BACKGROUND:Major depressive disorder (MDD) is characterized by interacting neuro-immune, metabolic, and oxidative stress pathways. Here, we examine the interactions between the acute phase (AP) response and serum lipids in Chinese MDD patients. METHODS:This case-control study assessed serum lipids and the AP response in 125 MDD patients and 40 healthy controls (HC), while controlling for metabolic confounders, including metabolic syndrome. RESULTS:We found an impaired lipid profile in MDD, characterized by reduced levels of high-density lipoprotein cholesterol (HDL), apolipoprotein (Apo) A1, chloromethyl phenylacetate (CMPA)ase activity, a reverse cholesterol transport (RCT) index, and increased ApoB/ApoA1 index. MDD was characterized by an AP response as conceptualized by lower serum albumin and transferrin and increased monomeric C-reactive protein (mCRP). The AP response was significantly and inversely associated with total cholesterol, HDL, low-density lipoprotein cholesterol, ApoA1, ApoB, lecithin cholesterol acyltransferase, CMPAase activity, and RCT index. After adjusting for the AP response, MDD diagnosis maintained significant independent associations with lower HDL-C, ApoA1, RCT, and higher ApoB/ApoA1 ratio. Multivariate (logistic) regression analyses confirmed that these lipid-inflammatory alterations strongly predict MDD diagnosis and clinical symptom severity. We found that around 81.5% of the MDD patients showed metabolic-inflammatory aberrations with a specificity of 82.1% and an area under the receiver operating characteristic (ROC) curve of 0.873. Lower ApoA1 emerged as a particularly robust protective biomarker, showing significant inverse relationships with affective and chronic fatigue severity scores. CONCLUSIONS:These findings illuminate the complex interplay between a smoldering inflammatory response and lipid metabolism in many patients with MDD.

ABSTRACT Background Major depressive disorder (MDD) is a prevalent mental illness with a significant disease burden. It is characterized by immune‐inflammatory dysregulation. Methods This ex vivo study assessed curcumin's immunomodulatory effects in 18 MDD patients and 18 healthy controls (HC). Whole blood samples underwent LPS‐ and PHA‐stimulation to evaluate immune sensitization with curcumin treatment at concentrations of 2, 20, and 200 ng/mL. Results MDD patients exhibited marked activation of the immune‐inflammatory response system (IRS), M1 macrophages, T helper (Th) 1, growth factors, and chemokine profiles, whereas M2, Th2, and the compensatory immunoregulatory system (CIRS) were less activated, confirming IRS sensitization in MDD. Partial regression analysis confirmed positive correlations between immune biomarkers (e.g., IL‐1β) and depression severity scores. In patients with MDD, curcumin selectively and significantly downregulated the overactivated IRS, M1, Th1, and chemokine profiles. Notably, curcumin significantly decreased pro‐inflammatory chemokines, such as CCL11, CXCL10, and CCL27, and exhibited inhibitory effects on key inflammatory factors, including TNF‐α. Although curcumin did not fully normalize the IRS profiles or significantly affect M2, Th2, or CIRS profiles, its specific inhibition of core inflammatory pathways clearly demonstrates its ability to selectively modulate aberrant immune responses in MDD. Paradoxically, in HC, curcumin showed mild immune‐stimulating effects. Conclusions These findings demonstrate that curcumin exerts selective anti‐inflammatory effects by effectively targeting and suppressing overactivated core inflammatory pathways (e.g., IRS/M1/Th1 and related chemokines) in MDD patients, thereby partially restoring immune homeostasis. This supports the potential role of curcumin as an adjunctive therapeutic strategy for MDD. However, as these findings are derived from an ex vivo model, further in vivo studies are required before clinical recommendations can be made.

Background and Aim Evidence proved that electroacupuncture (EA) combined with antidepressants can improve the antidepressant effectiveness for depressed patients. However, the clinical mechanisms of EA remain unclear. This study aimed to observe the mechanism of EA as an adjunct therapy to escitalopram oxalate (EO) on depressed patients. Experimental procedure This study was designed as a single-blinded, double-dummy randomized controlled trial. 61 participants were diagnosed with mild-to-moderate depression according to the International Classification of Diseases 10th Edition (ICD-10, F32) were randomly allocated to receive EA+EO placebo, EO+sham EA, or EA+EO for six weeks treatment. The clinical assessment including depression severity, quality of life (QOL) and clinical safety. Biological indicators of immune-inflammation, the brain-derived neurotrophic factor and glucocorticoid inducible genes in peripheral blood of participants were measured by using enzyme linked immunosorbent assay and real-time polymerase chain reaction respectively before and after treatment. Results and conclusion Three interventions improved the depression severity and QOL (P<0.05), and no inter-group difference was found in the 6th week (P>0.05). Anxiety psychic and somatic general symptoms in the EA+EO group were improved significantly than those of the other two groups (P<0.05). After six-week treatment of EA+EO, blood SGK1 mRNA, GILZ mRNA, and BDNF levels were increased significantly (P<0.05), and IL-6 levels were decreased significantly (P<0.05) in depressed patients. IL-6 change levels were positively correlated with the change of HAMD-24 score in patients who received EA+EO treatment (P<0.05). EA as an add-on therapy of EO probably enhanced antidepressant effectiveness through regulating multiple targets involved in blood BDNF, IL-6, and glucocorticoid-inducible genes GILZ mRNA and SGK-1 mRNA.

