AIM:Alzheimer's Disease (AD) is a neurodegenerative condition with poorly understood mechanisms and few effective treatments. β-asarone has shown potential in AD management, though its molecular actions require further clarification. This study investigates the mechanisms through which β-asarone exerts its effects using both animal and cellular models. METHODS:In vivo, the 3×Tg-AD mice were administered β-asarone for 8 weeks. Learning and memory abilities were assessed via the Morris water maze and step-down tests. Histomorphological examination, immunofluorescence, immunohistochemistry, ELISA, transmission electron microscopy, and Western blotting were employed to detect pathological changes, neuroinflammation, and protein expression of relevant signaling pathway molecules. In vitro, Aβ was used to culture BV-2 cells to mimic the brain microenvironment in Alzheimer's disease; changes in neuroinflammation, autophagy, and NLRP3 inflammasome-related proteins were observed after treatment with β-asarone. RESULTS:The administration of β-asarone resulted in enhanced cognitive performance in 3×Tg-AD mice, alongside a reduction in microglial apoptosis induced by Aβ. Additionally, β-asarone diminished the accumulation of Aβ and phosphorylated Tau, ultimately supporting neuronal survival. In both the hippocampal tissue and BV-2 cell models, treatment with β-asarone led to a downregulation of neuroinflammatory markers and modulation of autophagy-related proteins (Beclin-1, P62, ATG5, LC3-II/I), while concurrently suppressing components of the NLRP3 inflammasome (NLRP3, ASC, Caspase-1, cleaved Caspase-1). Notably, the autophagy inhibitor 3-MA counteracted the inhibitory effects of β-asarone on NLRP3 activation. CONCLUSION:β-Asarone attenuates AD-related neuroinflammation by activating autophagy to inhibit NLRP3 inflammasome assembly.

Abstract Cancer remains a significant global health threat. The tumor microenvironment (TME) is a sophisticated ecological niche that exerts a pivotal effect on treatment outcomes. Among the diverse components composing the TME, the intratumoral microbiota (IM) has become a research focus, which can regulate tumor initiation, progression, and therapeutic response. The link between cancer and microorganisms dates back 4000 years. Advanced sequencing technologies have revealed that the unique microbial communities within tumors serve a dual function: directly modulating tumor cell biology via metabolic processes and shaping TME immunity through interactions with immune and matrix components. Their metabolites act as mediators either inducing immunosuppression via immune metabolic reprogramming or triggering systemic immunity through pattern recognition receptors. Consequently, IM imbalances may contribute to immune evasion and therapeutic resistance. This article addresses immunotherapy resistance and treatment failure, systematically exploring the origins and detection methods of IM, elucidating its regulatory mechanisms within the TME, examining its impact on immunotherapy efficacy, assessing the utility of IM in diagnostic biomarker applications, and discussing the technical challenges and a roadmap for further inquiry, directed toward providing a comprehensive framework to advance precision immunotherapy in cancer treatment.

Neuroinflammation, driven by dysregulated microglial polarization, is a hallmark of Alzheimer’s disease (AD). Recently, the triggering receptor expressed on myeloid cells 2 (TREM2), a key regulator of microglial function, has emerged as a promising therapeutic target for AD. This study aimed to investigate the therapeutic potential and mechanism of action of the natural compound β-asarone in AD models. Our results demonstrate that β-asarone significantly improved cognitive function, reduced hippocampal neuronal damage, and decreased both Aβ deposition and Tau hyperphosphorylation in 3×Tg-AD mice. Mechanistically, β-asarone upregulated TREM2 expression, activated the PI3K/AKT pathway, and inhibited GSK3β activity, thereby promoting the polarization of microglia from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype and alleviating neuroinflammation. This study is the first to elucidate that β-asarone ameliorates AD pathology by modulating microglial polarization via the TREM2/PI3K/AKT/GSK3β signaling axis, providing experimental evidence supporting its potential as an immunomodulatory therapeutic agent for AD.

