Search Results (51)

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

Cytokinins, plant hormones derived from adenine, are best known for regulating growth and stress responses in plants. Recent findings suggest they may also influence microbial viability, yet their direct antimicrobial potential remains underexplored. This study evaluates the antimicrobial activities of four natural cytokinins (iPA, B, K, and p-T) and their N⁹-ribosides (iPAR, BR, KR, and p-TR) against selected human pathogens. Using the broth microdilution method, we assessed their effects on Gram-positive and Gram-negative bacteria, as well as fungal strains. While Gram-negative species showed no susceptibility, all tested compounds exhibited bacteriostatic activity against Bacillus subtilis and Enterococcus faecalis. Most notably, kinetin (K) and kinetin riboside (KR) displayed strong antifungal activity against Candida albicans, with MIC values comparable to the reference drug nystatin. Molecular docking studies supported these findings by showing that K and KR form favorable interactions with two validated antifungal targets in Candida albicans: secreted aspartic proteinase 3 (SAP3) and dihydrofolate reductase (DHFR). This is, to our knowledge, the first report linking natural cytokinins to direct antifungal action against C. albicans supported by in silico evidence. These findings highlight the potential of K and KR as promising leads for the development of cytokinin-based antifungal agents. Full article

Research on functional recovery after ischemic stroke has primarily focused on non-invasive brain stimulation and motor rehabilitation therapies, while direct pharmacological interventions are relatively underexplored. This study utilized a bidirectional Mendelian randomization approach to investigate the causal relationship between 191 resting-state functional magnetic resonance imaging (rs-fMRI) features and post-ischemic stroke functional recovery (PISFR). Significant rs-fMRI phenotypes were identified, and Mendelian randomization was employed to determine their associated proteins. Bidirectional Mendelian randomization identified four rs-fMRI phenotypes potentially associated with functional recovery after ischemic stroke. Subsequent MR analysis, using pheno12 as the outcome and plasma protein as the exposure, highlighted Fas-Associated protein with Death Domain (FADD) as a significant protein. Further exploration within the protein–protein interaction (PPI) network identified FADD, Cysteinyl Aspartate Specific Proteinase 8 (CASP8), and Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) as potential drug targets. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that these proteins are involved in the extrinsic apoptotic pathway, providing new insights for pharmacological strategies in post-ischemic stroke recovery. This study offers genetic evidence linking rs-fMRI to functional recovery post-ischemic stroke and identifies potential drug targets that may facilitate therapeutic interventions to enhance recovery after ischemic stroke. Full article

Background: Agarwood has been widely used for the treatment of gastrointestinal diseases. Our research group has suggested that agarwood alcohol extracts (AAEs) provide good gastric mucosal protection. However, the exact mechanisms underlying this effect remain unclear. Objectives: This study aimed to investigate the ameliorative effect of agarwood chromone on gastric ulcers and its mechanism. Methods: Network pharmacology was used to predict the disease spectrum and key therapeutic targets of 2-(2-phenylethyl)chromone (CHR1) and 2-(2-(4-methoxyphenyI)ethyl)chromone (CHR2). Mice were orally administered CHR1 (20 and 40 mg/kg) and CHR2 (20 and 40 mg/kg) and the positive drug omeprazole as an enteric-coated capsule (OEC, 40 mg/kg) orally. After 7 days of pretreatment with the CHRs, gastric ulcers were induced using absolute ethanol (0.15 mL/10 g). The ulcer index, gastric histopathology, biochemical parameters, and inflammatory and apoptotic proteins were evaluated. Finally, binding of the core compounds to the key targets was verified via molecular docking and visualized. Results: The pharmacological results show that the CHRs reduced the gastric occurrence and ulcer inhibition rates by up to more than 70% in a dose-dependent manner. The CHRs decreased the levels of interleukin 6 (IL-6), interleukin 12 (IL-12), interleukin 18 (IL-18), and tumor necrosis factor α (TNF-α), and improved the severity of the pathological lesions in the gastric tissue. The expression of ATP-binding box transporter B1 (ABCB1), arachidonic acid-5-lipoxygenase (ALOX5), nuclear factor kappa B (NF-κB), cysteinyl aspartate specific proteinase 3 3 (Caspase3), and cysteinyl aspartate specific proteinase 9 (Caspase9) was inhibited, but the expression of B-cell lymphoma-2 (Bcl-2) was enhanced. The CHRs bound stably to the key targets via hydrogen bonding, van der Waals forces, etc. These results demonstrate that agarwood chromone compounds exert alleviative effects against the occurrence and development of gastric ulcers by inhibiting the NF-κB and caspase pathways. The CHRs have a therapeutic effect on gastric ulcers through anti-inflammation and anti-apoptosis mechanisms. Conclusions: This study suggests that agarwood may have a potential role in drug development and the prevention and treatment of gastrointestinal inflammation, and tumors. Full article

