1.Effect and mechanism of Wnt5a knockdown on the efficacy of M1 bone marrow-derived macrophage in treatment of liver cirrhosis
Feifei XING ; Danyang WANG ; Xinrui ZHENG ; Yannan XU ; Shihao ZHANG ; Junyi ZHAN ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(3):618-628
ObjectiveTo observe the effect of M1 bone marrow-derived macrophages (M1-BMDM) with Wnt5a knockdown on liver fibrosis and regeneration in a rat model of liver cirrhosis, and to investigate its gain-of-function effect compared with unmodified M1-BMDM. MethodsPrimary bone marrow-derived macrophages were isolated from rats and were polarized to M1 phenotype to construct M1-BMDMWnt5a-KD cells. A rat model of liver cirrhosis induced by CCl4/2-AAF was established, and at the end of week 8, rats were randomly divided into model group, M1-BMDM group, M1-BMDM Wnt5a-knockdown empty vector group (M1-BMDMKD-EV group), and M1-BMDM Wnt5a-knockdown group (M1-BMDMWnt5a-KD group), with 6 rats in each group. On the first day of week 9, the rats in each group were given a single injection of the corresponding cells via the caudal vein, along with an intraperitoneal injection of a CCR2 inhibitor. Six rats without any treatment were used as normal control group. Samples were collected at the end of week 12 to assess liver histopathology, serum liver function parameters, hepatic stellate cell activation, and the expression levels of mature hepatocyte markers. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the model group, all cell treatment groups had significant alleviation of liver inflammatory response and significant reductions in the activities of alanine aminotransferase and aspartate aminotransferase (AST) in serum (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly lower serum level of AST than the M1-BMDM group (P<0.05). The semi-quantitative analysis based on immunohistochemical staining showed that compared with the model group, all cell treatment groups had a significant reduction in the percentage of CD68-positive area (all P<0.05), and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had a significant reduction in the percentage of CD68-positive area and a significant increase in the percentage of CD163-positive area (both P<0.05). Compared with the model group, all cell treatment groups had significant reductions in the mRNA expression levels of CD68 and tumor necrosis factor-α (all P<0.05) and the protein expression level of CD68 (all P<0.01); compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant increases in the protein and mRNA expression levels of CD163 (both P<0.05), significant reductions in the protein and mRNA expression levels of CD68 (both P<0.05), and a significant reduction in the protein expression level of tumor necrosis factor-α (P<0.01). Sirius Red collagen staining and alpha-smooth muscle actin (α-SMA) immunohistochemical staining showed that compared with the model group, all cell treatment groups had significant alleviation of liver collagen deposition and α-SMA-positive area, with the most significant changes in the M1-BMDMWnt5a-KD group, and compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significantly smaller Sirius Red-positive area and α-SMA-positive area and a significantly lower content of hydroxyproline in liver tissue (all P<0.05). Compared with the M1-BMDMKD-EV group, the M1-BMDMWnt5a-KD group had significant reductions in the protein and mRNA expression levels of α-SMA and the mRNA expression level of COL-I and TGF-β (all P<0.05). Compared with the model group, all cell treatment groups had a significant increase in the protein expression level of HNF-4α in liver tissue (all P<0.05), and the M1-BMDMWnt5a-KD group had significantly higher protein and mRNA expression levels of HNF-4α and hepatocyte specific antigen than the M1-BMDMKD-EV group (both P<0.05). The M1-BMDMWnt5a-KD group had a significantly higher serum level of albumin than the M1-BMDMKD-EV group (P<0.01). Immunofluorescence co-staining showed that compared with the model group, all cell treatment groups had a significant increase in the number of cells stained positive for HNF and HNF-4α and Ki67 (all P<0.01), and the M1-BMDMWnt5a-KD group had a significantly higher number of such cells than the M1-BMDMKD-EV group (P<0.05). ConclusionInhibition of Wnt5a expression enhances the therapeutic effect of M1-BMDM on rats with liver cirrhosis induced by CCl4/2-AAF, which provides new ideas for enhancing the anti-cirrhotic effect of M1-BMDM through genetic modification.
