulatory, and immunosuppressive effects, which effectively improve the symptoms and quality of life of patients with autoimmune diseases, whereas the active metabolites of T. wilfordii have been demonstrated to inhibit immune cell activation, regulate the production of inflammatory factors, and modulate the immune system. However, although these effects contribute to reductions in inflammatory responses and the suppression of autoimmune reactions, as well as minimize tissue and organ damage, the underlying mechanisms of action require further investigation. Moreover, despite the efficacy of T. wilfordii in the treatment of autoimmune diseases, its toxicity and side effects, including its potential hepatotoxicity and nephrotoxicity, warrant a thorough assessment. Furthermore, to maximize the therapeutic benefits of this plant in the treatment of autoimmune diseases and enable more patients to utilize these benefits, efforts should be made to strengthen the regulation and standardized use of T. wilfordii.

Eremophilane and cadinane sesquiterpenoids from the fruits of Alpinia oxyphylla and their anti-inflammatory activities.

The fruits of Alpinia oxyphylla have been used for centuries in China as both edible resources and traditional Chinese medicine. In order to identify structurally interesting and bioactive constituents from the fruits of A. oxyphylla, bioassay-guided fractionation and purification of the crude extracts were performed, which led to the isolation of 38 sesquiterpenoids, including six previously undescribed eremophilane sesquiterpenoids (1-6), six new cadinane sesquiterpenoids (23-24, 26-29), and 26 known analogues (7-22, 25 and 31-38). The structures of these compounds were elucidated by comprehensive spectroscopic data analysis, single crystal X-ray diffraction, quantum chemistry calculations (13C-NMR and ECD), and Mo2(OAc)4 reaction. Several of the isolated compounds (8, 13, 17, 18, 30, 31 and 35) showed moderate to strong inhibition of the secretion of cytokines (NO, TNF-α and IL-6) in LPS-stimulated BV-2 cells. Furthermore, western blot, immunofluorescence, and real-time PCR assays indicated that 18 could down-regulate the mRNA levels of TNF-α, IL-6, COX-2, and iNOS and the protein expression of COX-2 and iNOS. Meanwhile, 18 was able to partially inhibit the phosphorylation of ERK1/2, JNK, and p38. Thus, the discovery of structurally diverse anti-inflammatory sesquiterpenoids from the fruits of A. oxyphylla in this study could benefit the further development and utilization of this plant.

Binding of Cd(II) to birnessite and fulvic acid organo-mineral composites and controls on Cd(II) availability.

Manganese oxide minerals (MnOs) are major controls on cadmium (Cd) mobility and fate in the environment. However, MnOs are commonly coated with natural organic matter (OM), and the role of this coating in the retention and availability of harmful metals remains unclear. Herein, organo-mineral composites were synthesized using birnessite (BS) and fulvic acid (FA), during coprecipitation with BS and adsorption to preformed BS with two organic carbon (OC) loadings. The performance and underlying mechanism of Cd(II) adsorption by resulting BS-FA composites were explored. Consequently, FA interactions with BS at environmentally representative (5 wt% OC) increase Cd(II) adsorption capacity by 15.05-37.39% (qm = 156.5-186.9 mg g-1), attributing to the enhanced dispersion of BS particles by coexisting FA led to significant increases in specific surface area (219.1-254.8 m2 g-1). Nevertheless, Cd(II) adsorption was notably inhibited at a high OC level (15 wt%). This might have derived from the supplementation of FA decreased pore diffusion rate and generated Mn(II/III) competition for vacancy sites. The dominant Cd(II) adsorption mechanism was precipitation with minerals (Cd(OH)2), and complexation with Mn-O groups and acid oxygen-containing functional groups of FA. In organic ligand extractions, the exchange Cd content decreased by 5.63-7.93% with low OC coating (5 wt%), but increased to 33.13-38.97% at a high OC level (15 wt%). These findings help better understand the environmental behavior of Cd under the interactions of OM and Mn minerals, and provide a theoretical basis for organo-mineral composite remediation of Cd-contaminated water and soil.

Current status and trends of artificial intelligence research on the four traditional Chinese medicine diagnostic methods: a scientometric study.

