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P/TGMS (Photo/thermo-sensitive genic male sterile) lines are crucial resources for two-line hybrid rice breeding. Previous studies revealed that slow development is a general mechanism for sterility-fertility conversion of P/TGMS in Arabidopsis. However, the difference in P/TGMS genes between rice and Arabidopsis suggests the presence of a distinct P/TGMS mechanism in rice. In this study, we isolated a novel P/TGMS line, ostms19, which shows sterility under high-temperature conditions and fertility under low-temperature conditions. OsTMS19 encodes a novel pentatricopeptide repeat (PPR) protein essential for pollen formation, in which a point mutation GTA(Val) to GCA(Ala) leads to ostms19 P/TGMS phenotype. It is highly expressed in the tapetum and localized to mitochondria. Under high temperature or long-day photoperiod conditions, excessive ROS accumulation in ostms19 anthers during pollen mitosis disrupts gene expression and intine formation, causing male sterility. Conversely, under low temperature or short-day photoperiod conditions, ROS can be effectively scavenged in anthers, resulting in fertility restoration. This indicates that ROS homeostasis is critical for fertility conversion. This relationship between ROS homeostasis and fertility conversion has also been observed in other tested rice P/TGMS lines. Therefore, we propose that ROS homeostasis is a general mechanism for the sterility-fertility conversion of rice P/TGMS lines.

Respiratory chain dysfunction can decrease ATP and increase reactive oxygen species (ROS) levels. Despite the importance of these metabolic parameters to a wide range of cellular functions and disease, we lack an integrated understanding of how they are differentially regulated. To address this question, we adapted a CRISPRi- and FACS-based platform to compare the effects of respiratory gene knockdown on ROS to their effects on ATP. Focusing on genes whose knockdown is known to decrease mitochondria-derived ATP, we showed that knockdown of genes in specific respiratory chain complexes (I, III, and CoQ10 biosynthesis) increased ROS, whereas knockdown of other low ATP hits either had no impact (mitochondrial ribosomal proteins) or actually decreased ROS (complex IV). Moreover, although shifting metabolic conditions profoundly altered mitochondria-derived ATP levels, it had little impact on mitochondrial or cytosolic ROS. In addition, knockdown of a subset of complex I subunits-including NDUFA8, NDUFB4, and NDUFS8-decreased complex I activity, mitochondria-derived ATP, and supercomplex level, but knockdown of these genes had differential effects on ROS. Conversely, we found an essential role for ether lipids in the dynamic regulation of mitochondrial ROS levels independent of ATP. Thus, our results identify specific metabolic regulators of cellular ATP and ROS balance that may help dissect the roles of these processes in disease and identify therapeutic strategies to independently target energy failure and oxidative stress.

Dielectric barrier discharge (DBD) plasma regulates the levels of reactive oxygen species (ROS), which are critical for sperm quality. MicroRNAs (miRNAs) are non-coding single-stranded RNA molecules encoded by endogenous genes, which regulate post-transcriptional gene expression in animals. At present, it is unknown whether DBD plasma can regulate sperm ROS levels through miRNAs. To further understand the regulatory mechanism of DBD plasma on sperm ROS levels, miRNAs in fresh boar spermatozoa were detected using Illumina deep sequencing technology. We found that 25 known miRNAs and 50 novel miRNAs were significantly upregulated, and 14 known miRNAs and 74 novel miRNAs were significantly downregulated in DBD plasma-treated spermatozoa. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that target genes of differentially expressed miRNAs were involved in many activities and pathways associated with antioxidants. We verified that DBD plasma significantly increased boar sperm quality and reduced ROS levels. These results suggest that DBD plasma can improve sperm quality by regulating ROS levels via miRNAs. Our findings provide a potential strategy to improve sperm quality through miRNA-targeted regulation of ROS, which helps to increase male reproduction and protect cryopreserved semen in clinical practice. • DBD plasma improves boar sperm quality by regulating ROS levels. • DBD plasma affects sperm ROS levels via differentially expressed miRNAs. • DBD plasma regulates sperm ROS levels via miRNA-targeted antioxidant enzyme genes. • DBD plasma regulates sperm ROS levels via miRNAs targeting the KEAP1/NRF2 pathway. [ABSTRACT FROM AUTHOR]

Plumbagin (PLB), a naphthoquinone compound, has been proven to have anti-cancer properties in different types of cancers. However, the anti-tumor actions as well as molecular processes in osteosarcoma (OS) remain unclear. This study investigates the underlying mechanisms of PLB in human OS cells in vitro. Our study showed that PLB significantly inhibited the proliferation of human OS cells in a time- and dosage-dependent manner. RNA sequencing data revealed that the efficacy of PLB is related to cell cycle, cell death, and p38 MAPK signaling pathway in KHOS-240S cells. Further studies indicated that PLB triggers G2/M phase arrest, mitochondrial-dependent apoptosis, as well as ferroptosis in human OS cells. Mechanistically, PLB treatment increased ROS generation that activates the p38 MAPK signaling pathway. BIRB 796, a p38 MAPK inhibitor, partly reversed PLB-induced phase arrest of G2/M and cell death. Furthermore, N-acetylcysteine (NAC), a ROS scavenger, significantly decreased G2/M phase arrest and cell death and reversed p38 MAPK activation caused by PLB. In conclusion, PLB induces arrest G2/M arrest, apoptosis as well as ferroptosis in human OS cells via ROS generation and p38 MAPK activation. There is potential for PLB to be an effective treatment for OS. • PLB induces G2/M arrest, apoptosis, and ferroptosis in human osteosarcoma cells. • The anti-osteosarcoma effect of Plumbagin is related to the ROS/p38 MAPK pathway. • PLB could be a promising therapeutic agent for osteosarcoma. [ABSTRACT FROM AUTHOR]

Skeletal muscle is a highly heterogeneous tissue, and its contractile proteins are composed of different isoforms, forming various types of muscle fiber, each of which has its own metabolic characteristics. It has been demonstrated that endurance exercise induces the transition of muscle fibers from fast-twitch to slow-twitch muscle fiber type. Herein, we discover a novel epigenetic mechanism for muscle contractile property tightly coupled to its metabolic capacity during muscle fiber type transition with exercise training. Our results show that an 8-week endurance exercise induces histone methylation remodeling of PGC-1α and myosin heavy chain (MHC) isoforms in the rat gastrocnemius muscle, accompanied by increased mitochondrial biogenesis and an elevated ratio of slow-twitch to fast-twitch fibers. Furthermore, to verify the roles of reactive oxygen species (ROS) and AMPK in exercise-regulated epigenetic modifications and muscle fiber type transitions, mouse C2C12 myotubes were used. It was shown that rotenone activates ROS/AMPK pathway and histone methylation enzymes, which then promote mitochondrial biogenesis and MHC slow isoform expression. Mitoquinone (MitoQ) partially blocking rotenone-treated model confirms the role of ROS in coupling mitochondrial biogenesis with muscle fiber type. In conclusion, endurance exercise couples mitochondrial biogenesis with MHC slow isoform by remodeling histone methylation, which in turn promotes the transition of fast-twitch to slow-twitch muscle fibers. The ROS/AMPK pathway may be involved in the regulation of histone methylation enzymes by endurance exercise. [ABSTRACT FROM AUTHOR]

Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC–MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a well-documented risk factor of intervertebral disc degeneration (IVDD). The current study was aimed to clarify the effects and mechanisms of NADH: ubiquinone oxidoreductase subunit A3 (NDUFA3) in human nucleus pulposus cells (HNPCs) exposed to high glucose. NDUFA3 was overexpressed in HNPCs via lenti-virus transduction, which were co-treated with high glucose and rotenone (a mitochondrial complex I inhibitor) for 48 h. Cell activities were assessed for cell viability, cell apoptosis, reactive oxygen species (ROS) production, mitochondrial membrane potential (MMP) ratio, oxygen consumption rate (OCR) and mitochondrial complexes I activities. High glucose decreased cell viability, increased apoptotic cells, increased ROS production, decreased MMP levels and OCR values in HNPCs in a dose-dependent manner. Rotenone co-treatment augmented the high glucose-induced injuries on cell viability, apoptosis, ROS production and mitochondrial function. NDUFA3 overexpression counteracted the high glucose-induced injuries in HNPCs. HDAC/H3K27ac mechanism was involved in regulating NDUFA3 transcription. NDUFA3 knockdown decreased cell viability and increased apoptotic cells, which were reversed by ROS scavenger N-acetylcysteine. HDAC/H3K27ac-mediated transcription of NDUFA3 protects HNPCs against high glucose-induced injuries through suppressing cell apoptosis, eliminating ROS, improving mitochondrial function and oxidative phosphorylation. This study sheds light on candidate therapeutic targets and deepens the understanding of molecular mechanisms behind DM-induced IVDD. [ABSTRACT FROM AUTHOR]

