Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance， while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine （TCM） has a long history in the prevention and management of this condition， demonstrating eight distinct advantages， including systematic theoretical foundation， diversified therapeutic approaches， definite therapeutic efficacy， high safety profile， good patient compliance， comprehensive intervention strategies， emphasis on prevention， and stepwise treatment protocols. Additionally， TCM is characterized by six distinctive features： the use of natural medicinal substances， non-invasive external therapies， integration of medicinal dietetics， simple exercise regimens， precise syndrome differentiation， and diverse dosage forms. By combining internal and external treatments， TCM facilitates individualized regimen adjustment and holistic regulation， demonstrating remarkable effects in improving obesity-related metabolic indicators， regulating constitutional imbalance， and promoting healthy behaviors. However， challenges remain， such as inconsistent operational standards， insufficient high-quality clinical evidence， and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment， conducting multicenter randomized controlled trials， and fostering interdisciplinary integration， so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.

Objective To investigate the role and regulatory mechanism of LINC00657 in the progression of cervical cancer. Methods Bioinformatics analysis predicted potential binding sites between LINC00657 and miR-30a-5p and between miR-30a-5p and Skp2. These sites were verified by using RNA immunoprecipitation and dual-luciferase reporter experiments. LINC00657, miR-30a-5p, and Skp2 mRNA expression levels in cervical cancer tissues and cell lines were assessed by utilizing RT-qPCR. Western blot analysis was employed to examine the protein levels of Skp2 in cells and subcutaneous xenograft tumor models in nude mice. Immunohistochemistry was applied to analyze Skp2 expression in animal tissues. The cellular processes of cervical cancer cell lines were evaluated through CCK-8, scratch, and Transwell assays. Results LINC00657 and Skp2 presented binding sites for miR-30a-5p. In cervical cancer, LINC00657 and Skp2 showed high expression levels (P<0.05), whereas miR-30a-5p displayed low expression (P<0.05). Functional experiments demonstrated that linc00657 upregulates Skp2 expression, a process that is dependent on its sequestration of miR-30a-5p. Conclusion LINC00657 promoted the malignant progression of cervical cancer by upregulating Skp2 expression through specifically sequestering miR-30a-5p, thereby relieving its inhibitory effect on the target gene Skp2.

ObjectiveTo investigate the mechanism through which miR‑21 improves chronic renal fibrosis in mice via targeted modulation of the phosphatase and tensin homolog （PTEN）/protein kinase B （AKT）/mammalian target of rapamycin （mTOR） pathway. MethodsThirty‑two chronic kidney disease model mice were randomly divided into four groups （n=8 each group）： model group， miR‑21 overexpression group， miR‑21 inhibition group， and miR‑21 inhibition + MK‑2206 group. Eight healthy mice were included as the control group. The miR‑21 overexpression， miR‑21 inhibition， and miR‑21 inhibition + MK‑2206 groups received tail‑vein injections of lentivirus （50 μL， 1×10⁸ TU per mouse） once weekly for three weeks. The control and model groups were injected with an equal volume of empty vector （LV‑NC）. The miR‑21 inhibition + MK‑2206 group additionally received gavage of the AKT/mTOR pathway inhibitor MK‑2206 （480 mg/kg） once weekly for three weeks. The expressions of miR‑21， 24 h urinary protein， serum creatinine （Scr）， blood urea nitrogen （BUN）， and renal tissue levels of collagen Ⅰ， collagen Ⅲ， α‑smooth muscle actin （α‑SMA）， and PTEN protein， as well as p‑AKT/AKT and p‑mTOR/mTOR ratios， were compared among groups. HE staining was used to observe pathological changes in renal tissue， and Masson staining was used to observe the degree of renal fibrosis. A dual‑luciferase assay was performed to verify the targeting relationship between miR‑21 and PTEN. ResultsCompared with the model group， miR‑21 expression in renal tissue increased in the miR‑21 overexpression group （P<0.05） and decreased in the miR‑21 inhibition group （P<0.05）. Compared with the model group， the miR‑21 overexpression group showed increased 24 h urinary protein， Scr， BUN， and renal tissue expression of collagen Ⅰ， collagen Ⅲ， and α‑SMA （all P<0.05）， while these indicators decreased in the miR‑21 inhibition group （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group exhibited lower 24‑h urinary protein， Scr， BUN， and renal tissue expression of Collagen Ⅰ， Collagen Ⅲ， and α‑SMA （all P<0.05）. Compared with the model group， the miR‑21 overexpression group showed decreased PTEN protein expression （P<0.05） and increased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， while the miR‑21 inhibition group showed increased PTEN expression （P<0.05） and decreased p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）. Compared with the miR‑21 inhibition group， the miR‑21 inhibition + MK‑2206 group had lower p‑AKT/AKT and p‑mTOR/mTOR ratios （P<0.05）， with no significant difference in PTEN protein expression. HE and Masson staining showed normal kidney structure and almost no fibrosis in the control group. The model group exhibited glomerular enlargement， capillary loop adhesion， and focal fibrosis. The miR-21 overexpression group showed severe destruction of glomerular structure， accompanied by extensive fibrosis and renal tubular atrophy. The pathological changes and degree of fibrosis were alleviated in the miR-21 inhibition group. The miR-21 inhibition + MK-2206 group showed only mild pathological changes and mild fibrosis， with the interstitium being largely normal. Compared with PTEN-WT + NC mimics 1， the relative luciferase activity in the PTEN-WT + miR-21 mimics group decreased （P<0.001）. There was no statistically significant difference in relative luciferase activity between PTEN-WT + NC mimics group and PTEN-MUT + miR-21 mimics group. ConclusionmiR‑21 may improve renal function indicators and alleviate renal fibrosis in chronic kidney disease mice via targeted modulation of PTEN and subsequently inhibiting the AKT/mTOR pathway.