Background: With the development of technology and the renewal of traditional Chinese medicine (TCM) diagnostic equipment, artificial intelligence (AI) has been widely applied in TCM. Numerous articles employing this technology have been published. This study aimed to outline the knowledge and themes trends of the four TCM diagnostic methods to help researchers quickly master the hotspots and trends in this field. Four TCM diagnostic methods is a TCM diagnostic method through inspection, listening, smelling, inquiring and palpation, the purpose of which is to collect the patient's medical history, symptoms and signs. Then, it provides an analytical basis for later disease diagnosis and treatment plans. Methods: Publications related to AI-based research on the four TCM diagnostic methods were selected from the Web of Science Core Collection, without any restriction on the year of publication. VOSviewer and Citespace were primarily used to create graphical bibliometric maps in this field. Results: China was the most productive country in this field, and Evidence-Based Complementary and Alternative Medicine published the largest number of related papers, and the Shanghai University of Traditional Chinese Medicine is the dominant research organization. The Chengdu University of Traditional Chinese Medicine had the highest average number of citations. Jinhong Guo was the most influential author and Artificial Intelligence in Medicine was the most authoritative journal. Six clusters separated by keywords association showed the range of AI-based research on the four TCM diagnostic methods. The hotspots of AI-based research on the four TCM diagnostic methods included the classification and diagnosis of tongue images in patients with diabetes and machine learning for TCM symptom differentiation. Conclusions: This study demonstrated that AI-based research on the four TCM diagnostic methods is currently in the initial stage of rapid development and has bright prospects. Cross-country and regional cooperation should be strengthened in the future. It is foreseeable that more related research outputs will rely on the interdisciplinarity of TCM and the development of neural networks models.

Hydrocarbons removal and microbial community succession in petroleum-contaminated soil under hydrogen peroxide treatment.

Chemical oxidation as a pretreatment step coupled with bioremediation for petroleum-contaminated soil may pose serious impacts on indigenous microorganisms and the available nutrients. Petroleum-contaminated soil were treated by hydrogen peroxide (H2O2) at initial concentrations of 105 mM (HH), 21 mM (HL), and 105 mM in three equal amounts (HT) without adding any external catalyst. The contents of total petroleum hydrocarbons (TPH) and dissolved nutrients (total organic compounds, nitrogen, and phosphate), and the indigenous bacteria community succession (analyzed by high-throughput sequencing of 16S rDNA) were investigated over 50 days. Compared to the control treatment without H2O2 addition, H2O2 treatments for the petroleum-contaminated soil significantly promoted the TPH removal especially in the first 4 days and impacted the contents of dissolved nutrients. Both of chemical oxidation and nutrients contributed to microbial community structure changes in alpha diversity. Although the soil microbial community structure had undergone significant changes after different chemical oxidation pretreatments, Firmicutes, Proteobacteria, Gemmatimonadetes, and Actinobacteria were the main bacterial phyla. Compared with adding H2O2 at one time, H2O2 added in stepwise was beneficial to indigenous bacterial diversity recovery and TPH removal. H2O2 oxidation treatments showed a great influence on the microbial community structures in the start-up stage, while recovery time rather than the oxidation treatments presented greater effects on the composition of the microbial community structure with the incubation time extended. Therefore, adding H2O2 as pretreatment for petroleum-contaminated soil showed little effect on the structure of soil indigenous microbial community from a long-term scale, and was conducive to the continuous removal of TPH by indigenous microorganisms.

An Overview of Systematic Reviews: Acupuncture in the Treatment of Essential Hypertension.