Human Papillomavirus (HPV), a prevalent sexually transmitted infection, comprises high-risk (HR-HPV) and low-risk (LR-HPV) viruses, the former posing a high risk for developing malignancies whereas the latter mainly for benign warts. Despite increasing awareness of HPV's impact on men's health, the influence of HR-HPV and LR-HPV urogenital infections on male fertility potential remains uncertain. This study aimed to investigate whether male urogenital infection with HR- or LR-HPV associates with impaired sperm quality, oxidative stress, and inflammation. A total of 205 male patients attending an urology clinic were enrolled. Semen samples were analyzed for HPV using PCR and genotyped by RFLP. Semen quality was evaluated following WHO guidelines. Semen leukocytes, reactive oxygen species (ROS), and sperm viability were analyzed using flow cytometry. HPV was detected in 19% (39/205) of semen samples. HR-HPV infections were more prevalent, with HPV-16 being the most frequent genotype. Neither HR-HPV nor LR-HPV were associated with significant alterations in routine sperm quality parameters. However, HR-HPV+ individuals showed significantly higher levels of sperm necrosis and exhibited increased proportions of ROS+ spermatozoa compared to LR-HPV+ or control individuals. Furthermore, no significant semen inflammation was detected in patients infected with either HR-HPV or LR-HPV, and unexpectedly reduced semen leukocytes and inflammatory cytokines (IL-6 and IL-1b) were observed in HR-HPV+ patients compared to controls. These observations underscore the importance of comprehensive HPV screening, including genotyping, in urology and fertility clinics to understand the progression of the infection, potential adverse effects on reproductive health, and the oncogenic risks involved. [ABSTRACT FROM AUTHOR]

Background: Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. Method: In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). Results: Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. Conclusion: Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development. [ABSTRACT FROM AUTHOR]

Eukaryotic cells respond to stress by altering coding and non‐coding gene expression programs. Alongside many approaches and regulatory mechanisms, long non‐coding RNAs (lncRNA) are finding a significant place in gene regulation, suggesting an involvement in various cellular processes and pathophysiology. LncRNAs are regulated by many transcription factors, including SMAR1 and p53, which are tumor suppressor genes. SMAR1 inhibits cancer cell metastasis and invasion and is also known to inhibit apoptosis during low‐dose stress in coordination with p53. Data mining analysis suggested that these tumor suppressor genes might coregulate the lncRNA RP11‐431M3.1 in colon cancer cells. Importantly, RP11‐431M3.1 expression was found to be negatively correlated with patient survival rates in a number of cancers. Oxidative stress occurs when an imbalance in the body is caused by reactive oxygen species (ROS). This imbalance is known to be important in the development/pathogenesis of colon cancer. We are researching the role and control of this lncRNA in HCT116 cells under conditions of oxidative stress. We observed a dose‐dependent differential expression of lncRNA upon H2O2 treatment and found that p53 and SMAR1 bind differentially to the promoter in response to the dose of stress inducer used. RP11‐431M3.1 was observed to sponge miR‐138 which has an important target gene, hypoxia‐inducible factor (HIF1A). miR‐138 was observed to bind differentially to RP11‐431M3.1 and HIF1A RNA depending on the dose of oxidative stress. Furthermore, the knockdown of RP11‐431M3.1 decreased the migration and proliferation of colon cancer cells. Our results suggest a previously undescribed regulatory mechanism through which RP11‐431M3.1 is transcriptionally regulated by SMAR1 and p53, target HIF1A through miR‐138, and highlight its potential as a therapeutic and diagnostic marker for cancer. [ABSTRACT FROM AUTHOR]

Sclerotinia sclerotiorum (Lib.) de Bary is the causative agent of stem white mold disease which severely reduces major crop productivity including soybean and rapeseed worldwide. The current study aimed to explore plant growth-promoting traits and biocontrol of new isolated Bacillus subtilis BS-2301 to suppress S. sclerotiorum through various mechanisms. The results indicated that the BS-2301 exhibited strong biocontrol potential against S. sclerotiorum up to 74% both in dual culture and partition plate experiments. The BS-2301 and its crude extract significantly suppressed S. sclerotiorum growth involving excessive reactive oxygen species (ROS) production in mycelia for rapid death. Furthermore, the treated hyphae produced low oxalic acid (OA), a crucial pathogenicity factor of S. sclerotiorum. The SEM and TEM microscopy of S. sclerotiorum showed severe damage in terms of cell wall, cell membrane breakage, cytoplasm displacement, and organelles disintegration compared to control. The pathogenicity of S. sclerotiorum exposed to BS-2301 had less disease progression potential on soybean leaves in the detached leaf assay experiment. Remarkably, the strain also demonstrated broad-range antagonistic activity with 70%, and 68% inhibition rates against Phytophthora sojae and Fusarium oxysporum, respectively. Furthermore, the strain exhibits multiple plant growth-promoting and disease-prevention traits, including the production of indole-3-acetic acid (IAA), siderophores, amylases, cellulases and proteases as well as harboring calcium phosphate decomposition activity. In comparison to the control, the BS-2301 also showed great potential for enhancing soybean seedlings growth for different parameters, including shoot length 31.23%, root length 29.87%, total fresh weight 33.45%, and total dry weight 27.56%. The antioxidant enzymes like CAT, POD, SOD and APX under BS-2301 treatment were up-regulated in S. sclerotiorum infected plants along with the positive regulation of defense-related genes (PR1-2, PR10, PAL1, AOS, CHS, and PDF1.2). These findings demonstrate that the BS-2301 strain possesses a notable broad-spectrum biocontrol potential against different phytopathogens and provides new insight in suppressing S. sclerotiorum through various mechanisms. Therefore, BS-2301 will be helpful in the development of biofertilizers for sustainable agricultural practices. [ABSTRACT FROM AUTHOR]

Global warming is a leading environmental stress that reduces plant productivity worldwide. Several beneficial microorganisms reduce stress; however, the mechanism by which plant–microbe interactions occur and reduce stress remains to be fully elucidated. The aim of the present study was to elucidate the mutualistic interaction between the plant growth-promoting rhizobacterial strain SH-19 and soybeans of the Pungsannamul variety. The results showed that SH-19 possessed several plant growth-promoting traits, such as the production of indole-3-acetic acid, siderophore, and exopolysaccharide, and had the capacity for phosphate solubilisation. The heat tolerance assay showed that SH-19 could withstand temperatures up to 45 °C. The strain SH-19 was identified as P. megaterium using the 16S ribosomal DNA gene sequence technique. Inoculation of soybeans with SH-19 improved seedling characteristics under high-temperature stress. This may be due to an increase in the endogenous salicylic acid level and a decrease in the abscisic acid level compared with the negative control group. The strain of SH-19 increased the activity of the endogenous antioxidant defense system, resulting in the upregulation of GSH (44.8%), SOD (23.1%), APX (11%), and CAT (52.6%). Furthermore, this study involved the transcription factors GmHSP, GmbZIP1, and GmNCED3. The findings showed upregulation of the two transcription factors GmbZIP1 (17%), GmNCED3 (15%) involved in ABA biosynthesis and induced stomatal regulation, similarly, a downregulation of the expression pattern of GmHSP by 25% was observed. Overall, the results of this study indicate that the strain SH-19 promotes plant growth, reduces high-temperature stress, and improves physiological parameters by regulating endogenous phytohormones, the antioxidant defense system, and genetic expression. The isolated strain (SH-19) could be commercialized as a biofertilizer. [ABSTRACT FROM AUTHOR]

