To explore the potential active components and underlying mechanisms of Buzhong Yiqi Decoction (BZYQD) in ameliorating chemotherapy-induced sarcopenia (CIS) using integrated strategies of network pharmacology and in vivo validation.

The active components of BZYQD and their targets were identified using the TCMSP platform. CIS-related targets were obtained from the GeneCards and OMIM databases. We constructed a protein-protein interaction network by taking the intersection targets of drugs and diseases and identifying the core targets. We carried out gene ontology (GO) functional annotation and kyoto encyclopedia of genes and genomes pathway (KEGG) enrichment. Molecular docking and visualization were performed using AutodockTools 1.5.7 and PyMOL 2.7.1. The therapeutic effects of BZYQD on CIS were validated in animal experiments.

The core targets at the drugs/diseases intersection included Akt1, TP53, tumor necrosis factor (TNF), interleukin (IL)-1β, and IL-6. Molecular docking analysis indicated that the core targets and main active components had favorable binding affinities. In the experiment on SD rats, body mass, grip strength, exhaustive swimming time, and myofiber cross-sectional area were significantly decreased in the model (M group) compared with the control group (C group). Serum levels of TNF-α, IL-1β, and IL-6 detected by enzyme-linked immunosorbent assay were significantly elevated. The phospho (p)-nuclear factor (NF)-κB p65/NF-κB p65 ratio was significantly increased, while the p-Akt/Akt and p-phosphoinositide 3-kinase (PI3K)/PI3K ratios were significantly decreased, as shown by Western Blot. Administration of BZYQD ameliorated these alterations in a dose-dependent manner, with the most pronounced effects in the HBYD group.

BZYQD may improve CIS by regulating the PI3K/Akt/NF-κB signaling pathway.

To determine the absorption rate and anti-osteoporosis efficacy of calcium zinc vitamin D vitamin K oral solution (YQJ) and its components in Caco-2 cells and zebrafish, and explore its potential mechanism based on transcriptome sequencing.

We compared the calcium-ion absorption rates of YQJ and its components in Caco-2 cells, to simulate gastrointestinal absorption. An osteoporosis model was induced using dexamethasone. Bone density was detected by Alizarin Red staining and dual validation of drug efficacy was analyzed using transgenic (ola. sp7: nlsGFP) osteoblast fluorescence. Zebrafish were divided into YQJ 250 μg/mL, MC, and NC groups (3 biological replicates each). Transcriptome sequencing was carried out and differentially expressed genes at the intersection of the three groups were screened using | log₂ fold-change| ≥ 2 and Q value ≤ 0.001. Differential genes underwent functional annotation and enrichment analyses to screen out the expression pathway of YQJ anti-osteoporosis genes, followed by quantitative polymerase chain reaction validation.

The absolute calcium-absorption rate in YQJ-treated Caco-2 cells was 42.6%, which was 1.70 fold higher than that of the calcium citrate-alone group, 1.59, 1.58, and 1.56 fold higher than the calcium citrate + vitamin (V) D₃, calcium citrate + VK₂, and calcium citrate + (casein phosphopeptides) CPP groups, respectively, and 1.33 fold higher than the calcium citrate + zinc gluconate + D₃ group, indicating a significant synergistic effect of YQJ on promoting calcium absorption. YQJ significantly restored zebrafish skull density and increased osteogenic fluorescence intensity, and 125 μg/mL YQJ increased the anti-osteoporosis effect by 24% ~ 25% compared with calcium citrate alone. Sequencing identified 335 and 231 differentially expressed genes in MC group/NC group and YQJ group/MC group, respectively, with 58 overlapping genes at the intersection of the three groups. Functional enrichment of overlapping genes revealed that YQJ's anti-osteoporosis effect involved four pathways and 11 key genes. Using qPCR verification, YQJ significantly restored the mRNA expression levels of c3a. 1, cp, coro1a, cldni, and bmpr1aa.

The in vitro calcium-absorption rate and anti-osteoporosis efficacy of YQJ both demonstrated synergistic effects, with its anti-osteoporosis effect specifically increasing skull density and osteoblast signaling intensity. Transcriptome sequencing revealed that YQJ primarily functions by modulating the complement and coagulation cascade, ferroptosis, phagosome, oxidative stress response signaling pathways, and other functional proteins, involving the regulation of key genes such as c3a. 1, c3a. 2, c3a. 6, c9, c5, cfb, coro1a, cp, mpx, cldni, and bmpr1aa.

To investigate the differential therapeutic effects of XuanFei HuaZhuo pill (XFHZP) on rat pneumonia models with damp-heat pneumonia (DH) syndrome, and to elucidate the underlying mechanisms using proteomics, to provide experimental evidence for the use of traditional Chinese medicine (TCM) in the treatment of pneumonia.