Objective: Acupuncture treatment is widely used for essential hypertension (EH), and numerous systematic reviews on acupuncture for EH have been published. This article provides an overview of the effectiveness and safety of acupuncture for EH and assesses the quality of reports, methodological bias, quality of evidence and risk of bias for inclusion in the evaluation. Methods: Two researchers independently computer searched Pubmed, EMbase, The Cochrane library, WOS, CBM, CNKI, Wangfang Data, VIP and other Chinese and English databases with a search time frame from the date of creation to 13th October 2022; and independently screened systematic reviews of acupuncture therapy for EH; and finally The Report Quality Assessment Tool (PRISMA 2020), Methodological Quality Assessment Tool (AMSTAR2), Grading of Evidence Assessment Tool (GRADE), and Bias Assessment Tool (ROBIS) were used independently to assess the bias of the included literature. Results: A total of 11 systematic reviews were included. The included studies mainly reported on outcome indicators such as efficiency rate, end SBP, end DBP, SBP change value, DBP change value, etc. Deficiencies in the quality of PRISMA 2020 reporting were mainly in the areas of independent screening by multiple researchers, use of GRADE for analysis, early registration, description of conflict of interest, and public access to information; the results of the AMSTAR 2 tool evaluation were mostly were very low, and of the 16 entries affecting the methodological quality of the systematic evaluation, entries 2/3/4/5/12/16 had the greatest methodological bias; GRADE assessed the quality of evidence for key outcome indicators, with a few being low and all others being very low; and ROBIS reported a high level of bias in the literature. Conclusion: Current acupuncture has some efficacy in the treatment of essential hypertension, but its quality of evidence is low. It is hoped that the quality of relevant literature reporting, methodological quality, quality of evidence, and bias will improve.

Polyhydric Stigmastane-Type Steroids Derivative from Vernonia amygdalina and Their Anti-Neuroinflammatory Activity.

Vernonia amygdalina Del. is a traditional medicinal plant and vegetable originating from tropical Africa. The phytochemical investigation of V. amygdalina led to eight undescribed polyhydric stigmastane-type steroids, vernonin M-T (1-8). Their gross structures and stereochemistry were elucidated by HR-ESI-MS, 1D and 2D NMR spectra, X-ray diffraction, quantum chemical computation of the ECD spectrum, and the in situ dimolybdenum CD method. The anti-neuroinflammatory activity of the isolated compounds was performed in BV-2 microglia cells. As a result, compound 1 displayed a notable anti-neuroinflammatory effect via suppressing the LPS-induced IκB degradation and restricting the activation of the PI3K/AKT and p38 MAPK pathways.

Tautomeric phytosterols from Vernonia amygdalina Delile and their anti-cervical cancer activity.

Vernonia amygdalina Delile is generally used as green vegetables for cuisine in Nigeria and health tea or products in southeast of china. It was also used as folk medicine for the treatment of anti-helminth, febrifuge, digestive tonic and wounds. In this study, eleven undescribed phytosterols (1-2, 4-12) and six known analogues (3, 13-17) were isolated from the stems of V. amygdalina. Their structures including absolute configurations were elucidated by comprehensive spectroscopic methods (1D and 2D NMR, HRESIMS), X-ray diffraction and comparison of their ECD spectra. Besides, the tautomerism of phytosterols (1, 3-6, 12-17) with hemiacetal moiety were analyzed by solution NMR with different deuterated solvent and variable-temperature experiments. In addition, the cytotoxic activities of isolates against HeLa cells were evaluated. As a result, compound 10 exhibited the most potent anti-cervical cancer activity with the IC50 of 22.44 µM. Mechanism studies indicated that 10 triggered HeLa cells apoptosis through activating caspase signaling pathway. Furthermore, 10 could arrest the cell cycle in S phase and suppress the activation of the PI3K/AKT/mTOR pathway, leading to the inhibition of HeLa cells proliferation.

Seco-polyprenylated acylphloroglucinols from Hypericum elodeoides induced cell cycle arrest and apoptosis in MCF-7 cells via oxidative DNA damage.

Four undescribed seco-polyprenylated acylphloroglucinols (seco-PAPs), elodeoidesones A-D (1-4), were characterized from Hypericum elodeoides. Compound 1 represents the 1,6-seco-PAPs with fascinating 5/5 fused ring, while 2-4 possess a 1,2-seco-PAPs skeleton with a five-membered lactone core. Their structures including absolute configurations were established by spectroscopic analyses and quantum chemical computations. A possible biosynthetic pathway of 1-4 from normal PAPs was proposed. All the isolates were investigated for their cytotoxicity against tumor cells. Notably, 1 inhibited the proliferation of MCF-7 cells with the IC50 value of 7.34 µM. Mechanism investigation indicated that 1 induced MCF-7 cells apoptosis by blocking cell cycle at S phase via inducing oxidative DNA damage.