Ginseng, from the roots of Panax ginseng C. A. Meyer, is a widely used herbal medicine in Asian countries, known for its excellent therapeutic properties. The growth of P. ginseng is depend on specific and strict environments, with a preference for wetness but intolerance for flooding. Under excessive soil moisture, some irregular rust-like substances are deposited on the root epidermis, causing ginseng rusty symptoms (GRS). This condition leads to a significant reduce in yield and quality, resulting in substantial economic loses. However, there is less knowledge on the cause of GRS and there are no effective treatments available for its treatment once it occurs. Unsuitable environments lead to the generation of large amounts of reactive oxygen species (ROS). We investigated the key indicators associated with the stress response during different physiological stages of GRS development. We observed a significant change in ROS level, MDA contents, antioxidant enzymes activities, and non-enzymatic antioxidants contents prior to the GRS. Through the analysis of soil features with an abundance of moisture, we further determined the source of ROS. The levels of nitrate reductase (NR) and nitric oxide synthase (NOS) activities in the inter-root soil of ginseng with GRS were significantly elevated compared to those of healthy ginseng. These enzymes boost nitric oxide (NO) levels, which in turn showed a favorable correlation with the GRS. The activities of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase first rose and then decreased as GRS developed. Excess soil moisture causes a decrease in oxygen levels. This activated NR and NOS in the soil, resulting in a production of excess NO. The NO then diffused into the ginseng root and triggered a burst of ROS through NADPH located on the cell membrane. Additionally, Fe2+ in soil was oxidized to red Fe3+, and finally led to GRS. This conclusion was also verified by the Sodium Nitroprusside (SNP), a precursor compound producing NO. The presence of NO from NR and NOS in water-saturated soil is responsible for the generation of ROS. Among these, NO is the main component that contribute to the occurrence of GRS. [ABSTRACT FROM AUTHOR]

Background: Polystyrene nanoplastics (PS-NPs) are becoming increasingly prevalent in the environment with great advancements in plastic products, and their potential health hazard to animals has received much attention. Several studies have reported the toxicity of PS-NPs to various tissues and cells; however, there is a paucity of information about whether PS-NPs exposure can have toxic effects on mammalian oocytes, especially livestock. Herein, porcine oocytes were used as the model to investigate the potential effects of PS-NPs on mammalian oocytes. Results: The findings showed that different concentrations of PS-NPs (0, 25, 50 and 100 μg/mL) entering into porcine oocytes could induce mitochondrial stress, including a significant decrease in mitochondrial membrane potential (MMP), and the destruction of the balance of mitochondrial dynamic and micromorphology. Furthermore, there was a marked increase in reactive oxygen species (ROS), which led to oocyte lipid peroxidation (LPO). PS-NPs exposure induced abnormal intracellular iron overload, and subsequently increased the expression of transferrin receptor (TfRC), solute carrier family 7 member 11 (SLC7a11), and acyl-CoA synthetase long-chain family member 4 (ACSL4), which resulted in ferroptosis in oocytes. PS-NPs also induced oocyte maturation failure, cytoskeletal dysfunction and DNA damage. Cotreatment with 5 μmol/L ferrostatin-1 (Fer-1, an inhibitor of ferroptosis) alleviated the cellular toxicity associated with PS-NPs exposure during porcine oocyte maturation. Conclusions: In conclusion, PS-NPs caused ferroptosis in porcine oocytes by increasing oxidative stress and altering lipid metabolism, leading to the failure of oocyte maturation. PS-NPs could enter oocytes, caused mitochondrial dysfunction and oxidative stress, induced lipid peroxidation and ferroptosis, which eventually resulted in failure of oocyte maturation. [ABSTRACT FROM AUTHOR]

Oxygen (O2) metabolism plays a critical role in cornea wound healing, regeneration, and homeostasis; however, the underlying spatiotemporal mechanisms are poorly understood. Here we used an optical sensor to profile O2 flux in intact and wounded corneas of mouse eyes. Intact corneas have unique centrifugal O2 influx profiles, smallest flux at the cornea center, and highest at the limbus. Following cornea injury, the O2 influx profile presents three distinct consecutive phases: a "decreasing" phase from 0 to 6 h, a "recovering" phase from 12 to 48 h, and a 'peak' phase from 48 to 72 h, congruent to previously described healing phases. Immediately after wounding, the O2 influx drops at wound center and wound edge but does not change significantly at the wound side or limbus. Inhibition of reactive oxygen species (ROS) in the decreasing phase significantly reduces O2 influx, decreases epithelial migration and consequently delays healing. The dynamics of O2 influx show a positive correlation with cell proliferation at the wound side, with significantly increased proliferation at the peak phase of O2 influx. This study elucidates the spatiotemporal O2 dynamics in both intact and wounded rodent cornea and shows the crucial role of O2 dynamics in regulating cell migration and proliferation through ROS metabolism, ultimately contributing to wound healing. These results demonstrate the usefulness of the micro‐optrode in the characterization of spatiotemporal O2 dynamics. Injury‐induced changes in O2 metabolism and ROS production modulate O2 dynamics at wound and control cell migration and proliferation, both essential for proper wound healing. [ABSTRACT FROM AUTHOR]

Pollen grains are central to sexual plant reproduction and their viability and longevity/storage are critical for plant physiology, ecology, plant breeding, and many plant product industries. Our goal is to present progress in assessing pollen viability/longevity along with recent advances in our understanding of the intrinsic and environmental factors that determine pollen performance: the capacity of the pollen grain to be stored, germinate, produce a pollen tube, and fertilize the ovule. We review current methods to measure pollen viability, with an eye toward advancing basic research and biotechnological applications. Importantly, we review recent advances in our understanding of how basic aspects of pollen/stigma development, pollen molecular composition, and intra- and intercellular signaling systems interact with the environment to determine pollen performance. Our goal is to point to key questions for future research, especially given that climate change will directly impact pollen viability/longevity. We find that the viability and longevity of pollen are highly sensitive to environmental conditions that affect complex interactions between maternal and paternal tissues and internal pollen physiological events. As pollen viability and longevity are critical factors for food security and adaptation to climate change, we highlight the need to develop further basic research for better understanding the complex molecular mechanisms that modulate pollen viability and applied research on developing new methods to maintain or improve pollen viability and longevity. [ABSTRACT FROM AUTHOR]

Cold physical plasma, a partially ionized gas, has been shown to be effective in treating chronic wounds and cancer. However, there is limited research on plasma exposure of leukemia cell lines, such as chronic lymphocytic leukemia (CLL) and cytotoxic CD8+ T cells. To investigate the potential proimmunogenic effects of plasma‐derived reactive oxygen species, cytotoxic T cells were isolated from CLL patients and healthy volunteers. Extensive cold plasma treatment reduced T‐cell metabolic activity and viability in both diseased and healthy groups. Plasma treatment of cocultures, but not CD8+ T‐cell monocultures, spurred cytotoxic T‐cell proliferation, possibly due to plasma‐enhanced CLL antigen display and plasma‐mediated modulation of immunoregulatory surface molecules. Further studies are needed to understand the mechanisms and clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

Proton pump inhibitors (PPIs) are one of the most commonly prescribed medications. However, PPI usage is linked to a higher risk of both acute and chronic renal damage by mechanisms not entirely known. The present study demonstrates that omeprazole (10 mg/kg body weight, i.p.) causes TGF-β/Smad signaling activation and subsequent expression of the profibrotic genes CTGF and TIMP-1 in rat kidney. Increased production of CTGF and TIMP-1 accompany activation of the TGF-β/Smad signaling cascade. However, simultaneous treatment of omeprazole and the TGF-β inhibitor, disitertide (P144) (1 mg/kg body weight i.p.) suppresses the TGF-β/Smad signaling pathway and subsequent production of CTGF and TIMP-1. Additionally, TGF-β level in rat kidney was highly reduced in animals treated with the ROS (reactive oxygen species) scavenger, N-acetyl cysteine (NAC) (100 mg/kg body weight i.p.) before omeprazole administration. Furthermore, the reduction in SOD activity brought by omeprazole was returned to the normal level in those animals. However, MDA level increased by omeprazole was highly reduced in the presence of NAC. Collectively, the current findings demonstrate that omeprazole has the ability to promote the expression of the profibrotic genes CTGF and TIMP-1 in a ROS and TGF-β dependent manner. The present study suggests the co-use of ROS scavenger to improve the therapeutic use of the PPI omeprazole. [ABSTRACT FROM AUTHOR]