The Shidu Formula (SDF) ointment is a natural product-based medicine that has a long history of use in treating psoriasis. Compared to standard first-line clinical medications, SDF remedies present certain advantages, particularly in terms of causing minimal skin irritations. However, several challenges have limited their widespread applications. These include the sticky nature of SDF ointments, which can hinder drug penetration and lead to staining of the skin and clothing, and delayed onset of effects that often necessitates higher dosages. Therefore, the development of innovative topical solutions is highly required to deliver the complex components of SDF effectively. In this study, we developed an amphiphilic blended membrane of polycaprolactone (PCL) and polyethylene oxide (PEO) using electrospinning, successfully transforming the SDF ointment into nanofibrous meshes. We confirmed that it was feasible to incorporate a maximum of 5% SDF through morphological, physiological, and pharmacological assessment. The release profile of the principal active components verified that berberine chloride and gallnut were released in bursts. In vivo experiments further demonstrated the benefits and biocompatibility of the SDF-PCL/PEO membrane in the management of IMQ-induced psoriasis-like skin inflammation, as demonstrated by severity index scoring and pathological evaluations. Notably, converting the ointment into nanofibrous meshes addressed the typical challenges associated with conventional SDF ointment, resulting in significantly improved efficacy, short application times, controllable dosages, and reduced staining of the skin and clothes. This work provides a promising approach for transforming complex natural products into effective external treatment options for psoriasis.

BACKGROUND:Running exercise effectively ameliorates depressive symptoms in humans and depression-like behaviors in animals, but the underlying mechanisms remain unclear. Microglia-mediated neuroinflammation plays a major role in the development of depression. The medial prefrontal cortex (mPFC) is a key brain region involved in depression and is sensitive to physical activity. Whether the antidepressant effect of running exercise involves changes in mPFC microglia is not understood. METHODS:The animals were subjected to chronic unpredictable stress (CUS) intervention followed by treadmill running. The sucrose preference test and elevated plus maze test or tail suspension test were used for behavioral assessment of the animals. The number of microglia in the mPFC was quantified by immunohistochemistry and stereology. The density and morphology of microglia were analyzed via immunofluorescence staining combined with three-dimensional laser scanning techniques. The mRNA expressions of inflammatory cytokines in the mPFC were examined via quantitative real-time PCR. RESULTS:Running exercise effectively alleviated depressive-like behaviors in depression model animals. Running exercise reversed the increase in the number of microglia and the density of activated microglia in the mPFC of CUS animals. Running exercise effectively reversed the changes in microglia (reduced cell body area, total branch length and branch complexity) in the mPFC of CUS animals. Furthermore, running exercise regulated the gene expressions of pro-/antiinflammatory cytokines in the mPFC of CUS animals. CONCLUSIONS:Our results suggested that the antidepressant effects of running exercise may involve decreasing the number of activated microglia, reversing morphological changes in microglia in the mPFC, and reducing inflammatory responses.

Acupuncture, a Traditional Chinese Medicine (TCM) practice, aids in motor function recovery for stroke patients without pharmacological intervention. The central mechanisms of this effect remain unclear. In this study, the functional near-infrared spectroscopy (fNIRS) technique was used to investigate the effects of acupuncture treatment on the cerebral cortex. The fNIRS signals evoked during acupuncture treatment were collected from 30 healthy participants, and Massachusetts General Hospital Acupuncture Sensation Scale (MASS) were collected. The hemodynamic response and generalized linear model (GLM) were used to explore cortical activation. The functional connectivity (FC) was used to study the connectivity between regions of interest (ROIs). The results of the study indicate that the needles insertion (NI) enhanced the participants' needling sensation (MASS Index, t = 4.14, p < 0.001) and increased the oxygenated hemoglobin concentrations (F=0.98, p = 0.37) within the bilateral prefrontal cortex (PFC), the right pre-supplementary motor area (R-Pre-SMA), the right primary somatosensory cortex (R-PSC), and the right primary motor cortex (R-M1). The NI also resulted in significant cortical activation of bilateral PFC(p < 0.05) and weakened FC between the three main ROIs, (R-PSC and bilateral M1) and other ROIs significantly weakened (p < 0.05). This study reflect the cortical activation and functional connectivity of acupuncture for upper limb, which will ultimately help to explore the neural mechanism of acupuncture for upper limb motor dysfunction.