Chitosan-Gelatin-EGCG Nanoparticle-Meditated LncRNA TMEM44-AS1 Silencing to Activate the P53 Signaling Pathway for the Synergistic Reversal of 5-FU Resistance in Gastric Cancer.

Chemoresistance is one of the leading causes of therapeutic failure in gastric cancer (GC) treatment. Recent studies have shown lncRNAs play pivotal roles in regulating GC chemoresistance. Nanocarriers delivery of small interfering RNAs (siRNAs) to silence cancer-related genes has become a novel approach to cancer treatment research. However, finding target genes and developing nanosystems capable of selectively delivering siRNAs for disease treatment remains a challenge. In this study, a novel lncRNA TMEM44-AS1 that is related to 5-FU resistance is identified. TMEM44-AS1 has the ability to bind to and sponge miR-2355-5p, resulting in the upregulated PPP1R13L expression and P53 pathway inhibition. Next, a new nanocarrier called chitosan-gelatin-EGCG (CGE) is developed, which has a higher gene silencing efficiency than lipo2000, to aid in the delivery of a si-TMEM44-AS1 can efficiently silence TMEM44-AS1 expression to synergistically reverse 5-FU resistance in GC, leading to a markedly enhanced 5-FU therapeutic effect in a xenograft mouse model of GC. These findings indicate that TMEM44-AS1 may estimate 5-FU therapy outcome among GC cases, and that systemic si-TMEM44-AS1 delivery combined with 5-FU therapy is significant in the treatment of patients with recurrent GC.

Targeting BCAT1 Combined with α-Ketoglutarate Triggers Metabolic Synthetic Lethality in Glioblastoma.

Branched-chain amino acid transaminase 1 (BCAT1) is upregulated selectively in human isocitrate dehydrogenase (IDH) wildtype (WT) but not mutant glioblastoma multiforme (GBM) and promotes IDHWT GBM growth. Through a metabolic synthetic lethal screen, we report here that α-ketoglutarate (AKG) kills IDHWT GBM cells when BCAT1 protein is lost, which is reversed by reexpression of BCAT1 or supplementation with branched-chain α-ketoacids (BCKA), downstream metabolic products of BCAT1. In patient-derived IDHWT GBM tumors in vitro and in vivo, cotreatment of BCAT1 inhibitor gabapentin and AKG resulted in synthetic lethality. However, AKG failed to evoke a synthetic lethal effect with loss of BCAT2, BCKDHA, or GPT2 in IDHWT GBM cells. Mechanistically, loss of BCAT1 increased the NAD+/NADH ratio but impaired oxidative phosphorylation, mTORC1 activity, and nucleotide biosynthesis. These metabolic alterations were synergistically augmented by AKG treatment, thereby causing mitochondrial dysfunction and depletion of cellular building blocks, including ATP, nucleotides, and proteins. Partial restoration of ATP, nucleotides, proteins, and mTORC1 activity by BCKA supplementation prevented IDHWT GBM cell death conferred by the combination of BCAT1 loss and AKG. These findings define a targetable metabolic vulnerability in the most common subset of GBM that is currently incurable. SIGNIFICANCE: Metabolic synthetic lethal screening in IDHWT glioblastoma defines a vulnerability to ΑΚG following BCAT1 loss, uncovering a therapeutic strategy to improve glioblastoma treatment. See related commentary by Meurs and Nagrath, p. 2354.

Oral Huzhang granules for the treatment of acute gouty arthritis: protocol for a double-blind, randomized, controlled trial.

