BACKGROUND: Electroacupuncture (EA) treatment is efficacious in patients with respiratory disorders, although the mechanisms of its action in lung-function protection are poorly understood. This study aimed to explore the neuroanatomical mechanisms of EA stimulation at the BL13 acupoint (Feishu, EA-BL13) improvement in asthma. METHODS: Allergic asthma was induced by intranasal 2.0% ovalbumin (OVA) instillation combined with intraperitoneal injection of the 10.0% OVA. The levels of interleukin (IL)-4 and IL-5 were detected by enzyme-linked immunosorbent assay. Hematoxylin and eosin and periodic acid-schiff stain were used to evaluate inflammatory cell infiltration and mucus secretion. Cellular oncogene fos induction in neurons after EA stimulation was detected by immunofluorescent staining. The messenger RNA expression levels of adrenergic receptors were quantified with real-time polymerase chain reaction. RESULTS: EA improved airway inflammation and mucus secretion mainly by activating somatosensory-sympathetic pathways ( P <0.001). Briefly, the intermediolateral (IML) nuclei of the spinal cord received signals from somatic EA stimulation and then delivered the information via the sympathetic trunk to the lung. Excited sympathetic nerve endings in lung tissue released large amounts of catecholamines that specifically activated the β2 adrenergic receptor (β2AR) on T cells ( P <0.01) and further decreased the levels of IL-4 and IL-5 ( P <0.001) through the cyclic adenosine monophosphate/protein kinase A signaling pathway. CONCLUSION This study provided a new explanation and clinical basis for the use of EA-BL13 as a treatment for allergic asthma in both the attack and remission stages and other respiratory disorders related to airway inflammation.
Electroacupuncture/methods* ; Animals ; Asthma/immunology* ; Rats ; Rats, Sprague-Dawley ; Male ; Inflammation/therapy* ; Interleukin-4/metabolism* ; Interleukin-5/metabolism*

Type 2 diabetes mellitus(T2DM) is a prevalent metabolic and endocrine disorder. Long-term hyperglycemia can lead to severe chronic complications, imposing substantial economic burdens on both society and patients. Despite the availability of various hypoglycemic agents for clinical use, these agents often fail to meet the therapeutic needs of T2DM and its complications. Consequently, there is an urgent need for novel therapeutic strategies and drugs. Lithocarpus litseifolius(L. litseifolius), commonly referred to as "cordyceps on trees", has a long history of use in traditional medicine and can be applied in tea, sugar, and medicine. Research indicates that L. litseifolius extracts are rich in dihydrochalcones, including trilobatin, phloridzin, and phloretin, which exhibit a range of pharmacological activities, such as anti-inflammatory, antioxidant, hypoglycemic, hypolipidemic, hepatoprotective, and cardioprotective effects. These properties suggest potential applications in the treatment of T2DM and its complications. This review systematically compiled and organized the relevant literature from the past decade on dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts. It highlighted recent research progress regarding their role in treating T2DM and its complications through mechanisms such as reducing insulin resistance, regulating glucose transport, improving glucose and lipid metabolism, modulating enzyme activity, regulating gut microbiota, and alleviating inflammation and oxidative damage. The purpose of this review is to provide a reference and basis for future research on the prevention and treatment of T2DM and its complications using dihydrochalcones(trilobatin, phloridzin, and phloretin) from L. litseifolius extracts.
Chalcones/chemistry* ; Diabetes Mellitus, Type 2/metabolism* ; Humans ; Animals ; Elaeocarpaceae/chemistry* ; Drugs, Chinese Herbal/therapeutic use* ; Hypoglycemic Agents/chemistry* ; Plant Extracts/chemistry*