Background Pyrethroid pesticides (PYRs) can cross the placental barrier to cause intrauterine fetal exposure, which may lead to developmental immunotoxicity (DIT). However, the specific effect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. Objective To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. Methods A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age. Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites, including 3-phenoxybenzoic acid (3PBA), 4-fluoro-3-phenoxybenzoic acid (4F3PBA), and cis-3-(2,2-dichlorovinyl)-2,2- dimethylcyclopropane carboxylic acid (cis-DBCA), in the urine of pregnant women during the first trimester (gestational weeks 6-12), the second trimester (gestational weeks 21-24), and the third trimester (gestational weeks 33-36). Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry. Exposure levels of PYRs metabolites in each trimester were divided into low, moderate, and high exposure groups based on the 25th (P₂₅) and 75th (P₇₅) percentiles. Meanwhile, participants were classified as having repeated high or low exposure if their metabolite levels were > P₇₅ or <P₂₅ in at least two trimesters, respectively, while all others were categorized as having repeated moderate exposure. Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell (WBC) and lymphocyte counts in children aged 1 year. Results A total of 336 mother-child pairs were included in this study. For the pregnant women, the total detection rates of maternal urinary 3PBA, 4F3PBA, and cis-DBCA across the three trimesters of pregnancy were 80.5%, 100.0%, and 81.3%, respectively; and median creatinine-corrected concentrations were 0.24, 0.36, and 0.42 μg·g⁻¹, respectively. In children aged 1 year, the mean WBC and lymphocyte counts in peripheral blood were (8.9±2.0)×10⁹·L⁻¹ and (5.7±1.6)×10⁹·L⁻¹, respectively. The results of the generalized linear model analysis indicated that compared to the low exposure group, the high cis-DBCA exposure group during the third trimester of pregnancy had significantly lower peripheral blood WBC count (β=−0.87, 95%CI: −1.51, −0.23) and lymphocyte count (β=−0.64, 95%CI: −1.15, −0.13); and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count (β=−1.34, 95%CI: −2.34, −0.34) and lymphocyte count (β=−0.80, 95%CI: −1.60, −0.01) than the repeated low exposure group. Similarly, the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count (β=−0.83, 95%CI: −1.59, −0.07) than the repeated low exposure group. Conclusion High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year, and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring. The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during pregnancy.

ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.

The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

In recent years, there has been a growing interest in the research on NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome inhibitors in the treatment of inflammatory diseases. The NLRP3 inflammasome is integral to the innate immune response, and its abnormal activation can lead to the release of pro-inflammatory cytokine, consequently facilitating the progression of various pathological conditions. Therefore, investigating the pharmacological inhibition pathway of the NLRP3 inflammasome represents a promising strategy for the treatment of inflammation-related diseases. Currently, the Food and Drug Administration(FDA) has not approved drugs targeting the NLRP3 inflammasome for clinical use due to concerns regarding liver toxicity and gastrointestinal side effects associated with chemical small molecule inhibitors in clinical trials. Natural small molecule compounds such as polyphenols, flavonoids, and alkaloids are ubiquitously found in animals, plants, and other natural substances exhibiting pharmacological activities. Their abundant sources, intricate and diverse structures, high biocompatibility, minimal adverse reactions, and superior biochemical potency in comparison to synthetic compounds have attracted the attention of extensive scholars. Currently, certain natural small molecule compounds have been demonstrated to impede the activation of the NLRP3 inflammasome via various action mechanisms, so they are viewed as the innovative, feasible, and minimally toxic therapeutic agents for inhibiting NLRP3 inflammasome activation in the treatment of both acute and chronic inflammatory diseases. Hence, this study systematically examined the effects and potential mechanisms of natural small molecule compounds derived from traditional Chinese medicine on the activation of NLRP3 inflammasomes at their initiation, assembly, and activation stages. The objection is to furnish theoretical support and practical guidance for the effective clinical application of these natural small molecule inhibitors.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Inflammasomes/metabolism* ; Inflammation/drug therapy* ; Anti-Inflammatory Agents/therapeutic use* ; Humans ; Animals ; Disease Models, Animal ; Biological Products/therapeutic use* ; Drug Discovery ; Medicine, Chinese Traditional/methods*