2.Wumeiwan Promotes M1 Polarization of Tumor-associated Macrophages to Treat Metastatic Colorectal Cancer
Nianzhi CHEN ; Shiyun TANG ; Yuanyuan FENG ; Yan WANG ; Ningning LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):92-100
ObjectiveTo explore the effects of Wumeiwan on liver metastasis and lung metastasis of colorectal cancer and its potential mechanism. MethodsFirstly, mice were randomized into control, low-dose (20 g·kg-1) Wumeiwan, high-dose (40 g·kg-1) Wumeiwan, and paclitaxel (10 mg·kg-1) groups. Secondly, liver metastasis and lung metastasis models of colorectal cancer were established in mice. After 4 weeks of intervention, the body weight of each mouse was recorded, and the lung weight, liver weight, and survival time of mice with metastatic colorectal cancer were determined. Hematoxylin-eosin (HE) staining was employed to detect the effects of Wumeiwan on liver metastasis and lung metastasis. Real-time PCR was employed to determine the mRNA levels of M1 and M2 macrophage markers in the liver tissue. Finally, the content of M1 macrophage markers CD80 and CD86 in the liver tissue was measured by flow cytometry. ResultsCompared with the control group, Wumeiwan and paclitaxel reduced the body weight (P<0.01) and liver weight (P<0.01) and prolonged the survival of the mouse model of liver metastasis of colorectal cancer (P<0.01). In the mouse model of lung metastasis of colorectal cancer, Wumeiwan and paclitaxel also reduced the body weight (P<0.01) and lung weight (P<0.01) and extended the survival time (P<0.01). Histopathological results showed that compared with the control group, Wumeiwan inhibited the liver and lung metastases of colorectal cancer. Real-time PCR results showed that compared with the control group, Wumeiwan upregulated the mRNA levels of M1 macrophage markers IL-1β, IL-6, tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), and prostaglandin-endoperoxide synthase 2 (PTGS2) in the liver and lung tissue of mice with liver metastasis and lung metastasis of colorectal cancer (P<0.01). Meanwhile, Wumeiwan downregulated the mRNA levels of M2 macrophage markers Arg1, CD163, and CD206 (P<0.01). Meanwhile, the flow cytometry results showed that compared with the control group, Wumeiwan increased the content of CD86 and CD80 (P<0.01). In addition, immunohistochemical results showed that Wumeiwan promoted the expression of CD86 and inhibited the expression of CD206 in the liver and lung tissue of mice with liver metastasis and lung metastasis. ConclusionWumeiwan can inhibit the liver metastasis and lung metastasis of colorectal cancer by promoting the M1 polarization of macrophages in the liver and lung of the model mice.
3.Effect of Jianpi Qinghua Granules on Blood Glucose Fluctuations and Skeletal Muscle Mass and Function in Newly Diagnosed Overweight/Obese Type 2 Diabetes Patients with Qi-Yin Deficiency Syndrome
Yuan CHEN ; Qiuyue GUO ; Yanyan XIAO ; Hao LU ; Chi CHEN ; Junfei XU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(11):218-224
ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus (T2DM) and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function, while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized, double-blind, placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine (TCM) group (54 cases) or the control group (56 cases). Patients in the TCM group received Jianpi Qinghua Granules, while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention, blood glucose fluctuations were assessed using the following parameters: time in the target blood glucose range (TIR), mean daily blood glucose (MBG), standard deviation of mean daily blood glucose (SDBG), mean amplitude of glycemic excursions (MAGE), coefficient of variation of blood glucose (CV), glycated hemoglobin (HbA1c) achievement rate, fasting plasma glucose (FPG), and 2 hour postprandial glucose (2 hPG). Skeletal muscle mass was measured by dual-energy X-ray absorptiometry (DXA), while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally, pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention, ensuring comparability. After treatment, compared to the control group, the TCM group showed a significant increase in TIR (P<0.01). While the SDBG and CV decreased, and MBG and MAGE increased in the TCM group, these differences were not statistically significant. Notably, the TCM group exhibited significant reductions in 2 hPG (P<0.01) and HbA1c (P<0.05), though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group (χ2=45.498, P<0.01). In terms of skeletal muscle mass and function, the TCM group demonstrated a significant increase in handgrip strength (P<0.01) and a significant reduction in the 5-time sit-to-stand duration (P<0.05). However, although body fat percentage increased, leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat, these changes were not statistically significant. For pancreatic islet function, the TCM group showed significant reductions in fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) (P<0.01). Additionally, the TCM syndrome score in the TCM group was significantly reduced (P<0.01). ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function, improving pancreatic islet function, and ameliorating related TCM syndromes.
