Effectiveness and Safety of Chinese Herbal Injections Combined with SOX Chemotherapy Regimens for Advanced Gastric Cancer: a Bayesian Network Meta-Analysis.

Background: Randomized controlled trials (RCTs) have demonstrated that combining Chinese herbal injections (CHIs) with oxaliplatin plus tegafur (SOX) chemotherapy regimens improves clinical effectiveness and reduces adverse reactions in patients with advanced gastric cancer (AGC). These RCTs highlight the potential applications of CHIs and their impact on AGC patient prognosis. However, there is insufficient comparative evidence on the clinical effectiveness and safety of different CHIs when combined with SOX. Therefore, we performed a network meta-analysis to rank the clinical effectiveness and safety of different CHIs when combined with SOX chemotherapy regimens. This study aimed to provide evidence for selecting appropriate CHIs in the treatment of patients with AGC. Methods: We searched eight databases from their inception until March 2023. Surface Under the Cumulative Ranking Curve (SUCRA) probability values were used to rank the treatment measures, and the Confidence in Network Meta-Analysis (CINeMA) software assessed the grading of evidence. Results: A total of 51 RCTs involving 3,703 AGC patients were identified. Huachansu injections + SOX demonstrated the highest clinical effectiveness (SUCRA: 78.17%), significantly reducing the incidence of leukopenia (93.35%), thrombocytopenia (80.19%), and nausea and vomiting (95.15%). Shenfu injections + SOX improved Karnofsky's Performance Status (75.59%) and showed a significant reduction in peripheral neurotoxicity incidence (88.26%). Aidi injections + SOX were most effective in reducing the incidence of liver function damage (75.16%). According to CINeMA, most confidence rating results were classified as "low". Conclusion: The combination of CHIs and SOX shows promising effects in the treatment of AGC compared to SOX alone. Huachansu and Shenfu injections offer the greatest overall advantage among the CHIs, while Aidi injections are optimal for reducing the incidence of liver damage. However, further rigorous RCTs with larger sample sizes and additional pharmacological studies are necessary to reinforce these findings.

Activation of Pyroptosis Using AIEgen-Based sp2 Carbon-Linked Covalent Organic Frameworks.

Covalent organic frameworks (COFs) have emerged as a promising class of crystalline porous materials for cancer phototherapy, due to their exceptional characteristics, including light absorption, biocompatibility, and photostability. However, the aggregation-caused quenching effect and apoptosis resistance often limit their therapeutic efficacy. Herein, we demonstrated for the first time that linking luminogens with aggregation-induced emission effect (AIEgens) into COF networks via vinyl linkages was an effective strategy to construct nonmetallic pyroptosis inducers for boosting antitumor immunity. Mechanistic investigations revealed that the formation of the vinyl linkage in the AIE COF endowed it with not only high brightness but also strong light absorption ability, long lifetime, and high quantum yield to favor the generation of reactive oxygen species for eliciting pyroptosis. In addition, the synergized system of the AIE COF and αPD-1 not only effectively eradicated primary and distant tumors but also inhibited tumor recurrence and metastasis in a bilateral 4T1 tumor model.

Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension.

Although many studies have addressed the regulatory circuits affecting neuronal activities, local non-synaptic mechanisms that determine neuronal excitability remain unclear. Here, we found that microglia prevented overactivation of pre-sympathetic neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.

Hyperbaric oxygen preconditioning attenuates brain injury after intracerebral hemorrhage by regulating microglia polarization in rats.