Metabolic dysfunction-associated fatty liver disease (MAFLD) affects approximately one-quarter of the world’s adult population, and no effective therapeutic drugs are available. Poria cocos is a fungus used as a herb and food nutrient for centuries as well as for MAFLD treatment. Exosome-like nanovesicles have many pharmacological activities; however, studies on the effects of Poria cocos-derived exosome-like nanovesicles (PCELNs) on MAFLD are lacking. Therefore, our study aimed at identifying the effects and mechanism of action of PCELNs on MAFLD. PCELNs were isolated by ultracentrifugation and their morphology was characterized, such as particle size, zeta potential, protein distributions, as well as lipid and miRNA compositions. Then, the absorption and distribution of PCELNs were observed in vivo and in vitro. Finally, L02 cell steatosis model induced by fat emulsion and MAFLD mouse model induced by high-fat diet (HFD) were used to evaluate the effect and mechanism of PCELNs on MAFLD. PCELNs were membrane structured vesicles, with a particle size of 161.4 ± 1.7 nm, a zeta potential of −3.20 ± 0.37 mV, and contained a range of proteins, lipids, and miRNAs. PCELNs were absorbed by L02 cells and targeted the liver and spleen after intraperitoneal injection. PCELNs inhibited body weight gain and improved the index of heart, liver, spleen, and various fats, as well as decreased lipid accumulation and lipid level. They also protected mitochondrial ultrastructure and regulated oxidative stress and energy metabolism disorder. Furthermore, PCELNs increased PTEN induced kinase 1 (PINK1), E3 ubiquitin ligase (Parkin) and microtubule associated protein light chain-3 (LC3) protein expression in the liver, reduced oxidized mitochondrial DNA (Ox-mtDNA) content in mitochondria and cytoplasm of the liver, reduced nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3), pro-cysteinyl aspartate specific proteinase-1 (caspase-1), cleared-caspase-1, and mature-interleukin-1β (IL-1β) protein expression in the liver, and reduced the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and interleukin-18 (IL-18) in serum and liver. In conclusion, we demonstrated that PCELNs may alleviate HFD-induced MAFLD by promoting mitochondrial autophagy and inhibiting NLRP3 inflammasome activation. Full article

In this work, we describe the synthesis of three new meso-arylporphyrins, named meso-tetrakis [4-(nicotinoyloxy)phenyl] porphyrin (H₂TNPP), meso-tetrakis [4-(picolinoyloxy)phenyl] porphyrin (H₂TPPP), and meso-tetrakis [4-(isonicotinoyloxy) phenyl] porphyrin (H₂TIPP). These new synthesized meso-arylporphyrins are characterized using spectroscopic analysis: Fourier Transform Infrared Spectroscopy (FTIR) and One-dimensional Nuclear Magnetic Resonance (1D NMR), and mass spectrometry (MS). The photophysical studies (UV–visible absorption, singlet oxygen (¹O₂) luminescence, and fluorescence emissions) demonstrate their potential uses as photosensitizers (PSs) in photodynamic therapy (PDT) applications. An in vitro investigation of the anti-fungal activity of H₂TNPP, H₂TPPP, and H₂TIPP against Candida (C.) species (C. albicans, C. glabrata, and C. tropicalis) reveals that their minimum inhibitory concentration (MIC) values ranged from 1.25 to 5 mg/mL. In addition, their in vitro anti-fungal susceptibilities against three dermatophyte clinical isolates (Trichophyton rubrum, Microsporum canis, and Trichophyton mentagrophytes) are also evaluated and they demonstrate good anti-fungal activities. A molecular docking study of these meso-arylporphyrins as anti-fungal agents against C. tropicalis extracellular aspartic proteinases, Protein data Bank in Europe (PDBe code: 1J71) and Trichophyton rubrum Sialidases (PDBe code: 7P1D) underlines the possible interactions of H₂TNPP, H₂TPPP, and H₂TIPP with the key amino acid residues of these fungal target proteins. Full article