PURPOSE:The aim of this study was to investigate the protective effect of Free and Easy Wanderer (FAEW) on the avoidance behavior induced by feeding Heat-Killed Escherichia coli, and to elucidate the underlying mechanisms. METHODS:Initially, the effects of FAEW on avoidance behavior, survival, neuroendocrine signaling gene expression, and intestinal bloating were examined. The impact of FAEW on gut-germline-neural signaling was assessed by monitoring H4K8ac expression and the avoidance behavior of par-5 RNAi animals and glp-1(e2141) mutants. RNA-sequencing was conducted to analyze potential signaling pathways. Finally, avoidance behavior was examined using daf-16(mu86) mutants and the rescued animals. RESULTS:FAEW delayed avoidance behavior. FAEW significantly downregulated gene expression in the neuroendocrine signaling pathway and alleviated intestinal bloating of C. elegans. The levels of H4K8ac and par-5 in the germline decreased significantly with FAEW's treatment, and FAEW failed to affect the avoidance behavior of par-5 RNAi animals and glp-1(e2141) mutants. FAEW's effect on avoidance behavior diminished in daf-16(mu86) mutants but was restored in daf-16 rescued animals. FAEW has been observed to restore daf-16 levels. CONCLUSION:FAEW protects against avoidance behavior of C. elegans through downregulating H4K8ac protein expression and activating DAF-16. This study provides crucial experimental evidence supporting FAEW as a promising candidate for protecting against avoidance behavior associated with PTSD.

BACKGROUND:Alcohol-related liver disease (ALD) has become an increasingly serious global health issue. In recent years, growing evidence has highlighted the restoration of liver regenerative capacity as an effective therapeutic strategy for improving ALD. Previous studies have demonstrated the protective effect of dihydromyricetin (DMY) in alcohol-induced liver injury, but its pharmacological role in ALD-related liver regeneration impairment remains poorly understood. OBJECTIVE:This study aims to explore the therapeutic potential and molecular mechanisms of DMY in the context of liver regeneration impairment in ALD. METHODS:The classic Lieber-DeCarli alcohol liquid diet was used to establish an ALD model in vivo. DMY (75 and 150 mg/kg/day) and silybin (200 mg/kg) were administered for 7 weeks to assess the hepatoprotective effects of DMY. First, biochemical markers and liver histopathology were used to evaluate liver inflammation and steatosis in ALD mice. Second, we explored the potential molecular mechanisms by which DMY improves ALD through serum untargeted metabolomics, hepatic transcriptomics, and single-cell sequencing data. Furthermore, in vivo and in vitro experiments, combined with Western blotting, dual-luciferase reporter assays, and immunofluorescence, were conducted to elucidate the protective mechanisms underlying DMY's effects on ALD. RESULTS:In vivo studies showed that DMY significantly ameliorated ALT/AST abnormalities, liver inflammation, and steatosis in ALD mice. Multi-omics and bioinformatics analyses revealed that DMY may exert its anti-ALD effects by regulating the miR-155-5p/SIRT1/VDAC1 pathway, thereby mitigating cellular senescence. Notably, knockdown of miR-155 provided partial protection against ethanol-induced liver damage. Additionally, clinical ALD samples and in vivo and in vitro experiments further confirmed that excessive alcohol exposure induces the production of miR-155-5p in liver Kupffer cells. miR-155-5p targets and inhibits SIRT1, promoting the expression of mitochondrial VDAC1, leading to mitochondrial DNA leakage, thereby accelerating hepatocyte senescence and inflammation. However, DMY improved the disruption of the miR-155-5p/SIRT1/VDAC1 pathway and hepatocyte senescence, thereby restoring liver regenerative function and exerting anti-ALD effects. CONCLUSION:In this study, we provide the first evidence that DMY improves liver inflammation and cellular senescence by regulating the miR-155-5p/SIRT1/VDAC1 positive feedback loop, promoting liver regeneration to improve ALD. In summary, our work provides important research evidence and theoretical support for DMY as a promising candidate drug for the prevention and treatment of ALD.