Chlorpyrifos (CPF) is a widely used pesticide that can impair body organs. Nonetheless, metformin is known for its protective role against dysfunction at cellular and molecular levels led by inflammatory and oxidative stress. This study aimed to investigate the modulatory impacts of metformin on CPF-induced heart and lung damage. Following the treatment of Wistar rats with different combinations of metformin and CPF, plasma, as well as heart and lung tissues, were isolated to examine the level of oxidative stress biomarkers like reactive oxygen species (ROS) and malondialdehyde (MDA), inflammatory cytokines such as tumor necrosis alpha (TNF-α), high mobility group box 1 (HMGB1) gene, deoxyribonucleic acid (DNA) damage, lactate, ADP/ATP ratio, expression of relevant genes (TRADD, TERT, KL), and along with histological analysis. Based on the findings, metformin significantly modulates the impairments in heart and lung tissues induced by CPF. [ABSTRACT FROM AUTHOR]

Cellular responses to hypoxia are crucial in various physiological and pathophysiological contexts and have thus been extensively studied. This has led to a comprehensive understanding of the transcriptional response to hypoxia, which is regulated by hypoxia-inducible factors (HIFs). However, the detailed molecular mechanisms of HIF regulation in hypoxia remain incompletely understood. In particular, there is controversy surrounding the production of mitochondrial reactive oxygen species (ROS) in hypoxia and how this affects the stabilization and activity of HIFs. This review examines this controversy and attempts to shed light on its origin. We discuss the role of physioxia versus normoxia as baseline conditions that can affect the subsequent cellular response to hypoxia and highlight the paucity of data on pericellular oxygen levels in most experiments, leading to variable levels of hypoxia that might progress to anoxia over time. We analyze the different outcomes reported in isolated mitochondria, versus intact cells or whole organisms, and evaluate the reliability of various ROS-detecting tools. Finally, we examine the cell-type and context specificity of oxygen's various effects. We conclude that while recent evidence suggests that the effect of hypoxia on ROS production is highly dependent on the cell type and the duration of exposure, efforts should be made to conduct experiments under carefully controlled, physiological microenvironmental conditions in order to rule out potential artifacts and improve reproducibility in research. [ABSTRACT FROM AUTHOR]

As a prevalent neurodegenerative disorder, Parkinson's disease is associated with oxidative stress. Our recent investigations revealed that reactive oxygen species (ROS) and PD-toxins like 6-hydroxydopamine (6-OHDA) can induce neuronal apoptosis through over-activation of Akt signaling. Chlorogenic acid (CGA), a natural acid phenol abundant in the human diet, is well-documented for its ability to mitigate intracellular ROS. In this study, we utilized CGA to treat experimental models of PD both in vitro and in vivo. Our study results demonstrated that SH-SY5Y and primary neurons exhibited cell apoptosis in response to 6-OHDA. Pretreatment with CGA significantly attenuated PD toxins-induced large amount of ROS, inhibiting Erk1/2 activation, preventing Akt inhibition, and hindering neuronal cell death. Combining the Erk1/2 inhibitor U0126 with CGA could reverse 6-OHDA-induced Akt inhibition, ROS, and apoptosis in the cells. Crucially, the Akt activator SC79 and ROS scavenger NAC both could eliminate excessive ROS via Akt and Erk1/2 signaling pathways, and CGA further potentiated these effects in PD models. Behavioral experiments revealed that CGA could alleviate gait abnormalities in PD model mice. The neuroprotective effects have been demonstrated in several endocrine regions and in the substantia nigra tissue, which shows the positive tyrosine hydroxylase (TH). Overall, our results suggest that CGA prevents the activation of Erk1/2 and inactivation of Akt by removing excess ROS in PD models. These findings propose a potential strategy for mitigating neuronal degeneration in Parkinson's disease by modulating the Akt/Erk1/2 signaling pathway through the administration of CGA and/or the use of antioxidants to alleviate oxidative stress. • CGA effectively mitigates the axonal damage induced by 6-OHDA in neuronal cells. • CGA inhibits excessive ROS production via the AKT/Erk1/2 signal pathway, preventing 6-OHDA-induced neuronal apoptosis. • CGA ameliorates dyskinesia of the A53T mice. • CGA mitigates the neuronal apoptosis and the histopathologic aberrations via the AKT/Erk1/2 signal pathway in the A53T mice. [ABSTRACT FROM AUTHOR]

Summary: Climate warming poses a significant threat to global crop production and food security. However, our understanding of the molecular mechanisms governing thermoresponsive development in crops remains limited.Here we report that the auxiliary subunit of N‐terminal acetyltransferase A (NatA) in rice OsNAA15 is a prerequisite for rice thermoresponsive growth. OsNAA15 produces two isoforms OsNAA15.1 and OsNAA15.2, via temperature‐dependent alternative splicing. Among the two, OsNAA15.1 is more likely to form a stable and functional NatA complex with the potential catalytic subunit OsNAA10, leading to a thermoresponsive N‐terminal acetylome. Intriguingly, while OsNAA15.1 promotes plant growth under elevated temperatures, OsNAA15.2 exhibits an inhibitory effect.We identified two glycolate oxidases (GLO1/5) as major substrates from the thermoresponsive acetylome. These enzymes are involved in hydrogen peroxide (H2O2) biosynthesis via glycolate oxidation. N‐terminally acetylated GLO1/5 undergo their degradation through the ubiquitin‐proteasome system. This leads to reduced reactive oxygen species (ROS) production, thereby promoting plant growth, particularly under high ambient temperatures.Conclusively, our findings highlight the pivotal role of N‐terminal acetylation in orchestrating the glycolate‐mediated ROS homeostasis to facilitate thermoresponsive growth in rice. [ABSTRACT FROM AUTHOR]

• Sesamum indicum , a commercial oilseed crop shows less productivity during severe and recurrent drought exposure. But its wild relative S. radiatum is considered as a potential candidate for drought-resistance. • Upon exposure to drought (15 days), the wild taxa sustained cellular turgor, regulated lipid peroxidation through enhanced accumulation of osmolytes, and higher activity of antioxidants than the cultivar. • The wild taxa recovered at a faster rate upon rewatering, and can be used to improve the drought-tolerance of sesame, thereby to combat the forthcoming climate crisis. Drought is one of the most significant abiotic stresses that affect plant performance, lowers agricultural output, and, in extreme cases, results in crop loss. The major challenge faced by farmers is to ensure the production of crop varieties under extreme environmental conditions. Sesame (Sesamum indicum L.) is a traditionally important major cash crop for small and marginal farmers in some developing countries since it requires less intensive care and investment. Although sesame is considered as a resilient crop, it remains sensitive to severe drought. In this study, the morpho-physiological, biochemical, and antioxidant responses of wild and cultivar species of Sesamum viz., S. radiatum , and S. indicum subjected to different irrigation treatments such as mild (75 % Field capacity), moderate (50 % FC) and severe (25 % FC) drought and subsequent recovery (rewatered to 100 % FC) were evaluated in comparison with control groups. Present findings revealed that both species displayed differential responses to the drought stress and subsequent recovery. In particular, the wild taxa demonstrated better drought tolerance, probably due to their higher leaf-relative water content, decreased lipid peroxidation, enhanced accumulation of osmolytes, and increased activities of enzymatic and non-enzymatic antioxidants. On the other hand, the cultivar presented reduced leaf-relative water content, increased lipid peroxidation, higher electrolyte leakage, and reduced antioxidant activities, mostly at 25 % FC. Present data suggests that the cultivar was strictly exacerbated, mostly during severe water deficits; however, the wild species could re-adjust to the water deficit circumstances and recover completely. The current study implies the potential of wild species that can be used to improve the drought tolerance of commercial sesame by utilizing the same in breeding programs. [ABSTRACT FROM AUTHOR]

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66–24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans. [ABSTRACT FROM AUTHOR]

Superoxide dismutase (SOD) is a crucial enzyme responsible for the redox homeostasis inside the cell. As a part of the antioxidant defense system, it plays a pivotal role in the dismutation of the superoxide radicals (O2−) generated mainly by the oxidative phosphorylation, which would otherwise bring out the redox dysregulation, leading to higher reactive oxygen species (ROS) generation and, ultimately, cell transformation, and malignancy. Several studies have shown the involvement of ROS in a wide range of human cancers. As SOD is the key enzyme in regulating ROS, any change, such as a transcriptional change, epigenetic remodeling, functional alteration, and so forth, either activates the proto‐oncogenes or aberrant signaling cascades, which results in cancer. Interestingly, in some cases, SODs act as tumor promoters instead of suppressors. Furthermore, SODs have also been known to switch their role during tumor progression. In this review, we have tried to give a comprehensive account of SODs multifactorial role in various human cancers so that SODs‐based therapeutic strategies could be made to thwart cancers. [ABSTRACT FROM AUTHOR]