4.Jingmaiyan Granules Combined with External Application of Jinhuang Ointment in Treatment of Acute Stage Blood Heat Stasis Type Superficial Thrombophlebitis of Lower Extremities: A Randomized, Double-blind, Placebo-controlled Clinical Trial
Qiaoyilan LIANG ; Hong CHEN ; Weijing FAN ; Hongshuo SHI ; Fangfang WU ; Guobin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):196-202
ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules (composed of Lonicerae Japonicae Flos, Sedi Herba, Paeoniae Radix Rubra, Moutan Cortex, Rhei Radix et Rhizoma Praeparata, and Glycyrrhizae Radix et Rhizoma) combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis (ST) of lower extremities, and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups(62 cases in each group). The control group received external application of Jinhuang ointment and oral placebo treatment, while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores, therapeutic efficacy of traditional Chinese medicine (TCM) syndrome, pain visual analog scale (VAS) scores, hemorheological indices [including whole blood high-shear, medium-shear, and low-shear viscosity, as well as plasma viscosity (PV)], and inflammatory factors [C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α)] were compared before and after treatment. ResultsAfter 2 weeks of treatment, the total effective rate in the observation group (98.3%, 60/62) was significantly higher than that in the control group (83.8%, 52/62), with a statistically significant difference (Z=3.512 1, P<0.05). Compared with pre-treatment scores, the scores for skin color, skin temperature, swelling, pain, and cord or nodules were significantly reduced in both groups (P<0.05), with more pronounced improvement in the observation group (P<0.05). Additionally, compared with pre-treatment levels, the whole blood viscosity (low-, medium-, and high-shear) significantly improved in both groups after treatment (P<0.05), with more marked improvement in the observation group (P<0.05). Furthermore, the plasma viscosity, CRP, IL-6, and TNF-α levels were significantly reduced in both groups after treatment (P<0.05), with more pronounced improvement observed in the observation group (P<0.05). ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms, hemorheological abnormalities, and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.
5.Advances in Diabetic Peripheral Neuropathy Treatment by Traditional Chinese Medicine Based on Cellular Senescence: A Review
Qixian MA ; Shiyu HAN ; Hui HUANG ; Jing TIAN ; Xu HAN ; Qingguang CHEN ; Hao LU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(5):322-330
Diabetic Peripheral Neuropathy (DPN) is one of the most common and harmful complications of type 2 diabetes. DPN's pathogenesis include high blood sugar-induced oxidative stress, inflammation, and mitochondrial dysfunction. These factors are combined to damage nerve fibers, leading to sensory issues, pain, and numbness. Through a coordinated effect, these factors trigger nerve fiber damage and lead to sensory abnormalities, pain and numbness in limbs, and other symptoms, seriously restricting patients' activities of daily living and mobility. Recent research highlights that cellular senescence plays a critical role in DPN. Cellular senescence is manifested by the loss of cell proliferation ability, and further aggravates nerve damage via oxidative stress, mitochondrial dysfunction, autophagy impairment, inflammatory reaction, and other mechanisms, accelerating DPN occurrence and progression. In terms of medical treatment, current methods focus on blood sugar control, pain relief medicine, and microcirculation improvement, while no therapy has been developed based on cellular senescence. In contrast, traditional Chinese medicine (TCM) shows a unique advantage in DPN prevention and treatment via cellular senescence modulation. TCM emphasizes a holistic approach, as well as syndrome differentiation and treatment, effective in anti-aging and nerve damage repair. Recent studies show that TCM active ingredients, including puerarin, ginsenosides, and berberine, can reduce inflammation, oxidative stress, and apoptosis via signaling pathway regulation, thereby slowing cellular senescence to alleviate nerve damage. Furthermore, TCM compounds such as Buyang Huanwutang, Taohong Siwutang, and Huangqi Guizhi Wuwutang exert synergistic effects on cellular senescence-related pathways to improve nerve health and reduce DPN clinical symptoms. Therefore, this paper reviews the literature related to the interaction between cellular senescence and DPN from the perspective of cellular senescence, summarizing the mechanism of DPN and TCM intervention strategies.