BACKGROUND:Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases with undefined pathogenesis and unsatisfactory therapeutic options. Shenqi Wan (SQW), a traditional Chinese medicinal compound, has demonstrated certain preventive and therapeutic effects on COPD. However, the underlying molecular mechanisms remain incompletely understood. In this study, we used weighted gene co-expression network analysis (WGCNA) and machine learning to identify biomarkers for COPD, combined with network pharmacology and experimental validation to evaluate how SQW reduces airway inflammation in COPD. METHODS:Targets of SQW in treating COPD and its network regulation mechanism were predicted via network pharmacology. Meanwhile, potential biomarkers were predicted using WGCNA and machine learning algorithms and validated in COPD patients. The relationship between the core pathway and key target was analyzed by ingenuity pathway analysis (IPA) to reveal the regulatory mechanism of SQW. We evaluated the efficacy of SQW treatment in LPS/MS-induced COPD mice by evaluating lung function, histopathological parameters, and levels of inflammatory markers and oxidative stress. The distribution and expression of OPN/CD44/PI3K loop-related proteins were examined through immunofluorescence staining and Western Blotting. In vitro, we added LPS to BEAS-2B cells to mimic the inflammatory microenvironment and transfected the cells with OPN overexpression plasmid to observe the improvement induced by SQW. RESULTS:GO and KEGG analyses demonstrated that SQW inhibited inflammation and oxidative stress via the PI3K/Akt pathway, thereby improving COPD. Machine learning algorithms identified OPN as a potential biomarker, with elevated expression observed in the lung tissue of COPD patients. IPA indicated that OPN may modulate the CD44-mediated activation of the PI3K/AKT pathway, forming a positive feedback regulatory mechanism. SQW ameliorated lung function and pathological injury in mice; further, it reduced inflammation, oxidative stress, and OPN/CD44/PI3K positive feedback loop-related protein expression in both mice and cells. After OPN overexpression, the levels of inflammatory factors and ROS were significantly increased, and the OPN/CD44/PI3K signal was further activated, weakening the ameliorative effect of the SQW drug-containing serum. CONCLUSION:Overall, SQW contributed to ameliorating COPD by reducing airway inflammation and oxidative stress through inhibiting the OPN/CD44/PI3K positive feedback loop.

BACKGROUND:Avoidance behavior is one of the core features of anxiety and related in-depth study can help to reveal the biological basis of these disorders. In recent years, traditional Chinese medicine has incorporated Shen Qi pills to treat neuropsychiatric disorders, such as depression and post-traumatic stress, and has achieved significant therapeutic effects. However, its specific mechanism of action is still unclear. PURPOSE:The aim of this study was to link the avoidance phenotype to psychiatric disorders by utilizing the Caenorhabditis elegans as a biological model, revealing the potential common mechanisms underlying the treatment of these disorders with Shen Qi pills. METHODS:Avoidance behavior and immunity of C. elegans as a phenotypic entry point to explore the molecular mechanisms by which Shen Qi pills affects avoidance behavior with the help of pmk-1 and daf-16 mutants and RNA interference techniques. RESULTS:We found that the intervention of Shen Qi pills can delay the avoidance behavior of C. elegans to P. aeruginosa, improve the immunity level, and reduce the up-regulation of pmk-1 and daf-16 genes induced by P. aeruginosa. Shen Qi pills did not improve the immunity of pmk-1 mutant but could still enhance the immunity of daf-16 mutant. After daf-16 knockout, Shen Qi pills could not delay its avoidance behavior, which was consistent with the results shown in the neuron-specific silencing of daf-16 C. elegans. CONCLUSION:These findings reveal the conclusion that Shen Qi pills regulate the avoidance behavior of C. elegans induced by P. aeruginosa via PMK-1 and DAF-16, with the latter acting directly on neurons independent of immune pathways.