Perimenopausal depression (PMD) is a common condition during the female perimenopausal period. Tyrosol represents a promising neuroprotective agent. This study aims to determine if tyrosol alleviate PMD progression. A rat model of PMD was established using bilateral ovariectomy and chronic unpredictable mild stress. Behavioral tests showed that tyrosol alleviated the depressive-like behavior in PMD rats. Tyrosol increased sucrose preference in SPT and residence time in the central region of OFT, and reduced immobility time in FST of PMD rats. Apoptosis of neurons in the hippocampus of PMD rats was inhibited by tyrosol treatment, as evidenced by an increase in the protein expression of Bcl-2 and a decrease in the expression of Bax and cleaved caspase-3 in hippocampal tissue. Tyrosol treatment effectively reduced thyroid-stimulating hormone levels and elevated the levels of free triiodothyronine and free thyroxine in the serum of PMD rats. The levels of ROS and MDA were decreased, and the levels of GPX and SOD were increased in the hippocampal tissue of PMD rats by tyrosol treatment. In addition, tyrosol treatment promoted the levels of brain-derived neurotrophic factor (BDNF) and monoamine neurotransmitters (5-HT, DA, and NA) in the hippocampal tissue. In summary, tyrosol might ameliorate depression-like behavior in PMD rats by inhibiting hippocampal oxidative stress and damage and promoting monoamine neurotransmitter release, and restoration of thyroid function may also be involved.

Background: Idiopathic pulmonary fibrosis (IPF) is an irreversible lung disease for which there is a lack of effective and safe therapeutic drugs. 13-Methylpalmatine (13-Me-PLT) is an active compound from Coptis chinensis, and no study has yet been reported on its pharmacological effects in pulmonary fibrotic diseases. The group has previously demonstrated the antimyocardial fibrosis efficacy of 13-Me-PLT but its effect on pulmonary fibrosis and its potential mechanism has not yet been investigated. Purpose: The present research is designed to clarify the therapeutic potential and mechanism of action of 13-MePLT in IPF using a bleomycin (BLM)-induced mouse model of IPF. Methods: In vivo, mice were administrated with BLM to establish the IPF model, and IPF mice were treated with 13-Me-PLT (5, 10, and 20 mg/kg) and pirfenidone (PFD, 300 mg/kg) by gavage. In vitro, we employed TGF-(31 (10 ng/ml)-induced MRC5 cells, which were then treated with 13-Me-PLT (5, 10, 20 mu M) and PFD (500 mu M). High-throughput transcriptome sequencing, molecular dynamics simulations, molecular docking and Surface plasmon resonance (SPR) were employed to elucidate the underlying mechanisms of 13-Me-PLT in mitigating IPF. Result: In vivo experiments showed that 13-Me-PLT significantly ameliorated BLM-induced lung fibrosis in mice. In vitro studies, 13-Me-PLT showed good antifibrotic potential by inhibiting fibroblast differentiation. Transcriptomic analysis of mouse lung tissues identified ITGA5 and TGF-(3/Smad signaling pathways as key targets for the antifibrotic effects of 13-Me-PLT. Molecular docking and kinetic analyses further supported these findings. Functional studies involving ITGA5 silencing and overexpression confirmed that 13-Me-PLT down-regulated ITGA5 expression and inhibited the activation of the TGF-(3/Smad signaling pathway, confirming its mechanism of action. Conclusion: To our best knowledge, these results provide the first insight that 13-Me-PLT is protective against BLM-induced IPF in mice. Unlike existing antifibrotic drugs, 13-Me-PLT specifically targets the ITGA5/TGF(3/Smad signaling pathway, offering a novel and potentially more effective therapeutic approach. This study not only validates the antifibrotic efficacy of 13-Me-PLT but also elucidates its unique mechanism of action, these findings may provide an opportunity to develop new drugs to treat IPF.