Hepatocellular carcinoma(HCC), the third leading cause of cancer-related death worldwide, is characterized by high mortality and recurrence rates. Common treatments include hepatectomy, liver transplantation, ablation therapy, interventional therapy, radiotherapy, systemic therapy, and traditional Chinese medicine(TCM). While exhibiting specific advantages, these approaches are associated with varying degrees of adverse effects. To alleviate patients' suffering and burdens, it is crucial to explore additional treatments and elucidate the pathogenesis of HCC, laying a foundation for the development of new TCM-based drugs. With emerging research on gut microbiota, it has been revealed that microbiota plays a vital role in the development of HCC by influencing intestinal barrier function, microbial metabolites, and immune regulation. TCM, with its multi-component, multi-target, and multi-pathway characteristics, has been increasingly recognized as a vital therapeutic treatment for HCC, particularly in patients at intermediate or advanced stages, by prolonging survival and improving quality of life. Recent global studies demonstrate that TCM exerts anti-HCC effects by modulating gut microbiota, restoring intestinal barrier function, regulating microbial composition and its metabolites, suppressing inflammation, and enhancing immune responses, thereby inhibiting the malignant phenotype of HCC. This review aims to elucidate the mechanisms by which gut microbiota contributes to the development and progression of HCC and highlight the regulatory effects of TCM, addressing the current gap in systematic understanding of the "TCM-gut microbiota-HCC" axis. The findings provide theoretical support for integrating TCM with western medicine in HCC treatment and promote the transition from basic research to precision clinical therapy through microbiota-targeted drug development and TCM-based interventions.
Humans ; Gastrointestinal Microbiome/drug effects* ; Carcinoma, Hepatocellular/microbiology* ; Liver Neoplasms/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Medicine, Chinese Traditional

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

OBJECTIVE: Huachansu injection (HCSI), a promising anti-cancer Chinese medicine injection, has been reported to have the potential for reducing the toxicity of chemotherapy and improving the quality of life for colorectal cancer (CRC) patients. The objective of this study is to explore the synergistic and detoxifying effects of HCSI when used in combination with irinotecan (CPT-11). METHODS: To investigate the effect of HCSI on anti-CRC efficacy and intestinal toxicity of CPT-11, we measured changes in the biological behavior of LoVo cells in vitro, and anti-tumor effects in LoVo cell xenograft nude mice models in vivo. Meanwhile, the effect of HCSI on intestinal toxicity and the uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) expression was investigated in the CPT-11-induced colitis mouse model. Subsequently, we measured the effect of HCSI and its 13 constituent bufadienolides on the expression of UGT1A1 and organic anion transporting polypeptides 1B3 (OATP1B3) in HepG2 cells. RESULTS: The combination index (CI) results showed that the combination of HCSI and CPT-11 exhibited a synergistic effect (CI < 1), which significantly suppressing the LoVo cell migration, enhancing G2/M and S phase arrest, and inhibiting tumor growth in vivo. Additionally, the damage to intestinal tissues was attenuated by HCSI in CPT-11-induced colitis model, while the increased expression of UGT1A1 in HepG2 cells and in mouse was observed. CONCLUSION The co-therapy with HCSI alleviated the intestinal toxicity induced by CPT-11 and exerted an enhanced anti-CRC effect. The detoxifying mechanism may be related to the increased expression of UGT1A1 and OATP1B3 by HCSI and its bufadienolides components. The findings of this study may serve as a theoretical insights and strategies to improve CRC patient outcomes. Please cite this article as: Jiang B, Meng ZY, Hu YJ, Chen JJ, Zong L, Xu LY, Zhang XQ, Zhang JX, Han YL. Huachansu injection enhances anti-colorectal cancer efficacy of irinotecan and alleviates its induced intestinal toxicity through upregulating UGT1A1-OATP1B3 expression in vitro and in vivo. J Integr Med. 2025; 23(5):576-590.
Irinotecan/therapeutic use* ; Animals ; Glucuronosyltransferase/genetics* ; Humans ; Colorectal Neoplasms/metabolism* ; Drugs, Chinese Herbal/therapeutic use* ; Mice, Nude ; Mice ; Up-Regulation/drug effects* ; Male ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Hep G2 Cells ; Cell Line, Tumor ; Intestines/drug effects* ; Amphibian Venoms