ETHNOPHARMACOLOGICAL RELEVANCE:Guifu Dihuang Pills (GFDHP), a classical Chinese herbal formula originally recorded in the Synopsis of the Golden Chamber (Jingui Yaolüe), significantly ameliorate cognitive dysfunction in patients with Alzheimer's disease (AD). However, the precise molecular mechanisms underlying its therapeutic effects, particularly those involving the regulation of cerebral insulin resistance (IR), are not yet fully elucidated. AIM OF THE STUDY:This study systematically investigated the neuroprotective mechanism of the traditional Chinese medicine (TCM) compound GFDHP in alleviating AD by integrating RNA-seq transcriptomics, surface plasmon resonance (SPR) analysis, and bioinformatic analysis. The aim was to clarify its key targets and signaling pathways involved in the modulation of cerebral IR by in vitro and in vivo experiments. METHODS:The chemical components of GFDHP were characterized using ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). An AD model with cerebral IR was established by an intracerebroventricular streptozotocin (ICV-STZ) injection. Cognitive function was assessed using the Morris water maze (MWM) test, while hippocampal damage was evaluated by histological staining. The insulin level in hippocampal tissues was quantified using enzyme-linked immunosorbent assay (ELISA). AD-related proteins were analyzed using immunohistochemistry and Western blot. Integrated transcriptome sequencing, AlphaFold3 prediction, and SPR analysis confirmed the interaction between neuronal cell adhesion molecule (NrCAM) and epidermal growth factor receptor (EGFR). In vitro experiments were performed using HT22 cells treated with dexamethasone (DXM) to induce an IR model, followed by evaluation of IR and AD-related markers. Lentivirus-mediated shRNA knockdown of NrCAM was performed to systematically examine its regulatory effect on the EGFR/PI3K/Akt signaling pathway and GFDHP's therapeutic intervention. RESULTS:GFDHP significantly attenuated ICV-STZ-induced IR and AD-related neuropathological alterations. SPR analysis further revealed that NrCAM mediated the neuroprotective effect through the specific binding to EGFR, thereby activating the downstream PI3K/Akt signaling cascade. NrCAM silencing not only exacerbated both IR and AD pathology but also suppressed the EGFR/PI3K/Akt pathway and reduced the therapeutic effect of GFDHP. CONCLUSIONS:This study demonstrated that GFDHP alleviated IR by upregulating NrCAM expression and subsequently activating the EGFR/PI3K/Akt signaling pathway, thereby ameliorating AD. This is the first report identifying NrCAM as the key molecular target mediating the neuroprotective effect of this herbal formulation, providing a novel therapeutic strategy for AD treatment.

For over a millennium, the leaves of Ampelopsis grossedentata (Hand.-Mazz.) W. T. Wang, commonly known as vine tea, have been revered as a popular tea and traditional herbal remedy, possessing antioxidant, anti-inflammatory, hepatoprotective, and antiviral properties. In recent years, the incidence of alcohol-related liver injury has been on the rise, imposing a significant public health burden worldwide. Previous studies have indicated that extracts of vine tea (AGE) can ameliorate alcoholic liver disease (ALD), yet the pharmacological mechanisms underlying this effect remain poorly understood. In this study, we first employed UPLC-Q-TOF-MS to analyze the chemical constituents of AGE. Subsequently, an ALD model was established in mice fed with Lieber-DeCarli diet, and the hepatoprotective benefits of AGE were assessed by measuring biochemical indicators and hepatic pathological changes. Moreover, a suite of bioinformatics tools, including transcriptomics, weighted gene co-expression network analysis, and single-cell data mining, were utilized to reveal that the YTHDF2/PGC-1α/SIRT3 signaling axis may be the potential mechanism by which AGE exerts its anti-ALD effects. Additionally, Western blotting and immunofluorescence staining techniques were employed to further substantiate the aforementioned mechanism. Our findings demonstrate that administration of vine tea significantly alleviated chronic ethanol-induced hepatic lipid accumulation, oxidative stress, and inflammation. Notably, knockdown of YTHDF2 partially protected the liver from ethanol-induced injury. Mechanistically, bioinformatics analysis and in vitro and in vivo experiments identified YTHDF2 as a key pharmacological target of AGE in treating ALD, acting through the downstream PGC-1α/SIRT3 pathway. In summary, in this study, we provide the first evidence that AGE mitigates ethanol-induced liver injury by inhibiting YTHDF2 and enhancing the expression of PGC-1α and SIRT3. Vine tea, as a tea food with unique medicinal value, shows significant potential and value in the treatment of ALD.

