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Background: Lipid metabolism disorders have become a major global public health issue. Due to the complexity of these diseases, additional research and drugs are needed. Oroxin A, the major component of Oroxylum indicum (L.) Kurz (Bignoniaceae), can improve the lipid profiles of diabetic and insulin-resistant (IR) rats. Because insulin resistance is strongly correlated with lipid metabolism, improving insulin resistance may also constitute an effective strategy for improving lipid metabolism. Thus, additional research on the efficacy and mechanism of oroxin An under non-IR conditions is needed. Methods: In this study, we established lipid metabolism disorder model rats by high-fat diet feeding and fatty HepG2 cell lines by treatment with oleic acid and evaluated the therapeutic effect and mechanism of oroxin A in vitro and in vivo through biochemical indicator analysis, pathological staining, immunoblotting, and immunofluorescence staining. Results: Oroxin A improved disordered lipid metabolism under non-IR conditions, improved the plasma and hepatic lipid profiles, and enhanced the lipid-lowering action of atorvastatin. Additionally, oroxin A reduced the total triglyceride (TG) levels by inhibiting sterol regulatory element-binding protein 1 (SREBP1) expression and reducing the expression of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FASN) in vivo and in vitro. Oroxin A also reduced the total cholesterol (TC) levels by inhibiting SREBP2 expression and reducing HMGCR expression in vivo and in vitro. In addition, oroxin A bound to low-density lipoprotein receptor (LDLR) and increased AMPK phosphorylation. Conclusions: Our results suggested that oroxin A may modulate the nuclear transcriptional activity of SREBPs by binding to LDLR proteins and increasing AMPK phosphorylation. Oroxin A may thus reduce lipid synthesis and could be used for the treatment and prevention of lipid metabolism disorders.

Metabolic-associated fatty liver disease (MAFLD) is a chronic liver disease characterized by the excessive accumulation of fat in hepatocytes. However, due to the complex pathogenesis of MAFLD, there are no officially approved drugs for treatment. Therefore, there is an urgent need to find safe and effective anti-MAFLD drugs. Recently, the relationship between the gut microbiota and MAFLD has been widely recognized, and treating MAFLD by regulating the gut microbiota may be a new therapeutic strategy. Natural products, especially plant natural products, have attracted much attention in the treatment of MAFLD due to their multiple targets and pathways and few side effects. Moreover, the structure and function of the gut microbiota can be influenced by exposure to plant natural products. However, the effects of plant natural products on MAFLD through targeting of the gut microbiota and the underlying mechanisms are poorly understood. Based on the above information and to address the potential therapeutic role of plant natural products in MAFLD, we systematically summarize the effects and mechanisms of action of plant natural products in the prevention and treatment of MAFLD through targeting of the gut microbiota. This narrative review provides feasible ideas for further exploration of safer and more effective natural drugs for the prevention and treatment of MAFLD.

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a common chronic metabolic disease that seriously threatens human health. The pharmacological activity of unsaturated fatty acid-rich vegetable oil interventions in the treatment of MAFLD has been demonstrated. This study evaluated the pharmacological activity of Polygala tenuifolia Willd, which contains high levels of 2-acetyl-1,3-diacyl-sn-glycerols (sn-2-acTAGs).Methods: In this study, a mouse model was established by feeding a high-fat diet (HFD, 31% lard oil diet), and the treatment group was fed a P. tenuifolia seed oil (PWSO) treatment diet (17% lard oil and 14% PWSO diet). The pharmacological activity and mechanism of PWSO were investigated by total cho-lesterol (TC) measurement, triglyceride (TG) measurement and histopathological observation, and the sterol regulatory element-binding protein-1 (SREBP1), SREBP2 and NF-κB signaling pathways were evaluated by immunofluorescence and Western blot analyses.Results: PWSO attenuated the increases in plasma TC and TG levels. Furthermore, PWSO reduced the hepatic levels of TC and TG, ameliorating hepatic lipid accumulation. PWSO treatment effectively improves the level of hepatitic inflammation, such as reducing IL-6 levels and TNF-α level.Discussion: PWSO treatment inactivated SREBP1 and SREBP2, which are involved in lipogenesis, to attenuate hepatic lipid accumulation and mitigate the inflammatory response induced via the NF-κB signaling pathway. This study demonstrated that PWSO can be used as a relatively potent dietary supplement to inhibit the occurrence and development of MAFLD.

Obesity is strongly associated with the occurrence and development of many types of cancers. Patients with obesity and cancer present with features of a disordered gut microbiota and metabolism, which may inhibit the physiological immune response to tumors and possibly damage immune cells in the tumor microenvironment. In recent years, bariatric surgery has become increasingly common and is recognized as an effective strategy for long-term weight loss; furthermore, bariatric surgery can induce favorable changes in the gut microbiota. Some studies have found that microbial metabolites, such as short-chain fatty acids (SCFAs), inosine bile acids and spermidine, play an important role in anticancer immunity. In this review, we describe the changes in microbial metabolites initiated by bariatric surgery and discuss the effects of these metabolites on anticancer immunity. This review attempts to clarify the relationship between alterations in microbial metabolites due to bariatric surgery and the effectiveness of cancer treatment. Furthermore, this review seeks to provide strategies for the development of microbial metabolites mimicking the benefits of bariatric surgery with the aim of improving therapeutic outcomes in cancer patients who have not received bariatric surgery.

