Vascular calcification(VC)is a major cause of cardiovascular disease morbidity and mortality in diabetic patients,and it is one of the core pathological features of diabetes-induced vascular damage and remodeling1.Although several mechanisms,such as oxidative stress and inflammation,have been proposed to play a role in the occurrence and development of VC,and treatment strategies targeting these underlying factors have been developed,the effectiveness of these therapies remains limited and faces many challenges.

Introduction:Atherosclerosis (AS) is driven by lipid accumulation, inflammation, and oxidative stress, leading to endothelial dysfunction and plaque formation. Emerging evidence indicates that iron overload and ferroptosis exacerbate these processes via enhanced lipid peroxidation and vascular injury. However, current Western medical strategies predominantly target lipid-lowering and inflammation, often overlooking iron dysregulation and ferroptotic pathways. Methods:We used ApoE-/- mice as an AS model and administered Tetramethylpyrazine (TMP), Paeoniflorin (PF), or their combination (TMP+PF). Serum lipids, oxidative stress biomarkers, iron metabolism indices, and ferroptosis-related markers were measured. Results:Both TMP and PF significantly reduced serum lipid levels and oxidative stress, normalized iron metabolism parameters, and suppressed ferroptosis-associated markers, indicating a protective effect against ferroptotic damage. Discussion:These findings suggest that TMP and PF mitigate AS by coordinately regulating oxidative stress, iron homeostasis, and ferroptosis. Their multi-targeted action may offer a complementary approach to conventional therapies, addressing the previously neglected mechanisms of iron-driven vascular pathology.

AIMS:Circular RNAs (circRNAs) play important roles in cancer. However, their roles in pancreatic ductal adenocarcinoma (PDAC) progression and therapeutic resistance are underexplored. Here, we investigated the roles and diagnostic potential of circGANAB in PDAC. METHODS:The level of circGANAB was examined in PDAC cell lines, tumor tissues and serum exosomes. A receiver operating characteristic curve was constructed to evaluate the diagnostic performance of circGANAB. The oncogenic roles of circGANAB in PDAC tumor growth, metastasis, and immunotherapy resistance were studied in mouse tumor models. CircRNA-pulldown, followed by RNA sequencing, was performed to identify circGANAB-interacting RNAs. RNA stability assay was performed to investigate the roles of circGANAB in regulating its interacting RNAs. RESULTS:CircGANAB was upregulated in PDAC cell lines, primary tumors and was further upregulated in metastatic tumors, with a positive link to the tumor size and poor prognosis. CircGANAB promoted PDAC cell growth, ferroptosis resistance, and metastasis. Furthermore, circGANAB limited anti-PD-L1 immunotherapy efficacy by inhibiting CD4+ and CD8+ T cell infiltration. Mechanistically, circGANAB directly interacted with tumor suppressive lncRNAs GAS5, lncLDAH3, and TMEM51-AS1 and mRNAs IL-13 and IL-17D, resulting in RNA degradation. Additionally, serum exosomal circGANAB significantly increased with good diagnostic performance as a non-invasive biomarker. Exosome-mediated intratumoral transfer of the oncogenic circGANAB promoted PDAC progression. CONCLUSIONS:The upregulated circGANAB holds promising potential as a novel diagnostic biomarker in PDAC. CircGANAB promotes PDAC tumor growth, metastasis, and immunotherapy resistance through degrading interacting RNAs. These results highlight the significance of circRNAs in the tumor microenvironment and the circRNA-RNA interaction gene regulatory mechanisms underlying oncogenesis and tumor progression.