BACKGROUND:Renal fibrosis is a common terminal pathway for various CKDs. Shenqi Wan (SQW) can reduce the development of renal fibrosis and may be associated with aquaporin 1 (AQP1) as discovered previously. PURPOSE:The mechanism of SQW in mitigating the progression of renal fibrosis and alleviating CKD was analyzed. METHODS:UPLC-Q-TOF-MS was used to identify the components of SQW. Clinical samples were used to validate AQP1 expression. Adenine-induced and AQP1-/- mice were used for in vivo experiments, whereas AQP1-knockdown HK-2 cells were used for in vitro experiments. Transcriptomic sequencing was used to analyze the molecular alterations of AQP1 and its associated biomarkers and to determine changes in renal tissues and cells. RESULTS:SQW significantly decreased elevated total urine protein and serum creatinine levels in wild-type mice with CKD and alleviated kidney damage and fibrosis. Renal dysfunction and cellular senescence were significantly exacerbated in AQP1 knockout mice. SQW increased AQP1 expression and exerted a protective effect in adenine-induced CKD in wide-type mice. Furthermore, AQP1 expression was decreased markedly in kidney biopsies of patients with CKD compared to healthy subjects. AQP1 mediated the activation of TGF-β1, which was significantly elevated in kidney tissues in CKD. SQW administration did not significantly alleviate renal dysfunction and cellular senescence in adenine-induced AQP1-/- mice in vivo and AQP1-knockdown human renal proximal tubular HK-2 cells in vitro, indicating AQP1 as a key target for SQW in alleviating CKD. CONCLUSION:SQW alleviated cellular senescence and mitochondrial dysfunction by upregulating AQP1 and targeting the AQP1/TGF-β1/ITPR1 axis, thereby mitigating CKD.

Astragali Radix is renowned for its dual use in medicine and food. This study presented a comprehensive approach that combines ultra-high performance liquid chromatography/ion mobility-quadrupole time-of-flight mass spectrometry, in-house library matching, fragment ion identification, molecular networking and collision cross section prediction to assess Astragali Radix quality. Based on this approach, 130 compounds were successfully characterised, categorised into 38 saponins, 68 flavonoids, 10 amino acids, 5 organic acids, and others. Additionally, 8 pairs of isomers were verified based on collision cross section measurements. Furthermore, Astragali Radix produced in the Gansu, Shanxi and Jilin provinces could be successfully discriminated using PLS-DA and OPLS-DA models. Twenty differential metabolites were identified including 8 flavonoids and 12 saponins such as astragaloside II, neoastragaloside I, astragaloside VII, astragaloside VI, soyasaponin I, calycosin-7-O- glucoside, formononetin-7-O-glucoside-6"-O-acetate, and ononin, which could be used as potential markers.