P38 mitogen‐activated protein kinases are key in the regulation of the cellular response to stressors. P38 is known to regulate transcription, mRNA processing, stability, and translation. The transcriptional changes mediated by phosphorylated p38 (P‐p38) in response to extracellular stimuli have been thoroughly analyzed in many tissues and organisms. However, the genomic localization of chromatin‐associated P‐p38 remains poorly understood. Here, we analyze the chromatin binding of activated P‐p38 and its role in the response to reactive oxygen species (ROS) in Drosophila S2 cells. We found that P‐p38 is already bound to chromatin in basal conditions. After ROS exposure, chromatin‐associated P‐p38 relocates towards genes involved in the recovery process. Our findings highlight the role of P‐p38 dynamic chromatin binding in orchestrating gene expression responses to oxidative stress. [ABSTRACT FROM AUTHOR]

Psoriasis, a chronic and easily recurring inflammatory skin disease, causes a great economic burden to the patient’s family because the etiology and mechanism are still unclear and the treatment cycle is long. In this study, the function and related mechanisms of Momordin Ic in psoriasis were investigated. The IMQ-induced mouse psoriasis model was constructed. The protective effects of different doses of Momordin Ic on psoriasis skin damage in mice were detected by PASI score, HE staining and Ki-67 staining. A psoriasis-like keratinocyte model was established at the cellular level using M5 (IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α) triggered HaCaT. The effects of Momordin Ic upon HaCaT cell biological behavior were examined using MTT and CCK-8 assays. In terms of mechanism, the expression level of each inflammatory factor was assessed using IHC staining and/or ELISA, qRT-PCR, the expression of oxidative stress-related indicators was detected biochemically, and western blot was performed to detect the levels of key proteins of the Wnt signaling and VEGF. As the results shown, at the in vivo level, Momordin Ic significantly alleviated skin damage, reduced PASI score and inhibited hyperproliferation of keratinized cells in psoriasis mice. At the cellular level, Momordin Ic also significantly reversed M5-induced hyperproliferation of HaCaT keratinocytes. In terms of mechanism, Momordin Ic significantly inhibited the IL-23/IL-17 axis, dramatically elevated the levels of intracellular antioxidants including SOD, GSH-Px, and CAT, and significantly down-regulated the levels of the indicator of oxidative damage, malondialdehyde (MDA). In addition, Momordin Ic also significantly inhibited the level of β-catenin, a pivotal protein of the Wnt signaling, C-Myc, a target gene of the Wnt signaling, and VEGF, a critical protein of angiogenesis. In conclusion, Momordin Ic can be involved in the skin-protective effects of psoriasis by multiple mechanisms, including inhibition of the Wnt signaling pathway and the IL-23/IL-17 axis, and suppression of oxidative damageand VEGF expression. Momordin Ic has been proven to be an underlying therapeutic drug for the treatment of psoriasis. [ABSTRACT FROM AUTHOR]

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The operational environments in which a mobile robot executes its missions often exhibit nonflat terrain characteristics, encompassing outdoor and indoor settings featuring ramps and slopes. In such scenarios, the conventional methodologies employed for localization encounter novel challenges and limitations. This study delineates a localization framework incorporating ground elevation and incline considerations, deviating from traditional two‐dimensional localization paradigms that may falter in such contexts. In our proposed approach, the map encompasses elevation and spatial occupancy information, employing Gridmaps and Octomaps. At the same time, the perception model is designed to accommodate the robot's inclined orientation and the potential presence of ground as an obstacle, besides usual structural and dynamic obstacles. We provide an implementation of our approach fully working with Nav2, ready to replace the baseline Adaptative Monte Carlo Localization (AMCL) approach when the robot is in nonplanar environments. Our methodology was rigorously tested in both simulated environments and through practical application on actual robots, including the Tiago and Summit XL models, across various settings ranging from indoor and outdoor to flat and uneven terrains. Demonstrating exceptional precision, our approach yielded error margins below 10 cm and 0.05 radians in indoor settings and less than 1.0 m in extensive outdoor routes. While our results exhibit a slight improvement over AMCL in indoor environments, the enhancement in performance is significantly more pronounced when compared to three‐dimensional simultaneous localization and mapping algorithms. This underscores the considerable robustness and efficiency of our approach, positioning it as an effective strategy for mobile robots tasked with navigating expansive and intricate indoor/outdoor environments. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is a promising cancer treatment. This study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[-diethylene triamine pentaacetic acid-aminophenyl]-10,15,20-triphenyl-porphyrin (DTP) mediated PDT (DTP-PDT). Cell viability, reactive oxygen species (ROS), and apoptosis were measured with a Cell Counting Kit-8 assay, DCFH-DA fluorescent probe, and Hoechst staining, respectively. Cell apoptosis- and autophagy-related proteins were examined using western blotting. RNA sequencing was used to screen differentially expressed mRNAs (DERs), and bioinformatic analysis was performed to identify the major biological events after DTP-PDT. Our results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 cells. The ROS scavenger N-acetyl-L-cysteine (NAC) and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced cytotoxicity. DTP-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2, which could also be inhibited by NAC or SB203580. The level of LC3B-II, a marker of autophagy, was increased by DTP-PDT. A total of 3496 DERs were obtained after DTP-PDT. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes, the nuclear lumen, protein binding, cell cycle, protein targeting to the endoplasmic reticulum, and ribosomal DNA replication. Disease Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle checkpoints. Protein-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting genes. Therefore, DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy, partly through ROS and the P38 MAPK signaling pathway. Genes associated with the cell cycle, ribosomes, DNA replication, and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

Bleomycin exhibits effective chemotherapeutic activity against multiple types of tumors, and also induces various side effects, such as pulmonary fibrosis and neuronal defects, which limit the clinical application of this drug. Macroautophagy/autophagy has been recently reported to be involved in the functions of bleomycin, and yet the mechanisms of their crosstalk remain insufficiently understood. Here, we demonstrated that reactive oxygen species (ROS) produced during bleomycin activation hampered autophagy flux by inducing lysosomal membrane permeabilization (LMP) and obstructing lysosomal degradation. Exhaustion of ROS with N-acetylcysteine relieved LMP and autophagy defects. Notably, we observed that LMP and autophagy blockage preceded the emergence of cellular senescence during bleomycin treatment. In addition, promoting or inhibiting autophagy-lysosome degradation alleviated or exacerbated the phenotypes of senescence, respectively. This suggests the alternation of autophagy activity is more a regulatory mechanism than a consequence of bleomycin-induced cellular senescence. Taken together, we reveal a specific role of bleomycin-induced ROS in mediating defects of autophagic degradation and further regulating cellular senescence in vitro and in vivo. Our findings, conversely, indicate the autophagy-lysosome degradation pathway as a target for modulating the functions of bleomycin. These provide a new perspective for optimizing bleomycin as a clinically applicable chemotherapeutics devoid of severe side-effects. Abbreviations: AT2 cells: type II alveolar epithelial cells; ATG7: autophagy related 7; bEnd.3: mouse brain microvascular endothelial cells; BNIP3L: BCL2/adenovirus E1B interacting protein 3-like; CCL2: C-C motif chemokine ligand 2; CDKN1A: cyclin dependent kinase inhibitor 1A; CDKN2A: cyclin dependent kinase inhibitor 2A; FTH1: ferritin heavy polypeptide 1; γ-H2AX: phosphorylated H2A.X variant histone; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HUVEC: human umbilical vein endothelial cells; HT22: hippocampal neuronal cell lines; Il: interleukin; LAMP: lysosomal-associated membrane protein; LMP: lysosome membrane permeabilization; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NCOA4: nuclear receptor coactivator 4; PI3K: phosphoinositide 3-kinase; ROS: reactive oxygen species; RPS6KB/S6K: ribosomal protein S6 kinase; SA-GLB1/β-gal: senescence-associated galactosidase, beta 1; SAHF: senescence-associated heterochromatic foci; SASP: senescence-associated secretory phenotype; SEC62: SEC62 homolog, preprotein translocation; SEP: superecliptic pHluorin; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB [ABSTRACT FROM AUTHOR]