Abstract Background Hyperuricemia (HUA), characterized by elevated serum uric acid (SUA) level, serves as a precursor of gout. Gout formula (GF), an empirical formula, has been prescribed in Chinese medicine practice for many years and observed to be effective in relieving HUA and gout. This study aimed to investigate GF as an innovative therapeutic agent for HUA and to elucidate its underlying molecular mechanisms using in vivo and in vitro models of HUA. Methods A HUA mouse model was established by orally administering potassium oxonate (PO) and injecting with hypoxanthine (HX) to mice. Behavioral tests and histopathological analysis were performed to measure the efficacy of GF. Biochemical indicators such as SUA, urine uric acid (UA), xanthine oxidase (XOD), blood urea nitrogen (BUN), and creatinine (Cre), inflammatory markers, signaling pathway markers, uric acid transporters (UAT), and renal injury were assessed using enzyme-linked immunosorbent assay (ELISA), Western blot analysis, immunofluorescence staining, and real-time PCR analyses as appropriate. HK-2 cells stimulated with monosodium urate (MSU) were used to confirm the action mechanisms of GF against HUA. Results GF treatment significantly reduced the pain sensitivity and improved the tensile performance of the PO + HX-treated mice in the hot plate test and grip strength test, respectively. GF treatment also significantly reduced the levels of UA, BUN, and Cre, and alleviated the kidney injury induced by PO + HX in mice. In addition, GF suppressed inflammatory response by attenuating the protein expressions of CCR2, CCR5, CXCL10, TNF-α, IL-4, IL-6, and IL-1β, but upregulating AMPK phosphorylation. It also modulated the UAT by increasing OAT1 and OAT3, while decreasing URAT1 and GLUT9 protein expression. Moreover, increasing GF concentrations led to a decreased intracellular UA level, but increased extracellular UA in the MSU-stimulated HK-2 cells, consisting with the findings in the in vivo study. Furthermore, GF also mitigated the inflammation-induced pyroptosis of HK-2 cells, and AICAR, an AMPK agonist, enhanced GF in suppressing the pyroptosis via inhibiting the activation of AMPK-TLR4-NLRP3 pathway. Conclusions GF significantly alleviated kidney injury and inflammatory response induced by HUA in mice, and the action involved inhibiting the activation of the XOD and pyroptosis, and modulating the expression of UAT through downregulating the TLR4-NF-κB p65-NLRP3 pathway. These findings amply indicate that GF is a promising therapeutic option for managing gout and kidney complications associated with HUA.

Ethnopharmacological Relevance:Chuanxiong (Ligusticum chuanxiong Hort.) and Chishao (Paeonia lactiflora Pall.) are widely used in Traditional Chinese Medicine (TCM) for their ability to promote blood circulation and resolve blood stasis, particularly in the treatment of cardiovascular diseases such as atherosclerosis (AS). Aim of The Study:This review systematically summarizes the potential mechanisms by which L. chuanxiong and P. lactiflora modulate iron metabolism, inhibit ferroptosis, and enhance blood flow, offering innovative strategies for the treatment of AS. Materials and Methods:A comprehensive literature search was performed using databases such as PubMed, Web of Science, and CNKI. We implemented a narrative review with explicit search strategies across regional databases that included specific keywords related to the pharmacological effects of Chuanxiong and Chishao, particularly their roles in iron metabolism and ferroptosis. Studies were selected based on predefined inclusion criteria, ensuring relevance and quality. The data were organized to summarize the mechanisms of action and therapeutic potential of these substances, while also incorporating insights from traditional medical texts, including classical TCM literature. Specific search strategy: SU=(("Atherosclerosis" [MeSH] OR "Atherosclerotic plaque" [Title/Abstract] OR "AS" [Title/Abstract] OR "Arteriosclerosis" [Title/Abstract]) AND ("Chuanxiong" [Title/Abstract] OR "Ligusticum chuanxiong" [MeSH]) AND ("Chishao" [Title/Abstract] OR "Paeonia lactiflora" [MeSH])) AND (("iron metabolism" [Title/Abstract] OR "ferroptosis" [MeSH] OR "lipid peroxidation" [Title/Abstract]) OR ("JAK-STAT pathway" OR "PI3K/AKT" OR "MAPK/NF-κB" OR "GPX4" [Title/Abstract]) AND ("randomized controlled trial" [Publication Type] OR "in vitro" [Title/Abstract] OR "in vivo" [Title/Abstract] OR "clinical study" [Title/Abstract])). Results:Ligusticum chuanxiong: and P. lactiflora modulate iron homeostasis by suppressing hepcidin and enhancing ferroportin, inhibit ferroptosis via GPX4 activation and System Xc- upregulation, and mitigate oxidative stress/inflammation through ROS scavenging and NF-κB suppression, collectively reducing atherosclerotic plaque instability. Conclusion:Chuanxiong and Chishao demonstrate significant potential as therapeutic agents for AS by targeting iron metabolism and ferroptosis. Their traditional use in TCM is supported by modern pharmacological evidence, highlighting their potential for integration into modern therapeutic frameworks.