This study aimed to explore the therapeutic mechanisms of Colquhounia Root Tablets(CRT) in treating diabetic kidney disease(DKD) by integrating biomolecular network mining with animal model verification. By analyzing clinical transcriptomics data, an interaction network was constructed between candidate targets of CRT and DKD-related genes. Based on the topological eigenvalues of network nodes, 101 core network targets of CRT against DKD were identified. These targets were found to be closely related to multiple pathways associated with type 2 diabetes, immune response, and metabolic reprogramming. Given that immune-inflammatory imbalance driven by metabolic reprogramming is one of the key pathogenic mechanisms of DKD, and that many core network targets of CRT are involved in this pathological process, receptor for advanced glycation end products(RAGE)-reactive oxygen species(ROS)-phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT)-nuclear factor-κB(NF-κB)-NOD-like receptor family pyrin domain containing 3(NLRP3) signaling axis was selected as a candidate target for in-depth research. Further, a rat model of DKD induced by a high-sugar, high-fat diet and streptozotocin was established to evaluate the pharmacological effects of CRT and verify the expression of related targets. The experimental results showed that CRT could effectively correct metabolic disturbances in DKD, restore immune-inflammatory balance, and improve renal function and its pathological changes by inhibiting the activation of the RAGE-ROS-PI3K-AKT-NF-κB-NLRP3 signaling axis. In conclusion, this study reveals that CRT alleviates the progression of DKD through dual regulation of metabolic reprogramming and immune-inflammatory responses, providing strong experimental evidence for its clinical application in DKD.
Animals ; Diabetic Nephropathies/metabolism* ; Receptor for Advanced Glycation End Products/genetics* ; NF-kappa B/genetics* ; Signal Transduction/drug effects* ; Rats ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Phosphatidylinositol 3-Kinases/genetics* ; Reactive Oxygen Species/metabolism* ; Humans ; Plant Roots/chemistry* ; Rats, Sprague-Dawley ; Tablets/administration & dosage*

The study investigated the specific mechanism by which oxocrebanine, the anti-hepatic cancer active ingredient in Stephania hainanensis, inhibits the proliferation of hepatic cancer cells. Firstly, methyl thiazolyl tetrazolium(MTT) assay, 5-bromodeoxyuridine(BrdU) labeling, and colony formation assay were employed to investigate whether oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells. Propidium iodide(PI) staining was used to observe the oxocrebanine-induced apoptosis of HepG2 and Hep3B2.1-7 cells. Western blot was employed to verify whether apoptotic effector proteins, such as cleaved cysteinyl aspartate-specific protease 3(c-caspase-3), poly(ADP-ribose) polymerase 1(PARP1), B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), Bcl-2 homologous killer(Bak), and myeloid cell leukemia-1(Mcl-1) were involved in apoptosis. Secondly, HepG2 cells were simultaneously treated with oxocrebanine and the autophagy inhibitor 3-methyladenine(3-MA), and the changes in the autophagy marker LC3 and autophagy-related proteins [eukaryotic translation initiation factor 4E-binding protein 1(4EBP1), phosphorylated 4EBP1(p-4EBP1), 70-kDa ribosomal protein S6 kinase(P70S6K), and phosphorylated P70S6K(p-P70S6K)] were determined. The results of MTT assay, BrdU labeling, and colony formation assay showed that oxocrebanine inhibited the proliferation of HepG2 and Hep3B2.1-7 cells in a dose-dependent manner. The results of flow cytometry suggested that the apoptosis rate of HepG2 and Hep3B2.1-7 cells increased after treatment with oxocrebanine. Western blot results showed that the protein levels of c-caspase-3, Bax, and Bak were up-regulated and those of PARP1, Bcl-2, and Mcl-1 were down-regulated in the HepG2 cells treated with oxocrebanine. The results indicated that oxocrebanine induced apoptosis, thereby inhibiting the proliferation of hepatic cancer cells. The inhibition of HepG2 cell proliferation by oxocrebanine may be related to the induction of protective autophagy in hepatocellular carcinoma cells. Oxocrebanine still promoted the conversion of LC3-Ⅰ to LC3-Ⅱ, reduced the phosphorylation levels of 4EBP1 and P70S6K, which can be reversed by the autophagy inhibitor 3-MA. It is prompted that oxocrebanine can inhibit the proliferation of hepatic cancer cells by inducing autophagy. In conclusion, oxocrebanine inhibits the proliferation of hepatic cancer cells by inducing apoptosis and autophagy.
Humans ; Apoptosis/drug effects* ; Autophagy/drug effects* ; Cell Proliferation/drug effects* ; Hep G2 Cells ; Liver Neoplasms/genetics* ; Carcinoma, Hepatocellular/genetics* ; Caspase 3/genetics*