This work aimed to evaluate the effects of dried apple pomace (DAP) on the fermentation characteristics and proteolysis of alfalfa silages. The alfalfa was ensiled with (1) no additives (control), (2) 5% DAP, (3) 10% DAP and (4) 15% DAP based on fresh weight (FW) for 1, 3, 7, 14, 30 and 60 days, respectively. With the increasing proportion of DAP, lactic acid bacteria (LAB) count, lactic acid (LA) and dry matter (DM) content linearly (p < 0.05) increased, while the pH, the content of acetic acid (AA), propionic acid (PA), butyric acid (BA) and ammonia nitrogen (NH₃-N) linearly (p < 0.05) decreased during ensiling. The 10% and 15% DAP silages had significantly (p < 0.05) lower aerobic bacteria (AB), yeast and enterobacteria counts than the control during ensiling. The contents of nonprotein nitrogen (NPN), peptide nitrogen (peptide-N) and free amino acid nitrogen (FAA-N) and activities of carboxypeptidase, aminopeptidase and acid proteinase linearly (p < 0.05) decreased as DAP proportion increased during ensiling. On day 60, the addition of DAP significantly (p < 0.05) decreased the contents of tryptamine, phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, spermine and total biogenic amines compared with the control. As the DAP ratio increased, the contents of threonine, valine, isoleucine, leucine, phenylalanine, lysine, histidine, arginine, aspartic acid, serine, glutamic, total amino acids, crude protein (CP) and water-soluble carbohydrates (WSCs) linearly (p < 0.05) increased, while the contents of glycine, alanine, cysteine, and proline linearly (p < 0.05) decreased on day 60. Overall, the addition of 15% DAP was optimal as indicated by better fermentation quality and less proteolysis than other treatments. Full article

Background and Objective: In Saudi Arabia, numerous plant species with promising medicinal properties are cultivated, widely traded, and commonly utilized in traditional medicine, including fenugreek (Trigonella foenum-graecum). This study aimed to comprehensively assess the phytochemical composition and antimicrobial potential of the Saudi cultivar of fenugreek using an integrative approach combining in vitro and in silico methodologies. Methods: A comprehensive investigation was conducted on the ethanol extract of fenugreek seeds, assessing its antibacterial, antifungal, properties. Computational modeling was employed to predict pharmacokinetic behavior and potential toxicity of the identified bioactive compounds. Results: Qalitative phytochemical analysis showed presence of alkaloids, tannins, saponins, glycosides, flavonoids, and steroids, while terpenoids were notably absent. GC-MS analysis of Trigonella foenum-graecum (fenugreek) seeds identified 25 bioactive compounds, with Ethyl methane sulfonate (12.41%) being the predominant component. Other key compounds included n-Hexadecanoic acid, 4-Butyl-2(4-nitrophenyl)-1,3-thiazole, and α-Tocopherol. In silico modeling of fenugreek phytochemicals supported their antibacterial, antioxidant, and neuroprotective potential, with compounds 21 and 24 showing strong binding to key targets like Tyrosyl-tRNA Synthetase (TyrRS) of Staphylococcus aureus (S. aureus), Aspartic proteinase from Candida albicans (C. albicans) and human peroxiredoxin 5. Pharmacokinetic analysis indicated good oral bioavailability, minimal CYP inhibition, and blood-brain barrier penetration, suggesting potential for treating neurodegenerative diseases. These bioactive compounds, including diosgenin and trigonelline, support fenugreek’s therapeutic promise and warrant further in vitro, in vivo, and clinical studies. Conclusion: The Saudi fenugreek cultivar is rich in bioactive compounds with good antibacterial potential. These findings establish a robust foundation for continued pharmacological research on the Saudi cultivar of T. foenum-graecum, highlighting its potential as a rich source of bioactive compounds with significant medicinal value. Full article