6.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.
7.Efficacy and safety of sequential or combined therapy with tenofovir alafenamide fumarate in entecavir-treated patients with low-level viremia
Yijing ZHANG ; Lingying HUANG ; Bowu CHEN ; Wanchun ZHU ; Man LI ; Jie SHEN ; Yueqiu GAO
Journal of Clinical Hepatology 2026;42(1):66-73
ObjectiveTo investigate the efficacy of sequential tenofovir alafenamide fumarate (TAF) therapy versus the regimen of entecavir (ETV) combined with TAF in chronic hepatitis B (CHB) patients experiencing low-level viremia (LLV) after ETV therapy, as well as their impact on virologic response, liver and renal function, and blood lipid levels. MethodsA total of 217 CHB patients with LLV after ETV treatment who were admitted to Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from May 2020 to December 2023 were enrolled, and according to the treatment regimen, they were divided into TAF group (180 patients receiving sequential TAF therapy) and combined group (37 patients receiving ETV+TAF therapy). The propensity score matching (PSM) method was used to match the patients at a ratio of 1∶1, and finally 37 patients were included in each group to balance the baseline confounding factors. The two groups were compared in terms of hepatitis B virus DNA (HBV DNA) clearance rate, hepatitis B envelope antigen (HBeAg) clearance rate, liver and renal function parameters (liver stiffness measurement [LSM], platelet count [PLT], aspartate aminotransferase [AST], alanine aminotransferase [ALT], and creatinine [Cr]), blood lipid levels (total cholesterol [TC], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]), and the incidence rate of adverse reactions. The independent samples t-test was used for comparison of normally distributed continuous data between two groups, and the paired t-test was used for comparison within each group; the chi-square test was used for comparison of categorical data between groups. ResultsAfter 48 weeks of treatment, compared with the TAF group, the combined group had significantly higher HBV DNA clearance rate (86.49% vs 59.46%, χ²=6.852, P=0.009) and HBeAg clearance rate (59.46% vs 35.14%, χ²=4.391, P=0.036). After treatment, compared with the TAF group, the combined group had significantly lower levels of LSM (7.01±1.50 kPa vs 7.90±1.68 kPa, t=2.404, P=0.019), AST (18.02±2.28 U/L vs 21.12±2.85 U/L, t=5.166, P<0.001), and ALT (19.85±3.86 U/L vs 22.00±3.90 U/L, t=2.383, P=0.020) and significantly higher levels of PLT [(218.35±42.60)×109/L vs (192.82±44.13)×109/L, t=2.532, P=0.014] and Cr (70.92±6.54 μmoL/L vs 67.60±6.13 μmoL/L, t=2.253, P=0.027). After treatment, there was a slight increase in the level of TC in both the TAF group (5.60±0.89 mmol/L vs 5.18±0.85 mmol/L, t=2.076, P=0.041) and the combined group (5.45±0.80 mmol/L vs 5.02±0.83 mmol/L, t=2.269, P=0.026). There was no significant difference in the incidence rate of adverse reactions between the TAF group and the combined group (21.62% vs 18.92%, χ²=0.084, P=0.772). ConclusionFor ETV-treated CHB patients experiencing LLV, compared with sequential TAF therapy, the ETV+TAF combined therapy can effectively increase virologic response rate, alleviate liver fibrosis, and improve liver function, whereas sequential TAF therapy has less impact on renal function. Sequential or combined therapy with TAF may induce a slight increase in the level of TC, which should be taken seriously in clinical practice.