AIMS: Hyperbaric oxygen preconditioning (HBOP) attenuates brain edema, microglia activation, and inflammation after intracerebral hemorrhage (ICH). In this present study, we investigated the role of HBOP in ICH-induced microglia polarization and the potential involved signal pathway. METHODS: Male Sprague-Dawley rats were divided into three groups: SHAM, ICH, and ICH + HBOP group. Before surgery, rats in SHAM and HBOP groups received HBO for 5 days. Rats in SHAM group received needle injection, while rats in ICH and ICH + HBOP groups received 100 µL autologous blood injection into the right basal ganglia. Rats were euthanized at 24 hours after ICH, and the brains were removed for immunohistochemistry and Western blotting. Neurological deficits and brain water content were determined. RESULTS: Intracerebral hemorrhage induced brain edema, which was significantly lower in the HBOP group. The levels of MMP9 were also less in the HBOP group. HBO pretreatment resulted in less neuronal death and neurological deficits after ICH. Their immunoactivity and protein levels of M1 markers were downregulated, but the M2 markers were unchanged by HBOP. In addition, ICH-induced pro-inflammatory cytokine (TNF-α and IL-1ß) levels and the phosphorylation of JNK and STAT1 were also lower in the HBOP rats. CONCLUSIONS: HBO pretreatment attenuated ICH-induced brain injuries and MMP9 upregulation, which may through the inhibiting of M1 polarization of microglia and inflammatory signal pathways after ICH.

Cardioprotective Effects of Malvidin Against Isoproterenol-Induced Myocardial Infarction in Rats: A Mechanistic Study.

BACKGROUND Malvidin (alvidin-3-glucoside) is a polyphenol that belongs to the class of natural anthocyanin, which is abundantly found in red wines, colored fruits, and the skin of red grapes. Therefore, the current investigation was intended to evaluate the effect of malvidin against myocardial infarction induced by isoproterenol in the rats. MATERIAL AND METHODS The cardioprotective effects was assessed by determining the effect of malvidin on the activities of endogenous antioxidants - catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) - and on the levels of lipid peroxidation and serum marker enzymes. The serum levels of IL-6 and TNF-α were also determined using an enzyme-linked immunosorbent assay (ELISA) kit. RESULTS The present study demonstrated a significant cardioprotective effect of malvidin by restoring the defensive activities of endogenous antioxidants - catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH) - and by reducing the levels of lipid peroxidation and serum marker enzymes lactate dehydrogenase (LD) and creatine kinase (CK). Malvidin significantly ameliorated the histopathological changes and impaired mitochondria in the cardiac necrosis stimulated with isoproterenol. Additionally, the results also demonstrated that nuclear translocation of Nrf-2 and subsequent HO-1 expression might be associated with nuclear factor kappa B (NF-κB) pathway activation. CONCLUSIONS Our findings suggest that malvidin exerts cardioprotective effects that might be due to possible strong antioxidant and anti-inflammatory activities. Therefore, this study provides the basis for the development of malvidin as a safe and effective treatment of myocardial infarction.

Cloning and expression of two hepcidin genes in the mudskipper (Boleophthalmus pectinirostris) provides insights into their roles in male reproductive immunity.

The mudskipper Boleophthalmus pectinirostris is a burrow-dwelling fish inhabiting intertidal mudflats. During the spawning season, in a spawning chamber located at the center of their burrow, a pair of male and female fish mate and fertilized eggs adheres onto the inner walls and ceiling with filamentous attachments. During 5 days of incubation, the fertilized eggs are kept clean and hatch with a very high hatching rate under the natural conditions filled with microorganisms. This suggests that the male and/or female reproductive tract may synthesize antimicrobial substances to offer protection against microorganisms that may be deleterious to fertility. To study the antimicrobial strategy of this fish in the spawning season, we first cloned the two hepcidin isoforms from B. pectinirostris, and designated them as Hepcidin-1 and Hepcidin-2 based on phylogenetic analyses. Both of these hepcidin isoforms were highly expressed in the liver, but only Hepcidin-1 showed significant change in response to iron overload. Interestingly, these two hepcidin isoforms were expressed in male reproductive tracts, i.e. the testes and seminal vesicles. The monthly expression pattern indicated that Hepcidin-1 transcript levels showed a peak point only in March (before spawning) in the seminal vesicle, while Hepcidin-2 transcript levels were correlated with male reproductive status and reached their highest level in May (the peak spawning period). Under experimental conditions, the expression of these two hepcidin isoforms showed no response to iron overload in the male gonad. However, after lipopolysaccharide injection, the Hepcidin-1 transcript level was significantly up-regulated in the testes and seminal vesicle 6 h post injection, while Hepcidin-2 transcript levels exhibited a clear time-course dependent upregulation pattern and reached the highest levels 24 h post injection. More interestingly, after injection with LHRH-A3, the expression of Hepcidin-2 was significantly up-regulated in both testes and seminal vesicle. Results from in situ hybridization showed that Hepcidin-2 was expressed in the Leydig cells of the testes and in the epithelium of the seminal vesicle. Taken together, the results from our study indicated that these two hepcidin isoforms in the mudskipper may have different functions: Hepcidin-1 may play a dual role in both iron metabolism regulation in the liver and a short antimicrobial response in male reproductive tracts, while Hepcidin-2 is more specialized in reproductive immunity in male reproductive tracts.