A DH group model was established. Therapeutic effects were evaluated via clinical signs and scores (general information, tongue, ear, claw nail, urine, feces), lung index, histopathology (hematoxylin-eosin), enzyme-linked immunosorbent assay for pulmonary interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels, hematology (white blood cell count (WBC), granulocytes (Gran), monocytes (Mon), mean platelet volume (MPV)), and pulmonary function (respiratory frequency (F), minute ventilation (MV)). Astral data-independent acquisition quantitative proteomics was performed on the right inferior lung lobes from control (CON) group, DH group, and XFHZP + DH group to identify differentially expressed proteins (DEPs) between CON vs. DH and DH vs. XFHZP + DH groups. Key DEPs were verified by immunohistochemistry and Western Blot, including their downstream targets (phospho-MLC2, phospho-eIF4E).

Compared with CON group, DH group exhibited hyperactive behavior, red tongues, ear-vessel dilation, yellow urine, and sticky feces, and displayed elevated lung indices, alveolar wall thickening, inflammatory infiltration, and capillary congestion, plus increased IL-6 and TNF-α (P < 0.05), WBC, Gran, Mon, MPV, F (P < 0.05), and reduced MV (P < 0.05). XFHZP treatment significanly ameliorated lung pathology, reduiced IL-6、TNF-α (P < 0.05), and nomalized WBC、Gran、Mon、MPV、F (P < 0.05), MV (P < 0.05) in DH rats (XFHZP + DH). Proteomics identified 1348 DEPs in the CON vs. DH and 448 in the DH vs. XFHZP + DH group, including AAK1、CACNα2δ1、eIF4E、HSD11β1、ROCK1、TDP1. KEGG analysis highlighted cGMP-dependent protein kinase G and insulin-signaling pathways as potential mechanisms for XFHZP in DH pneumonia. ROCK1/MKNK1 was upregulated in DH lungs, accompanied by increased MLC2/eIF4E phosphorylation, which were suppressed by XFHZP.

XFHZP exerts significant therapeutic effects on DH syndrome pneumonia, likely by downregulating ROCK1/MKNK1 expression, inhibiting MLC2/eIF4E phosphorylation, relaxing airway smooth muscle, and attenuating inflammation. This study provides molecular-level evidence for XFHZP's efficacy and offers novel insights into TCM-based pneumonia treatment.

To construct and evaluate a mouse model of pressure overload-induced heart failure with dampness syndrome.

C57BL/6 mice were divided randomly into sham, thoracotomy and aortic restriction (TAC), and TAC-dampness (TAC-D) groups (n = 7 mice per group). Mice in the sham group underwent thoracotomy without aortic constriction, while mice in the TAC group underwent aortic arch constriction to induce pressure overload-induced heart failure. All mice were housed in a normal environment. In addition to TAC surgery, TAC-D mice were placed in a controlled temperature and humidity chamber for 8 h/d to induce dampness syndrome, with the remaining time spent in a normal environment. This protocol was maintained for 8 weeks. The macroscopic manifestations were assessed using the "Evaluation Scale for Dampness Syndrome Animal Models in Traditional Chinese Medicine". Modern medical techniques were employed to measure cardiac function, myocardial histopathology, immune homeostasis, serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), and lipid levels. Fecal 16S rDNA sequencing and serum non-targeted metabolomics were conducted to develop novel evaluation indicators for the heart failure with dampness syndrome mouse model.

Mice in the TAC-D group exhibited fatigue, lethargy, reduced responsiveness to external stimuli, and anal soiling. Mice in both heart failure groups demonstrated marked cardiac dysfunction, myocardial injury, immune homeostasis imbalance, elevated serum NT-proBNP levels, and reduced lipid levels, especially in the TAC-D group. Fecal 16S rDNA sequencing and serum non-targeted metabolomics revealed significant alterations in the gut microbiota and metabolites following dampness syndrome induction. Linear discriminant analysis effect size analysis (> 2) showed that the bacterial genera Enterorhabdus, Eubacterium, Corynebacterium, Christensenellaceae and Erysipelatoclostridium were significantly enriched in the TAC-D group. Metabolomics kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis indicated that differential metabolites in the TAC-D group were primarily enriched in glycerophospholipid metabolism, arachidonic acid metabolism, and bile secretion pathways. Pearson's correlation analysis revealed significant negative correlations between the bacterial genera Eubacterium and Erysipelatoclostridium and metabolites involved in arachidonic acid metabolism, including 16R-hydroxy-5,8,11,14-eicosatetraenoic acid (HETE), 6-keto PGE1, PE-NMe2(16 ∶ 1(9Z)/20 ∶ 3(8Z, 11Z, 14Z)), Prostaglandin F2a, TXB2, Oxoglutaric acid, and 12 (R)-HETE.