Abstract Background The behavioral and psychological symptoms of dementia (BPSD) affect over 90% of dementia patients with no effective therapeutic interventions. The Modified Gan-Mai-Da-Zao Decoction (M-GMDZD) is an innovative formula derived from GMDZD, a classical herbal formula commonly prescribed by Chinese medicine (CM) practitioners for psychiatric conditions. Aim This study aimed to investigate the anti-BPSD effects such as sedative-hypnotic, anxiolytic, and antidepressant-like actions of M-GMDZD in animal models of BPSD. Methods M-GMDZD was subjected to the high-performance liquid chromatography (HPLC) for chemical characterization. To investigate the sedative-hypnotic effect of M-GMDZD, ICR mice were intragastrically administered with M-GMDZD for 14 days, followed by intraperitoneal pentobarbital injections. The pentobarbital-induced sleep test was performed to assess the sleep-improving properties of M-GMDZD in mice, while the monoamine neurotransmitter levels in the pentobarbital-treated mouse brains were measured by ELISA. To evaluate anxiolytic and anti-depressant-like effects of M-GMDZD, the bilateral common carotid arteries occlusion combined with chronic restraint stress (BCCAO/CRS) model in rats was established. After drug treatment for 21 days, rats were subjected to behavioral tests, including open field test (OFT), novel recognition test (NORT), sucrose preference test (SPT), forced swim test (FST), and social interaction test (SIT). The brain tissues from BCCAO/CRS rats were collected for biochemical analysis. Results M-GMDZD significantly prolonged the pentobarbital-induced sleep duration, increased the cerebral 5-hydroxytryptamine (5-HT) level and decreased the cerebral dopamine (DA) level in the pentobarbital-treated mice, showing promising sedative-hypnotic and sleep-improving effects. Moreover, M-GMDZD treatment markedly alleviated the anxiety-related behavioral impairments, ameliorated depression-like deficits, attenuated recognition memory impairments and improved social interaction in the BCCAO/CRS rats, as assessed by a battery of behavioral tests. The anxiolytic and antidepressant-like effects of M-GMDZD were partly attributed to the neurotrophin-3 (NT-3)-mediated neurotrophic mechanisms. We also found that M-GMDZD alleviated BPSD symptoms in BCCAO/CRS rats by restoring synaptic plasticity via the activation of TrkB/ERK/CREB pathway. Conclusions This study has demonstrated for the first time that M-GMDZD exhibits potent anti-BPSD properties, including sedative, anxiolytic, and antidepressant-like effects in preclinical models, highlighting its potential as a promising, multi-target therapeutic intervention for the BPSD management.

Oxyberberine (OBB) has good potential neuroprotective effects. However, the poor water solubility of OBB poses a challenge to its therapeutic effects. In this study, OBB-hydroxypropyl-β-cyclodextrin (OBB-β-CD) was prepared to increase the water solubility and improve bioavailability of OBB. The neuroprotective effects of OBB-β-CD against AD were investigated using 3×Tg transgenic AD mouse model. OBB-β-CD exhibited dual regulatory capabilities in improving both behavioral deficits and pathological features of AD. OBB-β-CD was more effective than OBB in modulating the amyloid precursor protein (APP) processing and inhibiting the hyperphosphorylation of Tau protein. OBB-β-CD was effective in reducing both the concentration of beta-amyloid 42 (Aβ42) and the deposition of Aβ plaques in 3×Tg mouse models. OBB-β-CD also suppressed neuroinflammation by promoting microglial polarization from an M1-like to an M2-like phenotype. Furthermore, OBB-β-CD restored the gut dysbiosis and inhibited the activation of the C-X-C motif chemokine receptor 3 (CXCR3) and the level of C-X-C motif chemokine ligand 10 (CXCL10) in the brain and colon tissues of 3×Tg mice. Simultaneously, the effect of OBB that suppressed microglial M1 and promoted M2 polarization to improve the neuronal micro-environment was verified in vitro using BV-2 cells. Importantly, OBB-β-CD showed similar anti-AD effects of knockdown of CXCR3 in 3×Tg mice, but no synergistic effects were observed in the shCXCR3 + OBB-β-CD group compared to the shCXCR3 group. Furthermore, the results of molecular docking and surface plasmon resonance (SPR) assay indicated that CXCR3 could bind with OBB. Additionally, the fecal microbiota transplantation (FMT) of fecal microbiota from the OBB-β-CD-treated 3×Tg mice (OBB-β-CD-FMT) significantly alleviated the cognitive deficits in the pseudo-germ-free 3×Tg mice via markedly suppressing the hyperphosphorylation of Tau protein, Aβ level and the activation of CXCR3 in the brain of 3×Tg mice. OBB-β-CD has good potential for further development into a therapeutic agent for AD treatment.