Molecular characterization and expression analysis of AMPK α subunit isoform genes from Scophthalmus maximus responding to salinity stress.

AMP-activated protein kinase (AMPK) is a highly conserved and multi-functional protein kinase that plays important roles in both intracellular energy balance and cellular stress response. In the present study, molecular characterization, tissue distribution and gene expression levels of the AMPK α1 and α2 genes from turbot (Scophthalmus maximus) under salinity stress are described. The complete coding regions of the AMPK α1 and α2 genes were isolated from turbot through degenerate primers in combination with RACE using muscle cDNA. The complete coding regions of AMPK α1 (1722 bp) and α2 (1674 bp) encoded 573 and 557 amino acids peptides, respectively. Multiple alignments, structural analysis and phylogenetic tree construction indicated that S. maximus AMPK α1 and α2 shared a high amino acid identity with other species, especially fish. AMPK α1 and α2 genes could be detected in all tested tissues, indicating that they are constitutively expressed. Salinity challenges significantly altered the gene expression levels of AMPK α1 and α2 mRNA in a salinity- and time-dependent manners in S. maximus gill tissues, suggesting that AMPK α1 and α2 played important roles in mediating the salinity stress in S. maximus. The expression levels of AMPK α1 and α2 mRNA were a positive correlation with gill Na+, K+-ATPase activities. These findings will aid our understanding of the molecular mechanism of juvenile turbot in response to environmental salinity changes.

[Effects of two phenolic acids on root zone soil nutrients, soil enzyme activities and pod yield of peanut]. / ä¸¤ç§é šé ¸ç±»ç‰©è´¨å¯¹èŠ±ç”Ÿæ ¹éƒ¨åœŸå£¤å »åˆ†ã€é ¶æ´»æ€§å’Œäº§é‡çš„å½±å“.

In order to investigate the relationship between the accumulation of phenolic acids in peanut continuous cropping soil and the continuous cropping obstacle of peanut, the effects of p-hydroxy benzoic acid and cinnamic acid on peanut root zone soil nutrients, soil enzyme activities and yield of peanut were studied by pot experiment at three stages of peanut, i.e. the pegging stage of peanut (45 days after seedling), the early podding (75 days after seedling) and the end of podding (105 days after seedling) stages. The results showed that the peanut root zone soil nutrients and enzyme activities changed obviously under the two phenolic acids treatment, especially at the pegging stage of peanut. The soil alkali-hydrolyzable nitrogen, available phosphorus, available potassium, and soil enzyme activities (urease, sucrose, neutral phosphatase) were decreased significantly. At the early and end of podding stages of peanut, the effects of the two phenolic acids on peanut root zone soil nutrients and soil enzyme activities were under a weakening trend. The allelopathy of cinnamic acid was stronger than that of p-hydroxy benzoic acid at the same initial content. The pod yield per pot was reduced by 45.9% and 52.8%, while the pod number of per plant was reduced by 46.2% and 48.9% at higher concentration (80 mg·kg-1 dry soil) of p-hydroxy benzoic acid and cinnamic acid treatments, respectively.