8.Effect and mechanism of transplantation of human umbilical cord mesenchymal stem cells with overexpression of the Numb gene in treatment of cholestatic liver fibrosis
Shihao ZHANG ; Changqing ZHAO ; Mingyan YANG ; Feifei XING ; Wei LIU ; Gaofeng CHEN ; Jiamei CHEN ; Ping LIU ; Yongping MU
Journal of Clinical Hepatology 2026;42(1):80-89
ObjectiveTo investigate the effect and mechanism of transplantation of human umbilical cord mesenchymal stem cell (hUC-MSC) with overexpression of the Numb gene in the treatment of cholestatic liver fibrosis (CLF). MethodsThe technique of lentiviral transfection was used to induce the overexpression of the Numb gene in hUC-MSC (hUC-MSCNumb-OE), and hUC-MSC transfected with empty vector (hUC-MSCOE-EV) was used as negative control. Bile duct ligation (BDL) was performed to establish a rat model of CLF, and then the rats were randomly divided into BDL group, hUC-MSC group, hUC-MSCOE-EV group, and hUC-MSCNumb-OE group, while a sham-operation group was also established. The rats in the intervention groups were given a single splenic injection of the corresponding cells after BDL, and samples were collected at the end of week 4. Related indicators were measured, including serum biochemistry, liver histopathology, the content of hydroxyproline (Hyp) in the liver, hepatic stellate cell activation, ductular reaction, liver regeneration, and the expression levels of key molecules in the Numb-p53 signaling axis. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the BDL group, the hUC-MSC group and the hUC-MSCOE-EV group had significant reductions in the levels of serum biochemical parameters (aspartate aminotransferase, gamma-glutamyl transpeptidase, total bile acid, total bilirubin, and direct bilirubin), liver fibrosis markers (the content of Hyp and the expression levels of alpha-smooth muscle actin, tumor necrosis factor-α, and transforming growth factor-beta 1), and ductular reaction markers (the expression levels of CK7 and CK19) (all P <0.05), and compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significantly greater improvements in the above indicators (all P <0.05). In addition, compared with the hUC-MSCOE-EV group, the hUC-MSCNumb-OE group had significant improvements in the expression levels of liver regeneration-related markers (albumin and hepatocyte nuclear factor 4α) and the molecules associated with the Numb-p53 signaling axis (Numb, pNumb, Mdm2, and p53) (all P <0.05). ConclusionOverexpression of the Numb gene can enhance the therapeutic effect of hUC-MSC on CLF, possibly by activating the Numb-PTBL-p53-HNF4α axis, promoting the hepatic differentiation of hUC-MSCs and subsequently enhancing liver regeneration.
9.Jianpi Qinghua Formula improves metabolic-associated fatty liver disease by modulating PGC1α/PPARα/CPT1A pathway.
Yan-Yan XIAO ; Xu HAN ; Qing-Guang CHEN ; Jun-Fei XU ; Chi CHEN ; Fan GONG ; Hao LU
China Journal of Chinese Materia Medica 2025;50(9):2505-2514
Based on the regulation of mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway, this study investigated the effect of Jianpi Qinghua Formula on the mitochondrial fatty acid β-oxidation pathway in the livers of mice with metabolic-associated fatty liver disease(MAFLD) induced by a high-fat diet. MAFLD mice were fed a high-fat diet to establish the model, and after successful modeling, the mice were divided into the model group, the Jianpi Qinghua Formula group, and the metformin group, with an additional control group. Each group was treated with the corresponding drug or an equivalent volume of saline via gavage. Body mass and food intake were measured regularly during the experiment. At the end of the experiment, blood lipid levels and liver function-related indices were measured, liver pathological changes were observed, and protein expression levels of PGC1α, PPARα, PPARγ, and CPT1A were detected by Western blot. The results showed that, with no difference in food intake, compared to the model group, the body mass of the Jianpi Qinghua Formula group and the metformin group was reduced, liver weight and liver index decreased, and levels of cholesterol, triglycerides, and low-density lipoprotein cholesterol(LDL-C) were lowered. Additionally, a decrease in alanine aminotransferase(ALT) and aspartate aminotransferase(AST) was observed. Hematoxylin and eosin(HE) staining revealed reduced pathological damage to hepatocytes, while oil red O staining showed improvement in fatty infiltration. The liver disease activity score decreased, and transmission electron microscopy revealed improvement in mitochondrial swelling and restoration of internal cristae. Western blot analysis indicated that Jianpi Qinghua Formula significantly increased the expression of PGC1α, PPARα, and CPT1A proteins in the liver and reduced the expression of PPARγ. These results suggest that the Jianpi Qinghua Formula improves mitochondrial function, promotes fatty acid oxidation, and alleviates the pathological changes of MAFLD. In conclusion, Jianpi Qinghua Formula can improve MAFLD by mediating mitochondrial fatty acid β-oxidation through the PGC1α/PPARα/CPT1A pathway.