Objective To investigate the effects of a digital electric fire-needling acupuncture device (EFNA) in a mouse model of chronic eczema (CE) and aimed to elucidate its underlying antipruritic mechanisms. Methods Forty bagg albino (BALB)/c mice were randomly assigned to 4 groups: control, model, EFNA, and halometasone groups (n = 10). Except for the control group, CE was induced in all groups using 2,4-dinitrochlorobenzene. After model establishment, mice in the EFNA group received EFNA treatment at the lesional skin sites, whereas the halometasone group received a dose-tapering regimen of topical halometasone for two weeks. The eczema area severity index of the dorsal skin, and scratching frequency (bouts/10 min) were assessed after model induction and treatment. The splenic index was recorded post-intervention. Hematoxylin and eosin staining evaluated skin morphology, and Western blot analysis determined expression levels of CXC motif chemokine ligand 10 (CXCL10), CXC chemokine receptor type 3 (CXCR3), mas-related g-protein coupled receptor member A3 (MrgprA3), and transient receptor potential vanilloid 1 (TRPV1) in skin tissue. Results Both EFNA and halometasone markedly reduced eczema area severity index scores (both P < .001), significantly decreased scratching frequency (P = .010, P = .007), and reduced the spleen index (P = .029, P < .001). EFNA also alleviated edema and epidermal thickening in lesional skin, decreased local lymphocyte infiltration, and downregulated CXCL10, CXCR3, MrgprA3, and TRPV1 expression in skin tissues (all P < .001). Conclusion EFNA ameliorated 2,4-dinitrochlorobenzene-induced chronic eczematous lesions, with reductions in pruritus, inflammatory edema and cellular infiltration, alongside downregulation of CXCL10, CXCR3, MrgprA3, and TRPV1. These findings suggest that the antipruritic effect of EFNA may involve modulation of the non-histaminergic itch transmission pathway, providing new insights into the mechanism of fire-needling therapy for CE.

Allergic rhinitis (AR) is a common allergic condition characterized by frequent sneezing, nasal congestion, nasal itching and rhinorrhea. Chinese medicine formula Yu-Ping-Feng Powder with Variation (YPV) is an empirical formula modified from an ancient Chinese medicine formula named Yu-Ping-Feng Powder, which is widely used for the treatment of allergic diseases such as AR and asthma. To evaluate the efficacy and safety of YPV on AR patients with the lung and spleen Qi deficiency type using a randomized, double-blind, placebo-controlled clinical trial (RCT). Between April 2022 and June 2023, a total of 58 participants were recruited and randomly allocated to receive either YPV (n = 29) or placebo (n = 29) for 8 consecutive weeks. The changes of the Total Nasal Symptom Score (TNSS), and the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) or the Paediatric Allergic Disease Quality of Life Questionnaire (PADQLQ) scores at week 8 were used as the primary outcomes. The secondary outcomes included (1) the change of TNSS at weeks 4, 12 and 16; (2) the RQLQ or the PADQLQ scores at weeks 4, 12 and 16; (3) the change of frequency of AR episodes and their severity Visual Analog Scale (VAS) at weeks 4, 8, 12 and 16; (4) the changes of the gut microbiota composition in stool samples at week 8; and (5) adverse events related to the study treatment. YPV treatment could significantly improve the RQLQ score in AR patients at weeks 4, 8, 12, and 16 (p = 0.05, p = 0.04, p = 0.04 and p = 0.03, respectively), when compared with the placebo treatment. However, it did not improve the TNSS score at week 8 in AR patients when compared with the placebo group. In addition, YPV treatment could reduce the VAS score in AR patients at weeks 12 and 16 when compared with the placebo group, although the reductions were not statistically significant (p = 0.06 and p = 0.08, respectively). Importantly, no overt adverse effects were observed in both YPV and placebo groups. YPV was well-tolerated and could effectively ameliorate multiple symptoms of AR and improve the quality of life of AR patients after 8-week treatment. Trial registration ClinicalTrials.gov, NCT04976023. Registered 26 July 2021, https://clinicaltrials.gov/study/NCT04976023?cond=The