BACKGROUND:Depression is characterized by low mood, cognitive slowing and a tendency to self-harm, and has a complex etiology involving abnormalities in neuromodulation (e.g., monoamine transmitter imbalance and reduced neuroplasticity). Gut-brain axis studies have shown that dysregulation of gut flora can trigger neuroinflammation and impair glial cell function, leading to depression. Modulation of flora-glial cell interactions and their pharmacological mechanisms is key to treatment. PURPOSE:This review discusses the new discovery of the interaction mechanism between glial cells and gut microflora in depression models, providing new targets and directions for the treatment of TCM in depression. Further bridging the gap in current research on the gut-brain axis in depression. METHOD:Literature was searched, analyzed, and collected using PubMed, Web of Science, and China National Knowledge Infrastructure. The search terms used were " gut-brain axis ", " neuroinflammation ", " depression ", " glial cells ", " Gut microbiota "," TCM ", etc. Several combinations of these keywords were used. Studies using models of depression were used. RESULTS:During the literature screening process, a total of 1685 records were initially retrieved from databases. After removing duplicates (1068) and other ineligible records (200), 417 articles underwent title and abstract screening, with 134 excluded. Further full-text assessment of 283 articles led to the inclusion of 149 new studies. Reasons for exclusion included mismatched outcomes (8), ineligible experimental models (12), among others. Combined with 14 previously included studies, the final review comprised 163 articles (See Figure 1). The dialog mechanism between gut microflora and glial cells plays an important role in the pathogenesis of depression. In addition, there are a variety of herbal active ingredients and herbal formulas that can significantly affect the composition of the gut flora and glial cell activation in depression models, and consequently, there is significant antidepressant potential. CONCLUSION:Intestinal flora metabolites modulate glial cell activation, and the release of inflammatory factors by glial cells alters intestinal flora composition, both phenomena are contributory to depressive pathogenesis. In addition, we found that a variety of TCMs can improve depression based on this mechanism, providing new perspectives for clinical diagnosis and treatment of depression.

Chronic kidney disease (CKD), defined by a glomerular filtration rate (GFR) below 60 mL/min/1.73 m2 for over 3 months, is a significant global health concern, often progressing to end-stage renal disease (ESRD). Oligoasthenospermia (OA), characterized by reduced sperm count or quality, affects male fertility, contributing to infertility in approximately 15% of couples worldwide. Both conditions share features of yang deficiency, including fatigue, cold intolerance, and weakness. Shenqi Pill (SQP), a Traditional Chinese Medicine (TCM) formula, replenishes kidney yang and demonstrates efficacy in treating yang deficiency-related diseases such as CKD and OA. However, the molecular mechanisms underlying its therapeutic effects remain unclear. This study combined ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), network pharmacology, and machine learning to identify SQP's active compounds and potential targets. A CKD model was induced in C57BL/6 mice via adenine administration, followed by SQP treatment (0.8 or 1.6 g/kg/day) for 50 days. Renal function, histopathology, and molecular pathways were evaluated. Additionally, in vitro assays were performed to validate SQP's effects on OA using GC-1spg spermatogonia. 41 compounds in SQP were identified. Network pharmacology suggested SQP ameliorates CKD and OA by modulating cellular senescence, with SIRT1, RELA, and NFKB1 as key targets. In vivo, SQP improved renal dysfunction, reduced glomerular atrophy, tubular dilation, and collagen deposition, with higher doses demonstrating superior efficacy. RNA-Seq analysis highlighted SQP's regulation of the SIRT1/NF-κB pathway and cellular senescence. ELISA, β-galactosidase staining, and Western blotting confirmed reduced senescence-associated secretory phenotype (SASP) release and normalization of SIRT1/NF-κB1 activity. In vitro, SQP-containing serum alleviated cellular senescence in GC-1spg spermatogonia by mitigating SIRT1/NF-κB1 disruptions without cytotoxicity. SQP demonstrates therapeutic potential for CKD and OA by targeting the SIRT1/NF-κB signaling pathway, providing evidence for its clinical application in treating kidney-yang deficiency-related diseases.

Alcohol-related liver disease (ALD) is a major cause of morbidity and mortality worldwide. It encompasses conditions such as fatty liver, alcoholic hepatitis, chronic hepatitis with liver fibrosis or cirrhosis, and hepatocellular carcinoma. Numerous recent studies have demonstrated the critical role of oxidative stress, abnormal lipid metabolism, endoplasmic reticulum stress, various forms of cell death (including apoptosis, necroptosis, and ferroptosis), intestinal microbiota dysbiosis, liver immune response, cell autophagy, and epigenetic abnormalities in the pathogenesis of ALD. Currently, abstinence, corticosteroids, and nutritional therapy are the traditional therapeutic interventions for ALD. Emerging therapies for ALD mainly include the blockade of inflammatory pathways, the promotion of liver regeneration, and the restoration of normal microbiota. Summarizing the advances in animal models of ALD will facilitate a more systematic investigation of the pathogenesis of ALD and the exploration of therapeutic targets. This review summarizes the latest insight into the pathogenesis and molecular mechanisms of ALD, as well as the pros and cons of ALD rodent models, providing a basis for further research on therapeutic strategies for ALD.