Wumei Pills, a classic traditional Chinese medicine(TCM) formula, are widely used in the treatment of biliary ascariasis and diarrhea. In recent years, studies have shown that Wumei Pills have advantages in the treatment of type 2 diabetes mellitus(T2DM), while there are no relevant reports that systematically evaluate the efficacy of Wumei Pills in the treatment of T2DM. This study addresses this issue by systematically evaluating the efficacy and safety of Wumei Pills, aiming to provide an evidence-based basis for clinical practice. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, Wanfang, and VIP were researched for the randomized controlled trial(RCT) involving Wumei Pills for the treatment of T2DM that were published from inception to September 2024. RevMan 5.3 was used for the Meta-analysis of the data. A total of 18 RCTs were included, with a total of 1 437 patients. Meta-analysis produced the following results.(1)Treatment group outperformed control group in terms of overall response rate(RR=1.28, 95%CI[1.14, 1.43], P<0.000 1), fasting blood glucose(FPG)(WMD=-0.69, 95%CI[-0.93,-0.46], P<0.000 01), two-hour postprandial plasma glucose(2hPG)(WMD=-0.74, 95%CI[-1.17,-0.31], P<0.000 7), glycated hemoglobin(HbA1c)(WMD=-0.39, 95%CI[-0.60,-0.18], P=0.000 3), high-density lipoprotein(HDL)(WMD=0.38, 95%CI[0.28, 0.48], P<0.000 01), and body mass index(BMI)(WMD=-1.41, 95%CI[-2.40,-0.42], P=0.005).(2)The two groups had comparable effects regarding total cholesterol(TC)(WMD=-0.53, 95%CI[-1.13, 0.08], P=0.09) and low-density lipoprotein(LDL)(WMD=-0.25, 95%CI[-0.56, 0.06], P=0.12).(3)Triglycerides(TG)(WMD=-0.28,95%CI [-0.59,0.03],P=0.08), sensitivity analysis showed potential reduction effect(WMD=-0.20,95%CI[-0.36,-0.04],P=0.01). Occurrence of adverse drug reaction(RR=0.43,95%CI [0.23,0.80],P=0.007), sensitivity analysis showed significant disappearance(RR=0.56,95%CI[0.26,1.22],P=0.14), suggesting that the efficacy of treatment group was not better than that of control group. The results indicate that the treatment of T2DM with Wumei Pills is greatly related to the improvement of glucose metabolism, lipid metabolism, and clinical efficacy. The findings provide a basis for clinical application of Wumei Pills in treating T2DM, while the conclusion remains to be verified by clinical studies with higher quality.
Humans ; Diabetes Mellitus, Type 2/blood* ; Drugs, Chinese Herbal/administration & dosage* ; Randomized Controlled Trials as Topic ; Blood Glucose/metabolism* ; Hypoglycemic Agents/therapeutic use* ; Treatment Outcome ; Glycated Hemoglobin/metabolism* ; Female