Alzheimer’s disease (AD) is the primary cause of dementia in the elderly. However, effective therapies that modify the disease process in AD remain elusive. Far-infrared radiation (FIR) is commonly utilized as a complementary treatment a range of disease, for example insomnia and rheumatoid arthritis. In this research, we explored how FIR light impacts the cognitive functions of TgCRND8 AD mice and elucidated its underlying molecular mechanism. The cognitive capabilities of TgCRND8 mice assessed by employing the Morris water maze. The concentrations of IL-1β, TNF-α, IL-4, Aβ40, and Aβ42 protein were assessed by enzyme-linked immunosorbent assay. Immunostaining was conducted to assess the Aβ deposits and microglial presence in the brains of TgCRND8 mice. Western blot was applied to detect the protein expressions of tau phosphorylation, amyloid-β (Aβ) production, Jak-2/Stat3, and Nrf-2/HO-1 pathways. The results indicated that FIR light notably ameliorated the cognitive impairments of the AD mice, reduced both Aβ deposition and tau protein hyperphosphorylation at sites of Thr205, Ser369, Ser404, and Thr181, suppressed the release of TNF-α and IL-1β, attenuated the ratios of p-Jak-2/Jak-2 and p-Stat3/Stat3, while increased the protein levels of IL-4, Nrf-2, and HO-1 in the brains of TgCRND8 mice. These findings amply demonstrated that FIR light ameliorated cognitive deficits of TgCRND8 mice via reducing both Aβ burden and tau protein hyperphosphorylation, suppressing the neuroinflammation, and restoring the levels of the oxidative-related proteins through modulating Jak-2/Stat3 and Nrf-2/HO-1 pathways. These experimental findings indicate that FIR light treatment is a promising treatment approach for AD.

Abstract Objective: Yokukansan (YKS) is a traditional formula for neurological conditions, effectively addressing anxiety and depression symptoms. This study aims to investigate the antidepressant effects of YKS on chronic unpredictable mild stress (CUMS)-induced depressive-like behavior in rats, focusing on the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3 beta (GSK3 β) pathway. Materials and Methods: Rats underwent the 6 weeks-CUMS model; YKS was administered at three doses in the last 2 weeks; Fluoxetine-positive control. Depressive behaviors are assessed using the open field test, forced swim test (FST), and sucrose preference test. Neurotrophic factors (brain-derived neurotrophic factor [BDNF] and nerve growth factor [NGF]), inflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-6 [IL-6], IL-1 β, and IL-10), neurotransmitters (5-hydroxytryptamine [5-HT], dopamine, and gamma-aminobutyric acid), and cortisol were measured. The PI3K/Akt/GSK3 β pathway was analyzed by Western blot and validated by a code for a compound that inhibits AKT (MK-2206). Neuronal integrity in the hippocampus and astrocyte/microglial activation were examined with Nissl staining and immunohistochemistry. Results: Results are expressed as means ± standard error of the mean one-way analysis of variance was used, with P < 0.05 considered significant. YKS improved depressive-behavior in CUMS rats by increasing sucrose preference ( P < 0.01) and reduced FST immobility ( P < 0.01). YKS restored BDNF and NGF levels ( P < 0.05), reduced TNF-α ( P < 0.01), IL-6, and IL-1β ( P < 0.05), raised 5-HT ( P < 0.05), dopamine ( P < 0.0001), decreased cortisol ( P < 0.001), and improved astrocyte/microglial activation. YKS-activated PI3K/Akt/GSK3 β signaling increased p-Akt and p-GSK3 β ( P < 0.05); effects were blocked by MK-2206 ( P < 0.01). Conclusions: YKS shows antidepressant potential by boosting BDNF and NGF, reducing pro-inflammatory cytokines, and protecting neurons via the PI3K/Akt/GSK3 β pathway. It restores neurotransmitters, lowers cortisol, and alleviates stress, supporting YKS as a therapy for depression.