Background: Barrett’s esophagus (BE), with metaplastic columnar epithelium in the lower esophagus, predisposes patients to esophageal adenocarcinoma (EAC). Despite extensive research, mechanisms underlying BE progression to EAC remain unclear, and no validated biomarkers are available for clinical use. Progastricsin/Pepsinogen-C (PGC), an aspartic proteinase linked to maintaining normal epithelial morphology, is often absent in advanced gastrointestinal malignancies. This study comprehensively investigates PGC expression across cancers, particularly in esophageal cancer (ESCA), to clarify its role in BE progression to EAC. Methods: We utilized multiple bioinformatic platforms (TIMER, UALCAN, cBioPortal, GEPIA, STRING, Metascape, and GEO database) to assess PGC expression, genomic alterations, and correlations with clinicopathological features, survival, and immune infiltration. Additionally, using the GEO dataset, we compared non-dysplastic Barrett’s esophagus (NDBE) patients with those who progressed to malignancy, identifying differentially expressed genes (DEGs), their interactions, and potential roles in progression. Results: PGC was notably upregulated in various cancers, especially in adjacent normal tissues of ESCA. Genomic amplifications of PGC were linked to improved survival in EAC patients, particularly those with high PGC expression, suggesting a protective role. Moreover, PGC expression positively correlated with favorable immune infiltration, notably B cells and CD8+ T cells. Enrichment analysis of downregulated DEGs revealed significant involvement in key biological processes, specifically in extracellular matrix organization. Among the downregulated DEGs, we identified PGC among the top 10 hub genes, underscoring its role in tissue homeostasis. Conclusions: These findings suggest that PGC could serve as a promising biomarker for predicting the high-risk transformation from BE to EAC, offering new insights into EAC progression and future therapeutic targets. Full article

Background/Objective: Indwelling intrauterine contraceptive devices (IUDs) have surfaces that facilitate the attachment of Candida spp., creating a suitable environment for biofilm formation. Due to this, vulvovaginal candidiasis (VVC) is frequently linked to IUD usage, necessitating the prompt removal of these devices for effective treatment. In this study, we evaluated the susceptibility of antimicrobial peptides in vitro against biofilm forming, Amphotericin B (MIC50 > 2 mg L⁻¹) resistant Candida krusei and Candida tropicalis isolated from IUD users who had signs of vaginal candidiasis (hemorrhage, pelvic pain, inflammation, itching, and vaginal discharge). Three antimicrobial peptides, namely, epinecidin-1 (epi-1) and its two variants, namely, variant-1 (Var-1) and variant-2 (Var-2), which were reported to have enhanced antibacterial activity were tested against IUD isolates (C. krusei and C. tropicalis) with pathogenic form of Candida albicans as control. Variants of epi-1, namely, Var-1 and Var-2 were created by substituting lysine in the place of histidine and alanine. Methods: The antimicrobial activity was measured using the microbroth dilution method to determine the minimum inhibitory concentration (MIC) of peptides against C. albicans, C. krusei and C. tropicalis. The MIC of each peptide was used for biofilm assay by Crystal violet staining, Scanning Electron Microscopy, and Reactive Oxygen Species (ROS) assay. To find the possible mechanism of anti-biofilm activity by the peptides, their ability to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2 were determined through PatchDock. Results: The MIC values of peptides: epi-1, var-1 and var-2 against C. albicans are 128 μg mL⁻¹, 64 μg mL⁻¹ and 32 μg mL⁻¹, C. tropicalis are 256 μg mL⁻¹, 64 μg mL^−1, and 32 μg mL⁻¹ and C. krusei are 128 µg mL⁻¹, 128 µg mL⁻¹ and 64 µg mL⁻¹, respectively. Both the variants outperformed epi-1. Specifically for tested Candida spp., var-1 showed two- to four-fold enhancements and var-2 showed two- to eight-fold enhancements compared to epi-1. Electron microscopy confirmed that the mechanism of action involves pore formation thus inducing reactive oxygen species in Candida spp. cell membrane. Computational analysis showed that the peptides have a high tendency to interact with Candida spp. cell membrane proteins such as Exo-β-(1,3)-Glucanase, Secreted Aspartic Proteinase (Sap) 1, and N-terminal Domain Adhesin: Als 9-2, thereby preventing biofilm formation. Conclusions: The in vitro evidence supports the potential use of epi-1 and its variants to be used as an anti-biofilm agent to coat IUDs in the future for therapeutic purposes. Full article