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals

Metachromatic leukodystrophy (MLD) is an inherited disease caused by a deficiency of the enzyme arylsulfatase A (ARSA). Lentivirus-modified autologous hematopoietic stem cell gene therapy (HSCGT) has recently been approved for clinical use in pre and early symptomatic children with MLD to increase ARSA activity. Unfortunately, this advanced therapy is not available for most patients with MLD who have progressed to more advanced symptomatic stages at diagnosis. Patients with late-onset juvenile MLD typically present with a slower neurological progression of symptoms and represent a significant burden to the economy and healthcare system, whereas those with early onset infantile MLD die within a few years of symptom onset. We conducted a pilot study to determine the safety and benefit of HSCGT in patients with postsymptomatic juvenile MLD and report preliminary results. The safety profile of HSCGT was favorable in this long-term follow-up over 9 years. The most common adverse events (AEs) within 2 months of HSCGT were related to busulfan conditioning, and all AEs resolved. No HSCGT-related AEs and no evidence of distorted hematopoietic differentiation during long-term follow-up for up to 9.6 years. Importantly, to date, patients have maintained remarkably improved ARSA activity with a stable disease state, including increased Functional Independence Measure (FIM) score and decreased magnetic resonance imaging (MRI) lesion score. This long-term follow-up pilot study suggests that HSCGT is safe and provides clinical benefit to patients with postsymptomatic juvenile MLD.
Humans ; Leukodystrophy, Metachromatic/genetics* ; Pilot Projects ; Genetic Therapy/methods* ; Hematopoietic Stem Cell Transplantation ; Male ; Follow-Up Studies ; Female ; Lentivirus/genetics* ; Child ; Child, Preschool ; Hematopoietic Stem Cells/metabolism* ; Cerebroside-Sulfatase/metabolism* ; Adolescent

OBJECTIVE: Resveratrol (Res) is a promising anticancer drug against hepatocellular carcinoma (HCC), but whether its anti-HCC effects implicate mitophagy remains unclear. Therefore, we aimed to explore the specific role of Res in mitophagy and the related mechanisms during the treatment of HCC. METHODS: HepG2 cells and tumor-grafted nude mice were used to investigate the effects of low-, middle- and high-dose of Res on HCC progression and mitophagy in vitro and in vivo, respectively. A series of approaches including cell counting kit-8, flow cytometry, wound healing and transwell assays were used to evaluate tumor cell functions. Transmission electron microscopy, immunofluorescence and Western blotting were used to assess mitophagy. Mitochondrial oxygen consumption rate, reactive oxygen species and membrane potential were used to reflect mitochondrial function. After disrupting the expression of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), miR-143-3p, and ribonucleoside reductase M2 (RRM2), the effects of the MALAT1/miR-143-3p/RRM2 axis on cell function and mitophagy under Res treatment were explored in vitro. Additionally, dual-luciferase reporter and chromatin immunoprecipitation were used to confirm interactions between target genes. RESULTS: Res significantly inhibited the proliferation and promoted apoptosis of HCC cells in vitro, while significantly suppressing tumor growth in a dose-dependent manner and inducing mitophagy and mitochondrial dysfunction in vivo. Interestingly, MALAT1 was highly expressed in HCC cells and its knockdown upregulated miR-143-3p expression in HCC cells, which subsequently inhibited RRM2 expression. Furthermore, in nude mice grafted with HCC tumors and treated with Res, the expression of MALAT1, miR-143-3p and RRM2 were altered significantly. In vitro data further supported the targeted binding relationships between MALAT1 and miR-143-3p and between miR-143-3p and RRM2. Therefore, a series of cell-based experiments were carried out to study the mechanism of the MALAT1/miR-143-3p/RRM2 axis involved in mitophagy and HCC; these experiments revealed that MALAT1 knockdown, miR-143-3p mimic and RRM silencing potentiated the antitumor effects of Res and its activation of mitophagy. CONCLUSION Res facilitated mitophagy in HCC and exerted anti-cancer effects by targeting the MALAT1/miR-143-3p/RRM2 axis. Please cite this article as: Feng CY, Cai CS, Shi XQ, Zhang ZJ, Su D, Qiu YQ. Resveratrol promotes mitophagy via the MALAT1/miR-143-3p/RRM2 axis and suppresses cancer progression in hepatocellular carcinoma. J Integr Med. 2025; 23(1): 79-91.
Humans ; MicroRNAs/genetics* ; Liver Neoplasms/metabolism* ; Carcinoma, Hepatocellular/metabolism* ; Mitophagy/drug effects* ; Resveratrol/pharmacology* ; Animals ; Mice, Nude ; RNA, Long Noncoding/genetics* ; Hep G2 Cells ; Mice ; Disease Progression ; Mice, Inbred BALB C