The combination of aortic arch constriction and a controlled temperature and humidity environment successfully established a mouse model of pressure overload-induced heart failure with dampness syndrome. The "Evaluation Scale for Dampness Syndrome Animal Models in Traditional Chinese Medicine", cardiac function, serum NT-proBNP, myocardial histopathology, and immune homeostasis can serve as conventional evaluation indicators for this model. Additionally, the incorporation of disturbances in the gut bacterial genera Eubacterium and Erysipelatoclostridium and arachidonic acid metabolism further develops an innovative evaluation system for the heart failure with dampness syndrome mouse model.

To establish and characterize two chronic stress-related dry-eye models using chronic unpredictable mild restraint (CUMR) and chronic unpredictable rhythm disturbance (CURD), respectively, and to compare their phenotypic presentations, metabolomic profiles, and correlations with traditional Chinese medicine syndrome patterns.

Healthy male specific-pathogen-free rats were divided into control, CUMR, and CURD groups. Rats in the CUMR group underwent single-cage housing combined with behavioral restraint daily, while CURD rats received random daily rhythm interventions. After 6 weeks of modeling, dry-eye rats associated with Yu syndrome were assessed for general conditions, behavioral performance, and dry-eye parameters. Histopathological alterations in the conjunctiva, cornea, and lacrimal gland were examined by hematoxylin-eosin staining. Serum concentrations of 5-hydroxytryptamine (5-HT) and cortisol, and cornea levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), were quantified by enzyme-linked immunosorbent assay. Serum metabolomic profiling was conducted using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

(1) There were significant differences in appearance and behavior between the CUMR and CURD groups. (2) Compared with the control group, cornea fluorescein staining(CFS) was significantly increased in the CUMR and CURD groups, while tear flow and tear-film breakup time (BUT) were significantly decreased, especially in the CUMR group. (3) There was no obvious inflammatory cell infiltration in the cornea in the CUMR or CURD group. Compared with the control group, there were significantly fewer conjunctival goblet cells in the CUMR and CURD groups, and the area of lacrimal gland vacuolation was significantly increased. (4) Serum 5-HT was significantly decreased and cortisol was significantly increased in the CUMR group compared with the CURD group, but there were no significant differences in cornea tissue TNF-α and IL-1β levels. (5) Serum metabolomic analysis revealed 235 differential metabolites in the CUMR and CURD groups, demonstrating a significant separation trend.

Distinct stress-modeling paradigms differentially impact host metabolism, culminating in divergent TCM syndrome manifestations and dry-eye phenotypes. The CUMR model exemplifies a dry-eye phenotype consistent with "Liver Depression and Spleen Deficiency," potentially mediated by perturbations in tryptophan metabolism, while the CURD model aligns with "Stagnation Heat in the Liver Channel," likely arising from disruptions in the tricarboxylic acid cycle.

To investigate renal injury, functional impairment, histopathological characteristics, and molecular features accompanying HCC development in the context of non-alcoholic steatohepatitis, utilizing a novel MASH-HCC murine model (HRAS-HCC). This research seeks to elucidate the underlying mechanisms of MASH-HCC-induced renal injury, thereby providing an essential model tool for clinical investigations into disease pathogenesis and the exploration of diagnostic and therapeutic strategies.

HRAS-HCC transgenic mice generated in-house were employed, with littermate negative controls and wild-type C57BL/6 mice as comparators. At 5 weeks of age, tamoxifen was administered to induce hepatocyte-specific HRAS expression, thereby initiating and propagating MASH-HCC. Body mass, general condition, and behavioral parameters were monitored serially during disease progression (weeks 1 ~ 4). Blood was collected at predetermined time points for biochemical analyses. Structural and fibrotic changes in renal tissue were evaluated by hematoxylin-eosin(HE) and Masson staining.

Compared with the HRAS^NON-TAM group, Within 4 weeks, HRAS-HCC mice transitioned from MASH through hepatic fibrosis to established HCC, manifesting jaundice, tachypnea, kyphosis, hematochezia, hepatosplenomegaly, and other clinical signs. At week 4, serum alkaline phosphatase(ALP) was significantly decreased (P < 0.05), whereas blood urea nitrogen(UREA), uric acid(UC), and creatinine(CREA) were markedly elevated (P < 0.05). HE staining revealed temporally heterogeneous renal lesions, including tubular basophilia, hyaline glomerulopathy, and tubular epithelial cytoplasmic hyaline droplet formation. Masson staining demonstrated renal fibrosis whose onset (weeks 2 ~ 3) and severity paralleled those of hepatic fibrosis/cirrhosis(weeks 2 ~ 3). Further analysis of kidney injury-related molecular expression revealed at week 3 showed up-regulation of keratin-18, SMAD3, fibronectin, and transforming growth factor-β mRNAs (P < 0.05). Protein-protein interaction analyses further indicated direct interactions among human HRAS, fibronectin (FN1), and SMAD3.