The development of immersive technologies in recent years has facilitated the control and execution of tasks at a high level of complexity in robotic systems. On the other hand, exploration and manipulation tasks in unknown environments have been one of the main challenges in search and rescue (SAR) robotics. Due to the complexity and uncertainty involved in autonomous manipulation tasks in unstructured environments, these are usually tele-operated initially. This article addresses a comparative study between Mixed Reality (MR—Hololens) and Virtual Reality (VR—HTC-Vive) methods for teleoperating legged-manipulator robots in the context of search and rescue. For this purpose, a teleoperation robotics method was established to address the comparison, developing VR–MR interfaces with the same contextualization and operational functionality for mission management and robot control of a robotic set composed of a quadrupedal robot equipped with a 6 degrees of freedom (6DoF) manipulator, by a user using hand gestures. A set of metrics is proposed for the comparative evaluation of the interfaces considering parameters that allow analyzing operability in the context of the mission (latencies, physical parameters of the equipment, etc.), as well as from the aspect of operator performance (required training, confidence levels, etc.). The experimental phase was conducted using both on-site and remote operations to evaluate and categorize the advantages and disadvantages of each method. [ABSTRACT FROM AUTHOR]

We attempted to study the response of six rice cultivars, viz., BPT 5204, CR 1009, TRY 1, CO 50, Jodimattai, and CO 46, to salt stress under in vitro conditions. In this study, we report the highest relative growth rate (RGR) in BPT 5204 and TRY1, suggesting that these could maintain a higher relative fresh mass of the callus to survive salt stress. For regeneration frequency (RF), genotype TRY 1 registered the highest RF (35%) in the control (0 mM NaCl), but a significant reduction in RF (66%) was observed at 90, 120, and 150 mM NaCl. The genotypes CO 50, CR 1009, and BPT 5204 registered the lowest regeneration frequency (6.7%) and produced a moderate number of shoots. The biochemical nature of stress implies that proline content decreases in the control and progressively increases from 30 to 90 mM but gradually decreases with higher salt concentrations. The proline content was high for both tolerant (BPT 5204) and sensitive (CO-46) cultivars, implying that proline gives adaptiveness rather than growth. Our results provide unique insight into the antioxidant (catalase (CAT), ascorbate peroxidase (APX), and superoxide dismutase (SOD)) properties of callus culture. Antioxidants act as potential reactive oxygen species (ROS) scavengers and provide adaptive mechanisms to plants. The antioxidant enzyme activities increased progressively with increasing NaCl concentration in the medium, showing that antioxidants augment the stress and provide an adaptive mechanism. The genotypes BPT 5204 and TRY1 had a significant level of enzyme activities at 90, 120, and 150 mM NaCl treatment, whereas the other genotypes seemed to have reduced enzymatic activities. Hence, the genotypes BPT 5204 and TRY1 were better in their performance for the above parameters, which showed growth and biochemical homeostasis in response to salt stress. [ABSTRACT FROM AUTHOR]

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity. [ABSTRACT FROM AUTHOR]

The process of skin ageing is a natural biological phenomenon characterised by the emergence of wrinkles, age spots, sagging skin, and dryness over time. The increasing significance of skin in physical attractiveness has heightened skincare concerns. Anti-ageing cosmetics play a pivotal role in nurturing the skin, enhancing its quality, and promoting overall health. Today, cosmetics have evolved beyond mere aesthetics and are now integral to individual wellness. The contemporary quest for perpetual youth has intensified, prompting a deeper exploration into the skin ageing process. This comprehensive exploration delves into various elements involved in skin ageing, encompassing cells such as stem and endothelial cells, blood vessels, soft tissues, and signalling pathways. The molecular basis of skin ageing, including biochemical factors like reactive oxygen species, damaged DNA, free radicals, ions, and proteins (mRNA), is scrutinised alongside relevant animal models. The article critically analyzes the outcomes of utilising herbal components, emphasising their advantageous anti-ageing properties. The factors contributing to skin ageing, mechanistic perspectives, management approaches involving herbal cosmeceutical, and associated complications (especially cardiovascular diseases, Parkinson's, Alzheimer's, etc.) are succinctly addressed. In addition, the manuscript further summarises the recent patented innovations and toxicity of the herbal cosmeceuticals for anti-ageing and ageing associated disorders. Despite progress, further research is imperative to unlock the full potential of herbal components as anti-ageing agents. [ABSTRACT FROM AUTHOR]

Monosodium urate (MSU) crystallisation deposited in local tissues and organs induce inflammatory reactions, resulting in diseases such as gout. MSU has been recognized as a common and prevalent pathology in various clinical conditions. In this study, we investigated the role of MSU in the pathogenesis of diabetic kidney disease (DKD). We induced renal injury in diabetic kidney disease mice using streptozotocin (STZ) and assessed renal histopathological damage using Masson's trichrome staining and Collagen III immunofluorescence staining. We measured the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and uric acid (UA) using ELISA. Protein expression levels of NLRP3, p-NF-κB, SHP2, p-STAT3, and p-ERK1/2 were analyzed by Western blot. To further investigate the role of MSU in diabetic kidney disease, we conducted in vitro experiments. In our in vivo experiments, we found that compared to the Model group, there was a significant increase in interstitial fibrosis in the kidneys of mice after treatment with MSU, accompanied by elevated levels of MDA, SOD, and UA. Furthermore, the protein expression of NLRP3, p-NF-NB, SHP2, p-STAT3, and p-ERK1/2 was upregulated. In our subsequent studies on mouse fibroblasts (L929 cells), we discovered that high glucose, MSU, and TGF-β could promote the expression of P22, GP91, NLRP3, NF-κB, p-NF-κB, p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins. Additionally, we found that SHP2 could counteract the upregulation trend induced by MSU on the expression of p-SHP2, p-EGFR, p-STAT3, and Collagen-III proteins, and inhibitors YQ128, NAC, and Cetuximab exhibited similar effects. Furthermore, immunofluorescence results indicated that SHP2 could inhibit the expression of the fibrosis marker α-SMA in L929 cells. These findings suggest that MSU can promote renal fibroblast SHP2 expression, induce oxidative stress, activate the NLRP3/NF-κB pathway, and enhance diabetic kidney disease fibroblast proliferation through the TGFβ/STAT3/ERK1/2 signaling pathway, leading to renal fibrosis. [ABSTRACT FROM AUTHOR]

Anterior cruciate ligament (ACL) injuries pose a significant challenge due to their limited healing potential, often resulting in premature arthritis. The factors and mechanisms contributing to this inadequate healing process remain elusive. During the acute phase of injury, ACL tissues express elevated periostin levels that decline over time. The functional significance of periostin in ligament biology remains understudied. In this study, we investigated the functional and mechanistic implications of periostin deficiency in ACL biology, utilizing ligament fibroblasts derived from patients and a murine model of ACL rupture. Our investigations unveiled that periostin knockdown compromised fibroblast growth characteristics, hindered the egress of progenitor cells from explants, and arrested cell‐cycle progression, resulting in the accumulation of cells in the G0/G1 phase and moderate apoptosis. Concurrently, a significant reduction in the expression of cell‐cycle and matrix‐related genes was observed. Moreover, periostin deficiency triggered apoptosis through STAT3Y705/p38MAPK signaling and induced cellular senescence through increased production of reactive oxygen species (ROS). Mechanistically, inhibition of ROS production mitigated cell senescence in these cells. Notably, in vivo data revealed that ACL in Postn−/− mice exhibited a higher tearing frequency than wild‐type mice under equivalent loading conditions. Furthermore, injured ACL with silenced periostin expression, achieved through nanoparticle‐siRNA complex delivery, displayed an elevated propensity for apoptosis and senescence compared to intact ACL in C57BL/6 mice. Together, our findings underscore the pivotal role of periostin in ACL health, injury, and potential for healing. [ABSTRACT FROM AUTHOR]