Chronic myelogenous leukemia (CML) is a malignant tumor of the blood system, so far there is no effective cure. Imatinib (IM), as the first-line drug for the clinical targeted treatment of CML, has some limiting factors such as drug resistance and relapse, and drug resistance has also emerged in combination with other drugs. At present, traditional Chinese medicine combined with targeted drugs in the treatment of tumor is a research hotspot. The total saponin of L. (TSRP) has an effective anti-tumor activity. Our previous in vitro experiments showed that TSRP can effectively inhibit the proliferation and promote apoptosis of CML cells K562, suggesting that TSRP can effectively reverse the drug resistance of IM, but the mechanism of drug resistance remains unclear. Studies have shown that the PI3K/AKT pathway is the main activation pathway of IM secondary resistance, and is considered to be an innovative therapeutic strategy for targeted cancer treatment, which may be an important mechanism of IM resistance. This project aims to reveal the possible mechanism of TSRP reversing IM resistance through PI3K/AKT signaling pathway through both in vitro and in vivo experiments, providing experimental basis for TSRP combined with IM treatment of CML.

Icariin (ICA), a natural flavonoid glucoside from traditional Chinese medicine, possesses various pharmacological properties such as anti-inflammatory, anti-aging, and neuroprotective effects. Recent studies suggest its potential in treating Alzheimer ' s disease (AD). However, the exact mechanisms of how ICA modulates neuroinflammation in AD remain unclear. In this study, oral ICA administration improved cognitive function in mice, decreasing escape latency in behavioral tests and altering protein levels related to AD pathology, including boosting acetylcholine and reducing p-tau/tau and acetylcholinesterase. Additionally, in 3 x Tg -AD mice, ICA therapy inhibited microglia and astrocyte activation and reduced inflammatory cytokines (IL-1 beta , TNF- alpha, IL -6) at the protein level. RNA-seq analysis revealed decreased expression of Nrxn3 , Meg3 , and Malat1 genes in 3 x Tg -AD animals treated with ICA. Furthermore, ICA activated the Akt/GSK-3 beta signaling pathway, known for its role in neuroinflammation, suggesting a potential mechanism by which ICA suppresses inflammation. This study proposes Meg3 and Malat1 lncRNA as therapeutic targets against AD, offering a novel approach for combating neuroinflammation in AD through the inhibition of the Akt/GSK-3 beta pathway.

We delve into the critical role of the gut microbiota and its metabolites in the pathogenesis and progression of hepatobiliary and pancreatic (HBP) cancers, illuminating an urgent need for breakthroughs in diagnostic and therapeutic strategies. Given the high mortality rates associated with HBP cancers, which are attributed to aggressive recurrence, metastasis, and poor responses to chemotherapy, exploring microbiome research presents a promising frontier. This research highlights how microbial metabolites, including secondary bile acids, short-chain fatty acids, and lipopolysaccharides, crucially influence cancer cell behaviors such as proliferation, apoptosis, and immune evasion, significantly contributing to the oncogenesis and progression of HBP cancers. By integrating the latest findings, we discuss the association of microbial alterations with HBP cancers, key metabolites, and their implications, and how metabolomics and microbiomics can enhance diagnostic precision. Furthermore, the paper explores strategies for targeted therapies through microbiome metabolomics, including the direct therapeutic effects of microbiome metabolites and potential synergistic effects on conventional therapies. We also recognize that the field of microbial metabolites for the diagnosis and treatment of tumors still has a lot of problems to be solved. The aim of this study is to pioneer microbial metabolite research and provide a reference for HBP cancer diagnosis, treatment, and prognosis.