These data establish a positive correlation between MASH HCC-induced renal injury and the degree of hepatic fibrosis, clarify the attendant histopathological and molecular signatures, and implicate the HRAS-SMAD3-FN1 axis as a putative mechanistic pathway. The HRAS-HCC mouse model uniquely recapitulates key clinicopathological features of human MASH-HCC complicated by CKD, thereby providing a robust pre-clinical platform for mechanistic dissection and therapeutic development.

To investigate the effects and underlying mechanisms of Lonicera japonica in delaying renal aging.

A mouse model of renal aging was established via intraperitoneal injection of D-galactose (D-gal), with concurrent administration of Lonicera japonica decoction by oral gavage. Following behavioral assessments, kidney tissues were collected from each group for enzyme-linked immunosorbent assay (ELISA) and senescence-associated β-galactosidase (SA-β-gal) staining to evaluate model induction and the protective effects of Lonicera japonica. Integrated microRNA (miRNA) transcriptomic and proteomic sequencing analyses were conducted to identify significantly differentially expressed miRNA (DEMs) and protein (DEPs). Functional annotation and pathway enrichment of these DEMs and DEPs were performed using gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) databases.

Behavioral tests, including the Morris water maze and forced swimming test, revealed significant impairments in learning, memory, and exercise endurance in model mice compared with controls (P < 0.05). Lonicera japonica markedly ameliorated these aging-related deficits (P <0.05). Renal interleukin (IL)-6 levels and the percentage of SA-β-gal-positive area were significantly elevated in the model group relative to the control group (P < 0.001), and both were significantly reduced following Lonicera japonica intervention (P < 0.01). Integrated omics analysis identified 11 significant DEMs and eight significant DEPs. Intersection analysis of target genes revealed miR-146b-3p/Tmprss13 as a key regulatory pair, while miR-150-3p/Brpf1 and miR-1934-5p/Cln8 were identified as miRNA-protein pairs concurrently downregulated by Lonicera japonica. GO and KEGG enrichment analyses indicated that Lonicera japonica may delay renal aging by activating Lonicera japonica-regulated Ecsit (LjREcsit), a differentially expressed gene involved in the mitogen-activated protein kinase (MAPK) signaling pathway.

Lonicera japonica attenuates D-gal-induced renal aging in mice, possibly via mechanisms involving inhibition of miR-146b-3p leading to activation of Tmprss13, or coordinated downregulation of miR-150-3p/Brpf1 and miR-1934-5p/Cln8. Modulation of the MAPK signaling pathway via LjREcsit also represents a critical mechanism through which Lonicera japonica exerts its renoprotective and anti-aging effects.

To compare the composition and diversity of lung and gut microbiota between Chinese and golden hamsters using 16S rDNA sequencing, to provide a new perspective for understanding their applications in human disease research.

SPF-grade Chinese hamsters and golden hamsters (6 males and 6 females per group) aged 6 ~ 8 weeks were selected. Bronchoalveolar lavage fluid, small intestinal contents, and large intestinal contents were collected under sterile conditions. Species annotation and α-diversity and β-diversity analyses were performed using 16S rDNA sequencing. Linear discriminant analysis effect size (LEfSe) analysis was employed to identify potential biomarkers.

The α-diversity of the lung and small intestinal microbiota was significantly higher in golden hamsters (especially males) than in Chinese hamsters (P < 0.05), while the diversity of the large intestinal microbiota was significantly higher in Chinese hamsters (P < 0.05). Regarding β-diversity, the composition of the lung, small intestinal, and large intestinal microbiota differed significantly between the two types of hamsters (P < 0.01). LEfSe analysis revealed differential occurrence of the phylum Firmicutes in the lung microbiota in golden hamsters, and differential occurrence of the phyla Bacteroidota (females) and Proteobacteria (males) in Chinese hamsters. Regarding the small intestinal and large intestinal microbiota, Firmicutes and Bacteroidota were differential phyla in Chinese and golden hamsters, respectively.

The composition and diversity of the lung and gut microbiota differed significantly between Chinese and golden hamsters, which may be related to their distinct applications in human disease research. This study provides a new perspective for understanding the applications of these two types of hamsters in human disease research and lays a theoretical foundation for future efforts to improve their health status and their value as experimental models by modulating their microbiota.