Purpose: Far-infrared ray (FIR) is an electromagnetic wave known to impart health benefits against various pathophysiological conditions, including diabetes mellitus, renocardiovascular disorders, stress, and depression, among others. However, the precise impact of FIR on major depressive disorder (MDD) and the underlying molecular mechanisms remain unclear. Here, we aimed to investigate the effects and elucidate the molecular mechanisms of FIR on depression-like behavior in mice. Methods: A mouse model of depression was established using chronic restraint stress (CRS). Behavioral tests were performed to assess alterations in depression-like behaviors. Biochemical methods were employed to measure the levels of IL-1β, IL-6, TNF-α, S100β, IL-17, melatonin (MT), 5-hydroxytryptamine (5-HT), glutathione (GSH), malondialdehyde (MDA), brain-derived neurotrophic factor (BDNF), and corticosterone (CORT) in mice serum. Similarly, the levels of IL-1β, IL-6, TNF-α, S100β, IL-17, and MT in mice brains were measured using biochemical methods. Hematoxylin-eosin and Nissl staining were utilized to detect morphological changes in the mice hippocampus. In addition, the structure and mitochondrial morphology of hippocampal neurons and microglia were studied using transmission electron microscopy (TEM). Results: The results of behavioral tests revealed that FIR mitigated the depression-like behaviors induced by CRS. FIR also reversed the levels of IL-1β, IL-6, TNF-α, and related cytokines in the periphery and brain. The results of hematoxylin-eosin and Nissl staining showed that FIR improved the damage of mice's hippocampus. Additionally, TEM revealed that FIR alleviated the damage of CRS to hippocampal neurons and microglia. Conclusion: Our findings suggest that FIR can ameliorate depression-like behavior induced by CRS in mice. FIR can reverse the levels of related cytokines in the periphery and brain, and alleviate damage to neurons and microglia, which may constitute its underlying molecular mechanism.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by inflammation, with current Western treatments focusing on symptom relief and disease progression control through antiinflammatory, analgesic, and immunosuppressive drugs. However, these therapies have significant side effects and limited long-term efficacy. Therefore, novel treatment options are urgently needed. Lonicerae japonicae Caulis (LJC), a traditional Chinese medicine, has alleviated RA symptoms such as joint pain and swelling. Despite its widespread use, the underlying mechanisms of its therapeutic effects remain poorly understood. This research aimed to uncover the mechanisms by which LJC intervenes in RA, using transcriptomics and energy metabolomics. RA was induced in rats via Type II collagen and incomplete adjuvant. LJC's effects were assessed through joint swelling, TNF-α levels, and histopathology. Mechanisms were analyzed using transcriptomics and metabolomics. The role of chlorogenic acid (CGA) was verified in LPS-induced RAW264.7 cells. LJC reduced joint swelling and TNF-α levels and inhibited synoviocyte proliferation and angiogenesis. Transcriptomics revealed LJC modulated RA pathways and inflammation. Metabolomics identified cis-aconitic acid as a key metabolite in energy metabolism. CGA was confirmed as the primary active component. LJC alleviates RA by inhibiting inflammation and modulating energy metabolism through multiple pathways.

Background: Bipolar disorder is a very common, often misdiagnosed mental disorder strongly associated with comorbidity, disability, and premature mortality. Bipolar depression (i.e., depressive episode in bipolar disorder) is poorly responsive to available treatments. Acupuncture at five Zang-shu and Ge-shu, a prescription from Dr. Leting Wang, is a popular therapy for depression in China. Its effectiveness and safety for bipolar depression is yet to be verified by clinical study. Methods/design: The study is a single-center, prospective, randomized controlled trial involving 72 patients diagnosed with bipolar depression. Participants will be randomized either to the study group or the control group in a 1:1 ratio. All participants will receive mood stabilizer therapy. In addition, the study group will receive acupuncture therapy at five Zang-shu and Ge-shu, three times per week. The control group will orally take the antidepressant bupropion. Observation and intervention will last for 8 consecutive weeks. Outcome measurements include Hamilton Depression Rating Scale-17 (HAMD-17), Hamilton Anxiety Rating Scale (HAMA), Clinical Global Impression Scale (CGI), Young Manic Rating Scale (YMRS), Treatment Emergent Symptom Scale (TESS), serum levels of anti-inflammatory cytokines (IL-4, IL-10, TGF-β), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α), brain-derived neurotrophic factor (BDNF) and C-Reactive Protein (CRP). Assessments will be conducted at baseline, 1st, 2nd, 4th and 8th week after randomization. Safety assessments will be performed throughout the study. Discussion: The results of this study are expected to verify the effectiveness and safety of acupuncture at five Zang-shu and Ge-shu for bipolar depression, and explore its therapeutic mechanisms from the point of anti- inflammation.