Tick eggs contain a series of proteins that play important roles in egg development. A thorough characterization of egg protein expression throughout development is essential for understanding tick embryogenesis and for screening candidate molecules to develop novel interventions. In this study, eggs at four developmental stages (0, 7, 14, and 21 incubation days) were collected, and their protein extraction was profiled using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). On the first day of egg protein extraction, protein bands from day-1 eggs were re-collected and subsequently analyzed using liquid chromatography–tandem mass spectrometry (LC-MS/MS). The dynamic changes in forty egg proteins during development were further investigated using LC-parallel reaction monitoring (PRM)/MS analysis. A total of 108 transcripts were detected in day-1 eggs. Based on protein functions and families, these transcripts were classified into eight categories: transporters, enzymes, immunity and antimicrobial proteins, proteinase inhibitors, cytoskeletal proteins, heat shock proteins, secreted proteins, and uncharacterized proteins. Identification of the protein bands revealed that nine bands predominantly consisted of vitellogenin and vitellin-A, while other notable proteins included cathepsins and Kunitz domain-containing proteins. LC-PRM/MS analysis indicated that 28 transcripts increased significantly in abundance, including 13/18 enzymes, 1/1 antimicrobial peptide, 2/2 neutrophil elastase inhibitors, 3/4 vitellogenins, 3/3 heat shock proteins, 3/3 cytoskeletal proteins, 1/1 elongation factor-1, and 1/1 uncharacterized protein. Conversely, five transcripts showed a decrease significantly, including 1/1 Kunitz domain-containing protein, 2/6 aspartic proteases, and 2/5 serpins. This research provides a comprehensive overview of egg proteins and highlights the dynamic changes in protein expression during embryonic development, which may be pivotal for understanding protein functions and selecting potential candidates for further study. Full article

Plant aspartic proteinases (APs) from Cynara cardunculus feature unique plant-specific insert (PSI) domains, which serve as essential vacuolar sorting determinants, mediating the transport of proteins to the vacuole. Although their role in vacuolar trafficking is well established, the exact molecular mechanisms that regulate PSI interactions and functions remain largely unknown. This study explores the ability of PSI A and PSI B to form homo- and heterodimers using a combination of pull-down assays, the mating-based split-ubiquitin system (mbSUS), and FRET-FLIM analyses. Pull-down assays provided preliminary evidence of potential PSI homo- and heterodimer formation. This was conclusively validated by the more robust in vivo mbSUS and FRET-FLIM assays, which clearly demonstrated the formation of both homo- and heterodimers between PSI A and PSI B within cellular environments. These findings suggest that PSI dimerization is related to their broader functional role, particularly in protein trafficking. Results open new avenues for future research to explore the full extent of PSI dimerization and its implications in plant cellular processes. Full article

Background: Premature ovarian failure (POF) is a common disease among women, which can cause many complications and seriously threaten women’s physical and mental health. Currently, hormone replacement therapy is the primary treatment for premature ovarian failure. However, the side effects are serious and will increase the chance of breast cancer and endometrial cancer. Deer blood hydrolysate (DBH) is the product of enzymatic hydrolysis of deer blood, has antioxidant, anti-ageing, and anti-fatigue effects, and has the potential to improve premature ovarian failure. Methods: In our experiment, a mouse model of premature ovarian failure was established through intraperitoneal injection of 400 mg/kg/d of D-gal for 42 days. At the same time, different doses of DBH were gavaged to observe its ameliorative effect on premature ovarian failure. Results: The experimental findings indicated that DBH could restore the irregular oestrus cycle of POF mice, improve the abnormal amounts in serum hormones follicle-stimulating hormone (FSH), luteinising hormone (LH), progesterone (P) and estradiol (E2), increase the number of primordial follicles and decrease the number of atretic follicles. In addition, DBH also raised the level of superoxide dismutase (SOD) and reduced the level of malondialdehyde (MDA) and reduced the apoptosis of ovarian granulosa cells in mice. The WB assay results showed that gavage of DBH restored the decrease in the indication of nuclear factor erythroid 2-related factor 2 (Nrf2), Heme Oxygenase-1 (Ho-1), and B-cell lymphoma-2 (Bcl-2) proteins and reduced the elevated expression of Kelch-like ECH-associated protein 1 (Keap1), Bcl-2 associated X protein (Bax), and Cysteinyl aspartate specific proteinase-3 (Caspase-3) proteins that were induced by D-gal. Conclusions: To sum up, the present research indicated that DBH can ameliorate D-gal-induced oxidative stress and apoptosis by regulating the Nrf2/HO-1 signalling pathway and the Bcl-2/Bax/caspase-3 apoptosis pathway, which can be used for further development as a nutraceutical product to improve premature ovarian failure. Full article