Amyloid-beta (Aβ) aggregation, phosphorylated tau accumulation and neuroinflammation are considered as three hallmarks of Alzheimer’s disease (AD). Rhynchophylline (RN), the major alkaloid of a Chinese medicinal plant Uncaria rhynchophylla, has been shown to possess potent anti-AD effects. This study explored the effects of RN on Aβ pathology, tauopathy, and neuroinflammation using three AD mouse models, including TgCRND8, 3×Tg-AD, and 5×FAD, with RN treatment lasting for 4, 6, and 6 months, respectively, followed by behavioral tests and biological assays. In addition, BV2 cells were employed to further evaluate the biological effects of RN. RN treatment improved cognitive functions by reducing anxiety-like behaviors, enhancing recognition ability, and ameliorating learning impairments. It modulated Aβ processing through reducing the Aβ-producing enzyme activities and enhancing degradation enzyme activities, thereby diminishing Aβ accumulation. RN also decreased hyperphosphorylated tau proteins at Thr181, Thr205, Ser396, and Ser404 sites. Moreover, RN diminished neuroinflammation by reducing microglia and astrocyte activation and lowering the release of inflammatory cytokines. Furthermore, RN treatment could restore gut microbiota dysbiosis in 5×FAD mice. In BV2 cells, knockdown of p53, HDAC2, and Galectin-3 markedly enhanced the anti-inflammatory effects of RN. Overall, the anti-AD properties of RN were attributed to its regulation of multiple biological pathways, including regulation of the p53/PINK1 signaling pathway, inhibition of the HDAC2/AMPK signaling pathway, suppression of the Galectin-3/C/EBPβ/AEP signaling pathway, and modulation of gut microflora dysbiosis. This pioneering study unambiguously revealed the effects of RN on cognitive impairments, APP processing, tauopathy, and neuroinflammation in different transgenic mouse models with differing AD burdens, highlighting its potential as an anti-AD therapeutic agent and enhancing the scientific basis for its clinical use in treating AD.

OBJECTIVE:Enhancing innate immunity through interferons (IFNs) and IFN-stimulated genes (ISGs) offers a promising strategy for preventing herpes simplex virus type 1 (HSV-1) infection. Prunella vulgaris L., a medicinal herb, has demonstrated significant anti-HSV activity; in particular, its derived polysaccharide complex (PVE30) effectively inhibits viral replication. In this study, we investigate whether PVE30 exerts an anti-HSV-1 activity through activation of the innate immune response. METHODS:To determine the primary stage at which PVE30 exerts its effects during the HSV-1 life cycle, plaque reduction assays were conducted. Viral infection was further assessed by investigating the DNA copies, mRNA levels and protein expression of HSV-1 in infected cells using real-time polymerase chain reaction (RT-PCR) and Western blotting. The activation of the innate immune response was evaluated by detecting mRNA levels of ISGs, including MX dynamin-like GTPase 1 (Mx1), Mx2, 2'-5'-oligoadenylate synthetase 1 (OAS1), ISG15 and IFN regulatory factor 7 (IRF7) using RT-PCR, and levels of TANK-binding kinase 1 (TBK1) and IRF3 proteins using Western blotting. The translocation of phosphorylated IRF3 and stimulator of IFN genes (STING) was observed through fluorescence microscopy. RESULTS:PVE30 pre-treatment exerted protective effects against HSV-1 infection in human immortalized keratinocytes by enhancing the innate immune response. This was shown by increased transcriptional levels of IFN-β and antiviral ISGs, along with a significant reduction in HSV-1 DNA copies, mRNA expression and protein levels. Mechanistically, PVE30 promoted TBK1 phosphorylation, leading to nuclear translocation of IRF3 and subsequent IFN-β transcription; these effects were diminished by TBK1 inhibitor GSK8612. Additionally, STING was identified as a key mediator in PVE30-activated TBK1 signaling, as its inhibition induced by C-176 reduced PVE30's efficacy. CONCLUSION:This study elucidated the molecular mechanisms underlying the protective effects of PVE30 against HSV-1 infection. PVE30 exerted its protective role by enhancing STING-TBK1-IRF3 pathway-mediated innate immune response. Please cite this article as: Zhang YB, Xu L, Yuan M, Liu MF, Li Y, Zhong XL, Lin ZX, Xian YF, Lu P, Xi ZC, Xu HX. Protective effects of Prunella vulgaris polysaccharides against herpes simplex virus type 1 infection through the STING-TBK1-IRF3 pathway. J Integr Med. 2026; 24(3):454-465.