Animals
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PPAR alpha/genetics*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Carnitine O-Palmitoyltransferase/genetics*
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Male
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Liver/metabolism*
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Fatty Liver/genetics*
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Humans
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Mice, Inbred C57BL
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Diet, High-Fat/adverse effects*
10.Tanreqing Capsules protect lung and gut of mice infected with influenza virus via "lung-gut axis".
Nai-Fan DUAN ; Yuan-Yuan YU ; Yu-Rong HE ; Feng CHEN ; Lin-Qiong ZHOU ; Ya-Lan LI ; Shi-Qi SUN ; Yan XUE ; Xing ZHANG ; Gui-Hua XU ; Yue-Juan ZHENG ; Wei ZHANG
China Journal of Chinese Materia Medica 2025;50(8):2270-2281
This study aims to explore the mechanism of lung and gut protection by Tanreqing Capsules on the mice infected with influenza virus based on "the lung-gut axis". A total of 110 C57BL/6J mice were randomized into control group, model group, oseltamivir group, and low-and high-dose Tanreqing Capsules groups. Ten mice in each group underwent body weight protection experiments, and the remaining 12 mice underwent experiments for mechanism exploration. Mice were infected with influenza virus A/Puerto Rico/08/1934(PR8) via nasal inhalation for the modeling. The lung tissue was collected on day 3 after gavage, and the lung tissue, colon tissue, and feces were collected on day 7 after gavage for subsequent testing. The results showed that Tanreqing Capsules alleviated the body weight reduction and increased the survival rate caused by PR8 infection. Compared with model group, Tanreqing Capsules can alleviate the lung injury by reducing the lung index, alleviating inflammation and edema in the lung tissue, down-regulating viral gene expression at the late stage of infection, reducing the percentage of neutrophils, and increasing the percentage of T cells. Tanreqing Capsules relieved the gut injury by restoring the colon length, increasing intestinal lumen mucin secretion, alleviating intestinal inflammation, and reducing goblet cell destruction. The gut microbiota analysis showed that Tanreqing Capsules increased species diversity compared with model group. At the phylum level, Tanreqing Capsules significantly increased the abundance of Firmicutes and Actinobacteria, while reducing the abundance of Bacteroidota and Proteobacteria to maintain gut microbiota balance. At the genus level, Tanreqing Capsules significantly increased the abundance of unclassified_f_Lachnospiraceae while reducing the abundance of Bacteroides, Eubacterium, and Phocaeicola to maintain gut microbiota balance. In conclusion, Tanreqing Capsules can alleviate mouse lung and gut injury caused by influenza virus infection and restore the balance of gut microbiota. Treating influenza from the lung and gut can provide new ideas for clinical practice.
Animals
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Drugs, Chinese Herbal/administration & dosage*
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Mice
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Lung/metabolism*
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Mice, Inbred C57BL
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Capsules
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Orthomyxoviridae Infections/virology*
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Gastrointestinal Microbiome/drug effects*
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Male
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Humans
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Female
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Influenza A virus/physiology*
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Influenza, Human/virology*


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