Objective: To explore the feasibility of remotely obtaining complex information on traditional Chinese medicine (TCM) pulse conditions through voice signals. Methods: We used multi-label pulse conditions as the entry point and modeled and analyzed TCM pulse diagnosis by combining voice analysis and machine learning. Audio features were extracted from voice recordings in the TCM pulse condition dataset. The obtained features were combined with information from tongue and facial diagnoses. A multi-label pulse condition voice classification DNN model was built using 10-fold cross-validation, and the modeling methods were validated using publicly available datasets. Results: The analysis showed that the proposed method achieved an accuracy of 92.59% on the public dataset. The accuracies of the three single-label pulse manifestation models in the test set were 94.27%, 96.35%, and 95.39%. The absolute accuracy of the multi-label model was 92.74%. Conclusion: Voice data analysis may serve as a remote adjunct to the TCM diagnostic method for pulse condition assessment.

The widespread use of chlorine-based disinfectants in drinking water treatment has led to the proliferation of chlorine-resistant bacteria and the risk of disinfection byproducts (DBPs), posing a serious threat to public health. This study aims to explore the effectiveness and potential applications of epigallocatechin gallate (EGCG) against chlorine-resistant Bacillus and its spores in water, providing new insights for the control of chlorine-resistant bacteria and improving the biological stability of distribution systems. The inactivation effects of EGCG on Bacillus subtilis (B. subtilis) and its spores were investigated using transmission electron microscopy, ATP measurement, and transcriptome sequencing analysis to determine changes in surface structure, energy metabolism, and gene expression levels, thereby elucidating the inactivation mechanism. The results demonstrate the potential application of EGCG in continuously inhibiting chlorine-resistant B. subtilis in water, effectively improving the biological stability of the distribution system. However, EGCG is not suitable for treating raw water with high spore content and is more suitable as a supplementary disinfectant for processes with strong spore removal capabilities, such as ozone, ultraviolet, or ultrafiltration. EGCG exhibits a disruptive effect on the morphological structure and energy metabolism of B. subtilis and suppresses the synthesis of substances, energy metabolism, and normal operation of the antioxidant system by inhibiting the expression of multiple genes, thereby achieving the inactivation of B. subtilis.

Purpose: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. Study design and Methods: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sitto-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. Results: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. Conclusions: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging.

Background From 2004 onwards, the Chinese government has freely offered complimentary Chinese herbal medicine (CHM) to Chinese HIV/AIDS patients, alongside the prescribed first line therapy of highly active antiretroviral therapy (HAART). Thus, we aimed to explore the effectiveness and safety of CHM for patients with HIV/AIDS. Methods The data from the Guangxi pilot database and antiviral treatment sites database have been respectively developed into two datasets in this prospective cohort real-world study, the CHM combined HAART group (the integrated group) and the HAART group. A 1:1 propensity score matching (PSM) was performed and the longitudinal data were analyzed using a generalized estimating equation (GEE) model with an autocorrelation matrix and log link function attached to the Gamma distribution. Results A final sample of 629 patients, 455 and 174 in the integrated group and HAART group respectively, were obtained from the full dataset. As covariates for PSM, gender, age, baseline CD4+ and CD4+/ CD8+ were assessed based on the results of the logistic regression analyses. Following PSM, 166 pairs from the full dataset were matched successfully, with 98 pairs in the baseline CD4+ > 200 subgroup, and 55 pairs in the baseline CD4+ ≤ 200 subgroup. In the full dataset, HAART group achieved higher CD4+ count (OR = 1.119, 95%CI [1.018, 1.230]) and CD4+/CD8+ ratio (OR = 1.168, 95%CI [1.045, 1.305]) than the integrated group, so did in the CD4+ > 200 subgroup. For the CD4+ ≤ 200 subgroup, the CD4+ (OR = 0.825, 95%CI [0.694, 0.980]) and CD4+/CD8+ (OR = 0.826, 95%CI [0.684, 0.997]) of the integrated group were higher than those of the HAART group. The safety outcomes showed that there were no significant differences in BUN, ALT and AST levels between the groups but Cr showed significantly higher levels in HAART groups of all three datasets. Conclusions Compared to HAART alone, CHMs combined with HAART had better effects in improving the immune function of HIV/AIDS in patients with baseline CD4+ count ≤ 200. The results of the two subgroups are in opposite directions, and chance does not explain the apparent subgroup effect. A study with larger sample size and longer follow-up period is warranted in order to increase study credibility.