The pathogenesis of depression is complex, and some existing monoamine antidepressants have problems such as drug resistance or off-target failure. Traditional Chinese medicine has the characteristics of "multi-component and multi-target", and has been used in the treatment of depression in clinical practice. Yueju pill is effective in the treatment of depression. Geniposide and ligustrazine, the active ingredients of Gardeniae fructus and Ligusticum sinense 'Chuanxiong', play a key role in the treatment of depression. In this study, based on the neuroprotective activity of genipin and the rapid antidepressant activity of tetramethylpyrazine, a series of novel genipin derivatives were designed and synthesized through pharmacophore assembly principle, and their neuroprotective activity and antidepressant effect were investigated. The results showed that the novel genipin derivatives had well neuroprotective activity on the glutamate-induced HT-22 cell model, with compounds W-1 and W-3 showing better protective activity. In behavioral despair depression (BDD) model mice, compound W-3 was found to have better antidepressant activity than W-1 in tail suspension test and forced swimming test. Further study on the behavior of chronic unpredictable mild stress (CUMS) model mice showed that W-3 could significantly improve the depression-like behavior of model mice. All animal experiments were approved by the Experimental Animal Ethics Committee of Anhui University of Chinese Medicine (approval number: AHUCM-mouse-2022027). The effects of the preferred compound W-3 on protein kinase A (PKA), cAMP response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), 5-hydroxytryptamine 1A (5-HT_1A) receptor, N-methyl-D-aspartate ionic glutamate receptor 2A (GluN2A) and N-methyl-D-aspartate ionic glutamate receptor 2B (GluN2B) were analyzed by Western blot. W-3 treatment significantly up-regulated the protein expression of PKA, CREB, BDNF and 5-HT_1A, and down-regulated the protein expression of GluN2A and GluN2B. The results of qRT-PCR were consistent with those of Western blot. According to the above results, compound W-3 has a potential antidepressant effect, and its mechanism may be related to the activation of PKA-CREB-BDNF signaling pathway by regulating the expression of GluN2A, GluN2B and 5-HT_1A receptor proteins.

Objective To observe the effect of multi-modal hand hygiene(HH)intervention on HH compliance,as well as the relationship between HH compliance and the healthcare-associated(HA)case infection incidence.Methods From 2014 to 2022,the infection control team in a tertiary first-class hospital implemented multi-modal HH intervention for health care workers(HCWs).The changing trend of HH monitoring data,the correlation be-tween HH compliance rate and HA case infection incidence were analyzed retrospectively.Results The consump-tion of HH products in the wards showed a stable upward trend;HH compliance rate increased from 64.98％in 2014 to 85.01％in 2022(P＜0.001),and HA case infection incidence decreased from 1.21％to 0.83％(P＜0.05).HH compliance rate was negatively correlated with HA case infection incidence(r=-0.369,P=0.027).HH compliance rates in different regions and job posts in each quarter were increased(P＜0.001).For 5 different HH moments in each quarter,HH compliance rate fluctuated slightly before sterile manipulation and after touching patient;presented rising trend after touching surroundings around patient,and decreased before touching patient and after touching patient's body fluid since 2020(P＜0.001).Conclusion Multi-modal HH intervention can im-prove the HH compliance of HCWs,improving their HH awareness is conducive to reducing HA case infection incidence.