OBJECTIVE:To evaluate the clinical efficacy and safety of electroacupuncture (EA) and electroacupuncture combined with warm needling (EAWN) on reducing tinnitus loudness and tinnitus-related distress among older adults. METHODS:This multicenter, assessor-blinded, parallel-group, randomized clinical trial was conducted from December 2022 to April 2024 at three out-patient clinics in Hong Kong. Ninety eligible participants aged 50-70 years with subjective tinnitus for 0.5-24 months were equally randomized to EA, EAWN, or waitlist groups. Both treatment groups received two standardized treatment sessions per week for 5 weeks. The waitlist group received no treatment during the study period. The outcome measures were numeric rating scale (NRS) scores for tinnitus loudness, Tinnitus Handicap Inventory (THI) scores, and safety outcomes. Assessments were conducted at baseline, weeks 5 and 10. RESULTS:Both EA and EAWN groups showed significantly greater reductions in NRS scores for tinnitus loudness than did the waitlist group at weeks 5 (mean difference [95 % confidence interval]; EA: -1.91 [-2.79 to -1.03]; P < 0.001; EAWN: -1.81 [-2.68 to -0.94]; P < 0.001) and 10 (EA: -2.03 [-2.95 to -1.11]; P < 0.001; EAWN: -1.98 [-2.92 to -1.04]; P < 0.001). Improvements in total THI scores were also greater in the intervention groups at weeks 5 (P < 0.01) and 10 (P < 0.001). The two intervention groups showed no significant differences. No serious adverse events were reported. CONCLUSION:Both EA and EAWN therapies could be effective and safe treatments for subjective tinnitus in older adults.

BACKGROUND:Irritable bowel syndrome with diarrhea (IBS-D) presents significant treatment challenges due to limited therapeutic options that effectively target the underlying pathophysiological mechanisms. In this study, we performed a multi-center, double-blind randomized placebo-controlled trial to investigate the efficacy and safety of herbal medicine JCM-16021 on IBS-D with a focus on its effects on gut microbiota. RESULTS:Our study assessed the clinical efficacy and safety of JCM-16021 in alleviating abdominal pain in IBS-D patients. The results suggested that JCM-16021 is both effective and safe, with its therapeutic effects closely linked to the modulation of short-chain fatty acid (SCFA) producers. Through fecal microbiota transplantation (FMT) experiments in mice, we showed that SCFA producers mediate the alleviation of abdominal pain symptoms by the JCM-16021 treatment. In a TNBS-induced mouse model of IBS, we showed that butyrate producers enriched by JCM-16021 significantly ameliorate abdominal pain. Importantly, baseline gut microbial profiles, such as the presence of Eubacterium rectale in IBS-D patients are predictive of their responses to JCM-16021 treatment. CONCLUSIONS:Our findings not only affirm the efficacy of JCM-16021 in mitigating abdominal pain in IBS-D patients but also highlight a microbiota-dependent mechanism, underscoring the therapeutic potential of gut microbiota modulation in treating gastrointestinal disorders. By combining clinical trials in humans with biological experiments in mice, this study establishes a translational approach to investigate the role of gut microbiota in the treatment of herbal medicine. CLINICALTRIALS:gov no: NCT03457324.