Men with erectile dysfunction (ED) are considered to be at risk from stroke events. Conversely, post-stroke patients are also at high risk of ED, whereas a quantitative result from all the relevant studies has not been previously addressed. Therefore, we have performed a comprehensive review and meta-analysis on this issue. This study was registered on PROSPERO (ID No. CRD42021226618). Twenty studies with a total of 3,382 stroke events were included, of which six studies were included for quantitative analysis, and the remaining 14 studies were calculated for the ratio of ED. Synthetic results from four eligible studies providing the ED cases showed that stroke patients were associated with a significantly higher risk of ED than the general population [pooled relative risk (RR) = 3.32, 95% confidence interval (CI): 1.25–8.82, P = 0.016]. Men with stroke were also found to be associated with a significant decline in International Index of Erectile Function −5 (IIEF-5) score as compared with the healthy controls [three studies, standard mean differences (SMD) = −1.8, 95% CI: −2.94 to −0.67, P = 0.002]. The prevalence of ED in post-stroke patients among 14 studies ranged from 32.1 to 77.8%, which was dramatically higher than that of the general population. The result of the GRADE-pro revealed that the quality of the evidence in this study was moderate. The present study has confirmed the high prevalence of ED in men with stroke. ED in stroke patients is a result of both neurological and psychological factors. Rehabilitative interventions rather than phosphodiesterase-5 (PDE-5) inhibitors are recommended to improve the erectile function for those survivors with ED.

Substantial heterogeneity exists within cervical cancer that is generally infected by human papillomavirus (HPV). However, the most common histological subtype of cervical cancer, cervical squamous cell carcinoma (CSCC), is poorly characterized regarding the association between its heterogeneity and HPV oncoprotein expression. We filtered out 138 CSCC samples with infection of HPV16 only as the first step; then we compressed HPV16 E6/E7 expression as HPVpca and correlated HPVpca with the immunological profiling of CSCC based on supervised clustering to discover subtypes and to characterize the differences between subgroups in terms of the HPVpca level, pathway activity, epigenetic dysregulation, somatic mutation frequencies, and likelihood of responding to chemo/immunotherapies. Supervised clustering of immune signatures revealed two HPV16 subtypes (namely, HPV16-IMM and HPV16-KRT) that correlated with HPVpca and clinical outcomes. HPV16-KRT is characterized by elevated expression of genes in keratinization, biological oxidation, and Wnt signaling, whereas HPV16-IMM has a strong immune response and mesenchymal features. HPV16-IMM exhibited much more epigenetic silencing and significant mutation at FBXW7, while MUC4 and PIK3CA were mutated frequently for HPV16-KRT. We also imputed that HPV16-IMM is much more sensitive to chemo/immunotherapy than is HPV16-KRT. Our characterization tightly links the expression of HPV16 E6/E7 with biological and clinical outcomes of CSCC, providing valuable molecular-level information that points to decoding heterogeneity. Together, these results shed light on stratifications of CSCC infected by HPV16 and shall help to guide personalized management and treatment of patients.

The status of lymph node (LN) metastases plays a decisive role in the selection of surgical procedures and post-operative treatment. Several histopathologic features, known as predictors of LN metastasis, are commonly available post-operatively. Medical imaging improved pre-operative diagnosis, but the results are not fully satisfactory due to substantial false positives. Thus, a reliable and robust method for pre-operative assessment of LN status is urgently required. We developed a prediction model in a training set from the TCGA-BLCA cohort including 196 bladder urothelial carcinoma samples with confirmed LN metastasis status. Least absolute shrinkage and selection operator (LASSO) regression was harnessed for dimension reduction, feature selection, and LNM signature building. Multivariable logistic regression was used to develop the prognostic model, incorporating the LNM signature, and a genomic mutation of MLL2, and was presented with a LNM nomogram. The performance of the nomogram was assessed with respect to its calibration, discrimination, and clinical usefulness. Internal validation was evaluated by the testing set from the TCGA cohort and independent validation was assessed by two independent cohorts. The LNM signature, which consisted of 48 selected features, was significantly associated with LN status (p < 0.005 for both the training and testing sets of the TCGA cohort). Predictors contained in the individualized prediction nomogram included the LNM signature and MLL2 mutation status. The model demonstrated good discrimination, with an area under the curve (AUC) of 98.7% (85.3% for testing set) and good calibration with p = 0.973 (0.485 for testing set) in the Hosmer-Lemeshow goodness of fit test. Decision curve analysis demonstrated that the LNM nomogram was clinically useful. This study presents a pre-operative nomogram incorporating a LNM signature and a genomic mutation, which can be conveniently utilized to facilitate pre-operative individualized prediction of LN metastasis in patients with bladder urothelial carcinoma.

A free-radical-promoted aryl/heteroaryl C-H silylation using hydrosilane was developed. This cross-dehydrogenative silylation enables both electron-rich and electron-poor aromatics to afford the desired arylsilanes in unique selectivity. A "para-selectivity" was observed by examination of over 54 examples. This exceptional orientation is quite different from that in Friedel-Crafts C-H silylation or transition-metal-catalyzed dehydrogenative silylation. [ABSTRACT FROM AUTHOR]

A C-C formation of an electron-rich N-heterocycle with fluorinated alcohol is developed. Through this radical-triggered cross-dehydrogenative coupling strategy, a wide range of useful building blocks such as C3 hydroxyfluoroalkylated indoles and pyrroles can be site-specifically synthesized. Mechanistic studies indicate a single-electron-transfer initiated radical cycle would be involved. [ABSTRACT FROM AUTHOR]

A free-radical mediated highly ordered radical addition/cyclization/(sp³)C-C(sp³) formation domino reaction is developed. Three new C-C bonds are formed one by one in a mixed system. Furthermore, it represents the first example of cascade C-C bond formation via selective functionalization of α-hydroxyl-C(sp³)-H in fluorinated alcohols. [ABSTRACT FROM AUTHOR]