Hexavalent chromium (Cr(VI)), a pervasive industrial contaminant, is highly toxic to both humans and animals. However, its effects on turtles are largely unexplored. Our study aimed to investigate the toxic effects of Cr(VI) on the Reeves’ turtles (Mauremys reevesii) primary hepatocytes. We exposed hepatocytes to two concentrations (25 μM and 50 μM) of Cr(VI) for 24 h. The results showed that compared to controls, Cr(VI)-treated cells showed elevated antioxidant enzyme activity (catalase (CAT) and superoxide dismutase (SOD)) and increased reactive oxygen species (ROS) levels. Adenosine triphosphatae (ATP) levels decreased, indicating mitochondrial dysfunction. Additionally, we found significant changes in mitochondrial dynamics related genes, with downregulation of mitofusin 2 (Mfn2) and silent information regulator 1 (SIRT1) and a decrease in sirtuin 3 (SIRT3) and tumor protein 53 (p53) mRNA levels. Annexin V-FITC fluorescence staining-positive cells increased with higher Cr(VI) concentrations, marked by elevated bcl-2-associated X protein (Bax) and cysteinyl aspartate specific proteinase (Caspase3) mRNA levels and reduced B-cell lymphoma-2 (Bcl2) expression. Autophagy-related genes were also affected, with increased microtubule-associated protein 1 light chain 3 (LC3-I), microtubule-associated protein light chain 3II (LC3-II), unc-51-like autophagy-activating kinase 1 (ULK1), and sequestosome 1 (p62/SQSTM1) mRNA levels and decreased mammalian target of rapamycin (mTOR) and Beclin1 expression. Taken together, Cr(VI) promotes cell apoptosis and autophagy in turtle hepatocytes by inducing oxidative stress and disrupting mitochondrial function. These findings highlight the serious health risks posed by Cr(VI) pollution and emphasize the need for protecting wild turtle populations. Full article

Safflower yellow is an extract of the famous Chinese medicine Carthamus tinctorious L, and safflower yellow injection (SYI) is widely used clinically to treat angina pectoris. However, there are few studies on the anti-myocardial ischemia/reperfusion (I/R) injury effect of SYI, and its mechanisms are unclear. In the present study, we aimed to investigate the protective effect of SYI on myocardial I/R injury and explore its underlying mechanisms. Male Sprague Dawley rats were randomly divided into a control group, sham group, model group, and SYI group (20 mg/kg, femoral vein injection 1 h before modeling). The left anterior descending coronary artery was ligated to establish a myocardial I/R model. H9c2 cells were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) after incubation with 80 μg/mL SYI for 24 h. In vivo, TsTC, HE, and TUNEL staining were performed to evaluate myocardial injury and apoptosis. A kit was used to detect superoxide dismutase (SOD) and malondialdehyde (MDA) to assess oxidative stress. In vitro, flow cytometry was used to detect the reactive oxygen species (ROS) content and apoptosis rate. Protein levels were determined via Western blotting. Pretreatment with SYI significantly reduced infarct size and pathological damage in rat hearts and suppressed cardiomyocyte apoptosis in vivo and in vitro. In addition, SYI inhibited oxidative stress by increasing SOD activity and decreasing MDA content and ROS production. Myocardial I/R and OGD/R activate endoplasmic reticulum (ER) stress, as evidenced by increased expression of activating transcription factor 6 (ATF6), glucose-regulated protein 78 (GRP78), cysteinyl aspartate-specific proteinase caspase-12, and C/EBP-homologous protein (CHOP), which were all inhibited by SYI. SYI ameliorated myocardial I/R injury by attenuating apoptosis, oxidative damage, and ER stress, which revealed new mechanistic insights into its application. Full article