Fructose is a nutrient used widely and indiscriminately as a sweetener in various types of foods and beverages. Accumulating evidence suggests that dietary fructose has a close relationship with metabolic diseases like hyperuricemia (HUA). However, the role and metabolic fate of fructose intake remain elusively obscure. The present work made a pioneering endeavor to unravel the potential mechanistic link between prolonged fructose overconsumption and the incidence of HUA. High-fructose (30%) free drinking was provided to rats for 17 weeks. Results indicated that long-term high-fructose intake remarkably increased the levels of uric acid, creatinine, and urea. Besides, mild renal alteration induced by high fructose was observed in the hyperuricemic rats. Instead of activating ketohexokinase, high-fructose intake activated the pentose phosphate pathway (PPP) to produce abundant ribose 5-phosphate and phosphoribosyl pyrophosphate. The de novo purine biosynthesis (DNPB) was activated to produce purines and accelerate the purine cycle. High-fructose intake significantly enhanced the expression of core enzymes of DNPB and changed the purinosome formation and forming areas. Furthermore, up-regulation of xanthine oxidase (XOD) promoted the purine metabolism, resulting in increased levels of inosine monophosphate, inosine, hypoxanthine, and xanthine. Besides, the targeted metabolome analysis also showed that fructose metabolism triggered bioenergetic alteration with the consumption of ATP and a surge in NAD+ and NADH. Hence, chronic ingestion of high-fructose contributed to HUA, which was intimately associated with activation of original biosynthetic and metabolic pathways of endogenous purine simultaneously mediated by PPP, DNPB, and XOD and accompanied by bioenergetic alteration.

[This corrects the article DOI: 10.1016/j.toxrep.2024.101682.].

INTRODUCTION:The combined effect of some modifiable lifestyle factors on incident functional constipation (FC) is uncertain. This study aimed to evaluate the combined association between healthy lifestyle behaviors and FC incidence. METHODS:This population-based prospective cohort study involved 107,457 adults aged 40-70 years who had no FC diagnosis at baseline from the UK Biobank study. The exposure was a sum of 5 healthy lifestyle behaviors: never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake. The outcome was the incidence of FC. The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for their associations. RESULTS:During a median follow-up of 11.7 years, 3,591 (3.3%) incident FC cases were recorded. Compared with not exhibiting any of the 5 healthy lifestyle behaviors, the multivariable adjusted HRs (95% CI) associated with having 1, 2, and 3-5 behaviors for FC incidence were 0.81 (0.74-0.90), 0.72 (0.65-0.80), and 0.60 (0.54-0.67), respectively ( P for trend <0.001). Never smoking (HR 0.83, 95% CI 0.77-0.88, P < 0.001), high level of vigorous physical activity (HR 0.79, 95% CI 0.74-0.85, P < 0.001), and optimal sleep (HR 0.79, 95% CI 0.71-0.87, P < 0.001) demonstrated significant independent inverse associations with FC incidence. DISCUSSION:Adopting a higher number of healthy lifestyle behaviors is significantly associated with a reduced incidence of FC in the middle-aged and elderly population, indicating their potential to be a primary prevention strategy. Future research should explore underlying mechanisms and replicate our investigation across diverse populations.

OBJECTIVE:This study aimed to evaluate the satisfaction of patients with and without COVID-19 when using traditional Chinese medicine (TCM) telemedicine during the pandemic in Hong Kong. METHODS:This was a cross-sectional study of 122 COVID-19 patients and 90 non-COVID-19 patients who utilized a TCM telemedicine service provided by The Chinese University of Hong Kong Chinese Medicine Specialty Clinic cum Clinical Teaching and Research Centre during March to April 2022. A Telemedicine Satisfaction Questionnaire, consisting of factors of Information Exchange and Patient Comfort, was administered via an online survey after video consultations. Patients' satisfaction on these aspects of satisfaction was assessed. Subgroup and linear regression analyses were conducted to explore patient characteristics associated with satisfaction with telemedicine. RESULTS:Overall patient satisfaction with Information Exchange was good (28.00 [4.00] out of 35), but rating on Patient Comfort was mediocre (21.00 [5.00] out of 35), with a clear preference for face-to-face consultation. Compared to non-COVID-19 patients, the total score for Information Exchange was slightly lower amongst those consulted for COVID-19, as a majority of them are new patients without a per-existing relationship with the clinician. Satisfaction tended to be higher among patients who were younger, female, better-educated, employed, and had complete COVID-19 vaccinations. CONCLUSIONS:Despite being fairly satisfied with the TCM telemedicine service, both COVID-19 and non-COVID-19 patients expressed a preference for face-to-face consultation. While improving clinician-patient interaction during video consultation is expected to improve communication quality, it is expected that demand for face-to-face TCM services will rebound in the post-COVID era.