During tumor expansion, breast cancer (BC) cells often experience reactive oxygen species accumulation and mitochondrial damage because of glucose shortage. However, the mechanism by which BC cells deal with the glucose-shortage-induced oxidative stress remains unclear. Here, we showed that MANF (mesencephalic astrocyte derived neurotrophic factor)-mediated mitophagy facilitates BC cell survival under glucose-starvation conditions. MANF-mediated mitophagy also promotes fatty acid oxidation in glucose-starved BC cells. Moreover, during glucose starvation, SENP1-mediated de-SUMOylation of MANF increases cytoplasmic MANF expression through the inhibition of MANF’s nuclear translocation and hence renders mitochondrial distribution of MANF. MANF mediates mitophagy by binding to PRKN (parkin RBR E3 ubiquitin protein ligase), a key mitophagy regulator, in the mitochondria. Under conditions of glucose starvation, protein oxidation inhibits PRKN activity; nevertheless, the CXXC motif of MANF alleviates protein oxidation in RING II-domain of PRKN and restores its E3 ligase activity. Furthermore, MANF-PRKN interactions are essential for BC tumor growth and metastasis. High MANF expression predicts poor outcomes in patients with BC. Our results highlight the prosurvival role of MANF-mediated mitophagy in BC cells during glucose starvation, suggesting MANF as a potential therapeutic target.Abbreviation: 2DG, 2-deoxy-D-glucose; 5TG, 5-thio-D-glucose; ACSL4/FACL4, acyl-CoA synthetase long chain family member 4; Baf A1, bafilomycin A1; BRCA, breast cancer; CHX, cycloheximide; DMF, distant metastasis-free; DMFS, distant metastasis-free survival; ECM, extracellular matrix; ER, endoplasmic reticulum; ERS, endoplasmic reticulum stress; F-1,6-BP, fructose-1,6-bisphosphate; FAO, fatty acid oxidation; GSH, reduced glutathione; GSVA, gene set variation analysis; HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; IF, immunofluorescence; MANF, mesencephalic astrocyte derived neurotrophic factor; Mdivi-1, mitochondrial division inhibitor 1; MFI, mean fluorescence intensity; NAC, N-acetyl-L-cysteine; OCR, oxygen-consumption rate; OS, overall survival; PMI, SQSTM1/p62-mediated mitophagy inducer; PPP, pentose phosphate pathway; PRKN, parkin RBR E3 ubiquitin protein ligase; RBR, RING in between RING; RFS, relapse-free survival; ROS, reactive oxygen species; SAPLIPs, saposin-like proteins; TCGA, The Cancer Genome Atlas; TNBC, triple-negative breast cancer; WT, wild type. [ABSTRACT FROM AUTHOR]

ABSTRACT A series of bis(thiosemicarbazide)gallium (III) complexes were synthesized and characterized by infrared spectroscopy, mass spectrometry, nuclear magnetic resonance, single‐crystal x‐ray crystallography, and density functional theory (DFT) calculation. The cytotoxicity of these gallium(III) complexes (CP 1–4) was subsequently evaluated against HCT‐116, HeLa, MDA‐MB‐231, and A549 cancer cell lines, as well as the normal cell line LO2, by MTT assays. The results indicated that CP‐1 displayed potent inhibitory effects against human colorectal cancer cells (HCT‐116) (IC50 = 0.03 ± 0.01) and human breast cancer cells (MDA‐MB‐231) (IC50 = 0.02 ± 0.01), significantly outperforming cisplatin. Moreover, CP‐2 exhibited notable selectivity towards MDA‐MB‐231 cells (IC50 = 5.01 ± 0.40) with minimal toxicity towards normal cells. Mechanistic studies revealed that treatment with CP 1–2 led to elevated intracellular reactive oxygen species (ROS) levels, resulting in cell cycle arrest at different phases. Specifically, CP‐1 induced G2/M phase arrest, inhibiting cancer cell proliferation, whereas CP‐2 hindered DNA synthesis (S phase) to impede cell proliferation. Furthermore, both CP‐1 and CP‐2 caused a reduction in mitochondrial membrane potential, activating the mitochondrial apoptotic pathway and inducing apoptosis in cancer cells. Molecular docking experiments demonstrated strong interactions between CP 1–2 and protein disulfide isomerase (PDI) at the molecular level. These findings suggest that CP‐1 and CP‐2 serve as potential anticancer agents, particularly showing promising potential in the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Bone marrow stromal cells (BMSCs) play a significant role in bone metabolism as they can differentiate into osteoblasts, bone marrow adipocytes (BMAds), and chondrocytes. BMSCs chronically exposed to nutrient overload undergo adipogenic programming, resulting in bone marrow adipose tissue (BMAT) formation. BMAT is a fat depot transcriptionally, metabolically, and morphologically distinct from peripheral adipose depots. Reactive oxygen species (ROS) are elevated in obesity and serve as important signals directing BMSC fate. ROS produced by the NADPH oxidase (NOX) family of enzymes, such as NOX4, may be responsible for driving BMSC adipogenesis at the expense of osteogenic differentiation. The dual nature of ROS as both cellular signaling mediators and contributors to oxidative stress complicates their effects on bone metabolism. This review discusses the complex interplay between ROS and BMSC differentiation in the context of metabolic bone diseases.Special attention is paid to the role of NOX4-ROS in regulating cellular processes within the bone marrow microenvironment and potential target in metabolic bone diseases. [ABSTRACT FROM AUTHOR]

Long-chain free fatty acids (FFAs) accumulation and oxidative toxicity is a major cause for several pathological conditions. The mechanisms underlying FFA cytotoxicity remain elusive. Here we show that palmitic acid (PA), the most abundant FFA in the circulation, induces S403 phosphorylation of SQSTM1/p62 (sequestosome 1) and its aggregation, which sequesters KEAP1 and activates the non-canonical SQSTM1-KEAP1-NFE2L2 antioxidant pathway. The PA-induced SQSTM1 S403 phosphorylation and aggregation are dependent on SQSTM1 K7-D69 hydrogen bond formation and dimerization in the Phox and Bem1 (PB1) domain, which facilitates the recruitment of TBK1 that phosphorylates SQSTM1 S403. The ubiquitin E3 ligase TRIM21 ubiquitinates SQSTM1 at the K7 residue and abolishes the PB1 dimerization, S403 phosphorylation, and SQSTM1 aggregation. TRIM21 is oxidized at C92, C111, and C114 to form disulfide bonds that lead to its oligomerization and decreased E3 activity. Mutagenizing the three C residues to S (3CS) abolishes TRIM21 oligomerization and increases its E3 activity. TRIM21 ablation leads to decreased SQSTM1 K7 ubiquitination, hence elevated SQSTM1 S403 phosphorylation and aggregation, which confers protection against PA-induced oxidative stress and cytotoxicity. Therefore, TRIM21 is a negative regulator of SQSTM1 phosphorylation, aggregation, and the antioxidant sequestration function. TRIM21 is oxidized to reduce its E3 activity that helps enhance the SQSTM1-KEAP1-NFE2L2 antioxidant pathway. Inhibition of TRIM21 May be a viable strategy to protect tissues from lipotoxicity resulting from long-chain FFAs.Abbreviations: ER: endoplasmic reticulum; FFA: free fatty acid; HMOX1/HO-1: heme oxygenase 1; IB: immunoblotting; IF: immunofluorescence; IP: immunoprecipitation; KEAP1: kelch like ECH associated protein 1; MASH: metabolic dysfunction-associated steatohepatitis; MEF: mouse embryonic fibroblast; NFE2L2/Nrf2: NFE2 like BZIP transcription factor 2; PA: palmitic acid; PB1: Phox and Bem 1; ROS: reactive oxygen species; SLD: steatotic liver disease; SQSTM1: sequestosome 1; TBK1: TANK-binding kinase 1; TRIM21: tripartite motif containing 21. [ABSTRACT FROM AUTHOR]

Background: Feline Herpesvirus type-1 (FHV-1) is a worldwide spread pathogen responsible for viral rhinotracheitis and conjunctivitis in cats that, in the most severe cases, can lead to death. Despite the availability of a variety of antiviral medications to treat this illness, mainly characterized by virostatic drugs that alter DNA replication, their use is often debated. Phytotherapeutic treatments are a little-explored field for FHV-1 infections and reactivations. In this scenario, natural compounds could provide several advantages, such as reduced side effects, less resistance and low toxicity. The purpose of this study was to explore the potential inhibitory effects of the green tea extract (GTE), consisting of 50% of polyphenols, on FHV-1 infection and reactive oxygen species (ROS) production. Results: Crandell-Reese feline kidney (CRFK) cells were treated with different doses of GTE (10–400 µg/mL) during the viral adsorption and throughout the following 24 h. The MTT and TCID50 assays were performed to determine the cytotoxicity and the EC50 of the extract, determining the amounts of GTE used for the subsequent investigations. The western blot assay showed a drastic reduction in the expression of viral glycoproteins (i.e., gB and gI) after GTE treatment. GTE induced not only a suppression in viral proliferation but also in the phosphorylation of Akt protein, generally involved in viral entry. Moreover, the increase in cell proliferation observed in infected cells upon GTE addition was supported by enhanced expression of Bcl-2 and Bcl-xL anti-apoptotic proteins. Finally, GTE antioxidant activity was evaluated by dichloro-dihydro-fluorescein diacetate (DCFH-DA) and total antioxidant capacity (TAC) assays. The ROS burst observed during FHV-1 infection was mitigated after GTE treatment, leading to a reduction in the oxidative imbalance. Conclusions: Although further clinical trials are necessary, this study demonstrated that the GTE could potentially serve as natural inhibitor of FHV-1 proliferation, by reducing viral entry. Moreover, it is plausible that the extract could inhibit apoptosis by modulating the intrinsic pathway, thus affecting ROS production. [ABSTRACT FROM AUTHOR]