Radix Dipsaci (RD) is the dry root of the Dipsacus asper Wall. ex DC., which is commonly used for tonifying the kidney and strengthening bone. The purpose of this study was to analyze the difference between raw and salt-processed RD from the chemical composition comprehensively. The fingerprints of raw and salt-processed RD were established by HPLC-DAD to determine the contents of loganin (LN), asperosaponin VI (AVI), caffeic acid (CaA), dipsanoside A (DA), dipsanoside B (DB), chlorogenic acid (CA), loganic acid (LA), isochlorogenic acid A (IA), isochlorogenic acid B (IB), and isochlorogenic acid C (IC). The results showed that after processing with salt, the components with increased contents were LA, CaA, DA, and AVI, and the components with decreased contents were CA, LN, IB, IA, IC, and DB. Then, the chemometric methods such as principal component analysis (PCA) and fisher discriminant analysis (FDA) were used to evaluate the quality of raw and salt-processed RD. In the classification of raw and salt-processed RD, the order of importance of each chemical component was LA > DB > IA > IC > IB > LN > CA > DA > AVI > CaA. These integrated methods successfully assessed the quality of raw and salt-processed RD, which will provide guidance for the development of RD as a clinical medication.

BACKGROUND:Alzheimer's disease (AD) presently stands as the most prevalent neurodegenerative disease. Existing research underscores the pivotal role of insulin signaling in the progression of AD. Acorus tatarinowii Schott (SCP), a traditional Chinese herbal, is employed for AD treatment in China. The volatile oil of Acorus tatarinowii Schott (SCP-oil) is the active component. However, its impact on AD-associated insulin resistance (AD-IR) remains inadequately investigated. PURPOSE:This study used network pharmacology and experimental to investigate the effects and mechanisms of SCP-oil on cognitive improvement in AD by inhibiting IR. MATERIALS AND METHODS:GC-Q/TOF-MS was employed to analyze the chemical composition of SCP-oil, while network pharmacology predicted the targets associated with SCP-oil in treating AD-IR to identify its regulatory mechanism. IR in the brain was simulated by intracerebroventricular streptozotocin administration (ICV-STZ). The neuroprotective and cognitive improvement effects of SCP-oil were assessed using the Morris water maze and hematoxylin and eosin, as well as Nissl staining. The expression levels of Neun and proteins related to p-tau, tau, amyloid-beta (Aβ), apoptosis, and the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway were measured using immunohistochemistry and Western blotting, respectively. Dexamethasone (DXM)-induced HT22 cells were used for IR modeling. Chemical analysis determined the glucose consumption rate, and periodic acid Schiff staining was employed to detect glycogen deposition. Western Blots were utilized to investigate the expression of characteristic AD proteins, apoptosis-related proteins, and PI3K/AKT pathway-related proteins. The apoptosis rate was detected by flow cytometry. Reverse validation was further performed using LY294002 to evaluate the pharmacodynamic effects of SCP-oil after PI3K/AKT pathway inhibition. RESULTS:A total of 25 chemical constituents were identified in SCP-oil. The network pharmacology findings indicated that SCP-oil holds the potential to ameliorate IR in the brain by activating the PI3K/AKT pathway, thereby improving AD. SCP-oil significantly improved ICV-STZ-induced cognitive dysfunction and pathological damage, reduced neuronal loss, Aβ deposition, and tau protein hyperphosphorylation, inhibited cell apoptosis, and activated the PI3K/AKT signaling pathway. Neuron loss, Aβ deposition, and tau protein hyperphosphorylation and cell apoptosis were further enhanced following treatment with LY294002, while the PI3K/AKT signaling pathway was further inhibited, and the protective effect of SCP-oil was weakened. CONCLUSION:SCP-oil exhibited the potential to ameliorate brain IR, inhibiting cell apoptosis by activating the PI3K/AKT signaling pathway, thereby improving learning and memory ability.