Larvicidal activity of lansiumamide B from the seeds of Clausena lansium against Aedes albopictus (Diptera: Culicidae).

The larvicidal activity of crude petroleum ether, toluene, n-butanol, ethyl acetate, acetone, and methanol extracts of the seeds of Clausena lansium was assayed for their toxicities against the early fourth instar larvae of Aedes albopictus. The larval mortality was observed after 24-h exposure. The LC(50) value of petroleum ether extract was 22.99 ppm, showing the best larvicidal activity among all six solvent extracts. A cinnamon amide compound lansiumamide B (N-methyl-N-cis-styrylcinnamamide) was isolated from the petroleum ether extract by column chromatographic method, which exhibited a strong larvicidal activity against the early fourth instar larvae of A. albopictus with LC(50) and LC(90) values of 0.45 and 2.19 ppm, respectively. The structure was elucidated by (1)H NMR, (13)C NMR spectral data. The larvicidal activity against mosquito of lansiumamide B from the seed of C. lansium was evaluated for the first time.

Characterization of RAG1 and IgM (mu chain) marking development of the immune system in red-spotted grouper (Epinephelus akaara).

In vertebrates, lymphoid-specific recombinase protein encoded by recombination-activating genes (RAG1/2) plays a key role in V(D)J recombination of the T-cell receptor and B-cell receptor. In this study, both RAG1 and the immunoglobulin M (IgM) mu chain were cloned to characterize their potential role in the immune defense at developmental stages of red-spotted grouper, Epinephelus akaara. The open reading frame (ORF) of E. akaara RAG1 included 2778 nucleotide residues encoding a putative protein of 925 amino acids, while the ORF of the IgM mu chain had 1734 nucleotide residues encoding 578 amino acids including variable (VH) and constant (CH1-CH2-CH3-CH4) regions. E. akaara RAG1 was composed of a zinc-binding dimerization domain (ZDD) with a RING finger and zinc finger A (ZFA) in the non-core region and a nonamer-binding region (NBR), with a zinc finger B (ZFB), the central and C-terminal domains in the core region. Tridimensional models of the ZDD and NBR of E. akaara RAG1 were constructed for the first time in fishes, while a 3D model of the E. akaara IgM mu chain was also clarified. The RAG1 mRNA was only detected in the thymus and kidney of 4-month and 1.5-year old groupers using qPCR, and the RAG1 protein was confirmed using western blotting and immunohistochemistry. The IgM mu mRNA was examined in most tissues except the gonad. RAG1 and IgM mu gene expression were observed at 15 dph (days post-hatching) and 23 dph respectively, and increased to a higher level at 37 dph. In addition, this was the first time that the morphology of the E. akaara thymus was characterized. The oval-shaped thymus of 4-month old fish was clearly seen and there were amounts of T lymphocytes present. The results suggested that the immune action of E. akaara was likely to start to develop around 15 dph to 29 dph. The transcript level of the RAG1 gene and the number of lymphocytes in the thymus between 4-month and 1.5-year old groupers indicated that age-related thymic atrophy also occurs in fishes. The similar functional structures of RAG1 and IgM protein between fish and mammals indicated that teleost species share a similar mechanism of V(D)J recombination with higher vertebrates.

[Determination of lignin content in tiny Panax ginseng by UV spectrophotometry].

OBJECTIVE: To establish the UV spectrophotometry for determining lignin content in tiny Panax ginseng powder. METHODS: Classical Klason method and UV spectrophotometry were used. RESULTS: The lignin contents measured by UV spectrophotometry were higher, more repeatable and accurate as comparison with the Klason method. The specific absorptance peak of ginseng lignin appeared at 260 nm. The acetyl bromide treatment of the UV spectrophotometry was processed for ginseng powder at 70 degrees C for 30 minutes. It is also concluded that the lignin contents were obvious different among various ginsengs. CONCLUSION: UV spectrophotometry is simple, accurate and just need a little materials. It is especially suitable to determine the lignin content for ginseng and other precious Chinese traditional medicines.