BACKGROUND: Acute gouty arthritis (GA) is the main clinical manifestation and the most common initial symptom of gout. The treatment of acute GA involves the use of colchicine, non-steroidal anti-inflammatory drugs, and corticosteroids. Because of the side effects of these drugs, their clinical applications are limited. The use of traditional Chinese medicine for the treatment of acute GA has unique advantages. The aim of this trial is to clarify the treatment efficacy, safety, and recurrence control efficacy of Huzhang granules (HZG) in patients with GA showing dampness-heat syndrome. METHODS/DESIGN: This double-blind, randomized, controlled trial was planned to be conducted between July 1, 2020, and December 31, 2022. A sample size of 267 participants (89 per group) with GA will be randomly assigned to three treatment groups in the ratio of 1:1:1: HZG, etoricoxib, and placebo groups. The study duration is 13 days, including a 1-day screening period, 5-day intervention period, and 1-week follow-up period. The primary outcome is analgesic effectiveness, assessed as pain in the worst-affected joint, which will be measured using the visual analog scale. Secondary outcomes include the patient's assessment of pain in the primary study joint, patient's global assessment of response to therapy, investigator's global assessment of response to therapy, investigator's assessment of tenderness and swelling of the study joint, and TCM syndromes. Furthermore, the number, nature, and severity of adverse events will be recorded. DISCUSSION: This study will provide evidence regarding the clinical efficacy and safety of Chinese medicine treatment for acute gouty arthritis. This study will provide noteworthy findings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04462666 . Registered on July 05, 2020 (first version).

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara.

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 µmol·L-1, respectively.

Physiological responses of black locust-rhizobia symbiosis to water stress.

The present study explores the interaction of water supply and rhizobia inoculation on CO2 and H2 O gas exchange characteristics, physiological and biochemical traits in seedlings of Robinia pseudoacacia L. originating from two provenances with contrasting climate and soil backgrounds: the Gansu Province (GS) in northwest China and the Dongbei region (DB) of northeast China. Rhizobia strains were isolated from the 50-years old Robinia forest sites grown in the coastal region of east China. Robinia seedlings with and without rhizobia inoculation were exposed to normal water supply, moderate drought, and rewatering treatments, respectively. After 2 weeks of drought treatment, photosynthetic and physiological traits (net photosynthetic rate, stomatal conductance, stable isotope signature of carbon, malondialdehyde and hydrogen peroxide content) of Robinia leaves were significantly altered, but after rewatering, a general recovery was observed. Rhizobia inoculation significantly increased the drought resistance of both Robinia provenances by promoting photosynthesis, increasing the foliar N content and reducing the accumulation of malondialdehyde and hydrogen peroxide. Among the two provenances, DB plants developed more nodules than GS plants, but GS plants were more drought-tolerant than DB plants, both inoculated or noninoculated, indicated by the foliar gas exchange parameters and biochemical traits studied. Our results also show that inoculation of rhizobia could significantly improve the drought resistance of Robinia in both provenances. The present study contributes to the scientific background for the selection of drought-resistant varieties of Robinia to ensure the success of future afforestation projects in degraded terrestrial ecosystems under global climate change.

[Evaluation of methodological and reporting quality of domestic clinical guidelines for hyperuricemia].

This study aims to evaluate the methodological and reporting quality of diagnosis and treatment guidelines for hyperuricemia as well as the expert consensuses and promote the understanding and application of the diagnosis and treatment guidelines for hyperuricemia. With "hyperuricemia" "guidelines" "consensus" "recommendations" as the key words in titles, the authors searched for the published clinical guidelines on hyperuricemia in Chinese against CNKI, Wanfang, VIP, Medlive and the official website of the industry association. The retrieval time limit was until May 31, 2021. The appraisal of guidelines for research and evaluation Ⅱ(AGREEⅡ) and the reporting items for practice guidelines in health care(RIGHT) were employed to evaluate the methodological quality and reporting quality of 14 guidelines/consensuses included. The average scores of the guidelines/consensuses were 80.85%(48.61%-98.61%) for the domain of scope and purpose, 34.52%(0-69.44%) for the domain of stakeholder involvement, 35.53%(6.25%-92.19%) for the domain of rigor of development, 55.85%(23.61%-86.11%) for the domain of clarity of presentation, 26.19%(0-76.04%) for the domain of applicability, and 21.42%(0-50.00%) for the domain of editorial independence. Nine guidelines/consensuses were of medium overall quality with grade B recommendation, and five guidelines/consensuses were of poor quality with grade C recommendation. The RIGHT classified the fourteen guidelines/consensuses into one of high reporting quality, three of medium reporting quality, and ten of low reporting quality. The results of this study indicate that the standardization and rigor of the methodological quality and the reporting quality of the clinical guidelines/consensuses for hyperuricemia in China remain to be strengthened.