Higher levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT), a TLR4 agonist, are associated with poor clinical outcomes in sepsis-induced acute lung injury (ALI). Little is known regarding the mechanisms by which eNAMPT is involved in ALI. Our recent work has identified a crucial role for mitochondrial dysfunction in ALI. Thus, this study aimed to determine if eNAMPT-mediated inflammatory injury is associated with the loss of mitochondrial function. Our data show that eNAMPT disrupted mitochondrial bioenergetics. This was associated with cytoskeleton remodeling and the loss of endothelial barrier integrity. These changes were associated with enhanced mitochondrial fission and blocked when Rho-kinase (ROCK) was inhibited. The increases in mitochondrial fission were also associated with the nitration-mediated activation of the small GTPase activator of ROCK, RhoA. Blocking RhoA nitration decreased eNAMPT-mediated mitochondrial fission and endothelial barrier dysfunction. The increase in fission was linked to a RhoA-ROCK mediated increase in Drp1 (dynamin-related protein 1) at serine(S)616. Another TLR4 agonist, lipopolysaccharide (LPS), also increased mitochondrial fission in a Drp1 and RhoA-ROCK-dependent manner. To validate our findings in vivo , we challenged C57BL/6 mice with eNAMPT in the presence and absence of the Drp1 inhibitor, Mdivi-1. Mdivi-1 treatment protected against eNAMPT-induced lung inflammation, edema, and lung injury. These studies demonstrate that mitochondrial fission-dependent disruption of mitochondrial function is essential in TLR4-mediated inflammatory lung injury and identify a key role for RhoA-ROCK signaling. Reducing mitochondrial fission could be a potential therapeutic strategy to improve ARDS outcomes. [Display omitted] • eNAMPT disrupts endothelial barrier integrity and mitochondrial function in pulmonary endothelial cells. • Mitochondrial fission induced by eNAMPT depends on actin cytoskeleton remodeling via Rho-kinase (ROCK). • eNAMPT increases superoxide generation, subsequently activating the small GTPase activator of ROCK (RhoA) via nitration. • Activation of RhoA contributes to the effects of eNAMPT on mitochondrial network dynamics through the activation of Drp1. • Drp1 inhibition is protective against eNAMPT-induced inflammatory lung injury in mice. [ABSTRACT FROM AUTHOR]

Viruses, bacteria, fungus, protozoans, and different metazoan parasites and parasitoids present a constant threat to insects. Insect immunity has two components: humoral and cell mediated. Humoral immunity can be achieved by various antimicrobial proteins, namely, cecropins, sarcotoxin, defensin, attacin, etc. The cell‐mediated immunity comprises various cells having immune functions fostering nodulation, phagocytosis, microaggregation, encapsulation etc. Eicosanoids play a crucial role in insect immunity comparable to other animals. The above‐mentioned are signaling molecules derived from polyunsaturated fatty acids and they exert numerous physiological effects, namely, inflammation, immune modulation, and regulation of cellular processes. The review article elucidates various roles of eicosanoids, namely, nodulation reaction, Toll signaling pathway, nitric oxide (NO) generation, Ca2+ mobilization, production of reactive oxygen species (ROS), actin polymerization and aquaporin activation. Eicosanoids can function in immune priming in insects drawing hemocytes. An agent named Duox was also identified serving as ROS generator in insect gut. Moreover, role of Repat gene in insect immunity was also studied. However, recently the role of prostacyclin (PGI2) was found to be negative as it inhibits platelet aggregation. In this brief review, we have tried to shed light on the various functions of eicosanoids in immunity of insect those have been discovered recently. This concise study will allow to decipher eicosanoids’ function in insect immunity in a nutshell, and it will pave the way for more researches to understand the key players of insect immunity which may eventually help to develop novel vector and pest control strategies in near future. [ABSTRACT FROM AUTHOR]

Dysregulation of splicing factor expression plays a crucial role in the progression of hepatocellular carcinoma (HCC). Our research found that the expression level of splicing factor ZMAT2 was increased in HCC, promoting the proliferation of HCC cells. RNAseq data indicated that the absence of ZMAT2 induced skipping exon of mRNA, while RIPseq data further revealed the mRNA binding motifs of ZMAT2. A comprehensive analysis of RNAseq and RIPseq data indicateed that ZMAT2 played a crucial role in the maturation process of TRIM28 mRNA. Knocking down of ZMAT2 led to the deletion of 25 bases in exon 11 of TRIM28, ultimately resulting in nonsense-mediated decay (NMD). Our data revealed that ZMAT2 could regulate TRIM28 to reduce the accumulation of ROS in HCC cells, thereby promoting their proliferation. Our research also discovered that ZMAT2 was capable of undergoing phase separation, resulting in the formation of liquid droplet condensates within HCC cells. Additionally, it was found that ZMAT2 was able to form protein-nucleic acid condensates with TRIM28 mRNA. In summary, this study is the first to reveal that ZMAT2 and TRIM28 mRNA form protein-nucleic acid condensates, thereby regulating the splicing of TRIM28 mRNA. The increased expression of ZMAT2 in HCC leads to upregulated TRIM28 expression and reduced ROS accumulation, ultimately accelerating the proliferation of HCC cells. [ABSTRACT FROM AUTHOR]

Chronic vascular encephalopathy (CVE) is a frequent cause of vascular mild cognitive impairment and dementia, which significantly worsens the quality of life, especially in the elderly population. CVE is a result of chronic cerebral hypoperfusion, characterized by prolonged limited blood flow to the brain. This causes insufficient oxygenation of the brain leading to hypoxia. The latter can trigger a series of events associated with the development of oxidative/reductive stresses and neuroinflammation. Addressing the gap in knowledge regarding oxidative and reductive stresses in the development of vascular disorders and neuroinflammation can give a start to new directions of research in the context of CVE. In this review, we consider the hypoxiainduced molecular challenges involved in the pathophysiology of CVE, focusing on oxidative stress and neuroinflammation, which are combined in a vicious cycle of neurodegeneration. We also briefly describe therapeutic approaches to the treatment of CVE and outline the prospects for the use of sulforaphane, an isothiocyanate common in cruciferous plants, and vitamin D to break the vicious cycle and alleviate the cognitive impairments characteristic of patients with CVE. [ABSTRACT FROM AUTHOR]

Background: Increased prevalence of hepatocellular carcinoma (HCC) remains a global health challenge. HCC chemoresistance is a clinical obstacle for its management. Aberrant miRNA expression is a hallmark for both cancer progression and drug resistance. However, it is unclear which miRNAs are involved in HCC chemoresistance. Methods: MicroRNA microarray analysis revealed a differential expression profile of microRNAs between the hepatocellular carcinoma HA22T cell line and the HDACi-R cell line, which was validated by quantitative real-time PCR (qRT-PCR). To determine the biological function of miR-342-5p and the mechanism of the microRNA-342-5p/CFL1 axis in hepatocellular carcinoma HDACi resistance, loss- and gain-of-function studies were conducted in vitro. Results: Here we demonstrated the molecular mechanism of histone deacetylase inhibitor (HDACi) resistance in HCC. Differential miRNA expression analysis showed significant down regulation of miR-342-5p in HDACi-R cells than in parental HA22T cells. Mimics of miR-342-5p enhanced apoptosis through upregulation of Bax, cyto-C, cleaved-caspase-3 expressions with concomitant decline in anti-apoptotic protein (Bcl-2) in HDACi-R cells. Although HDACi did not increase cell viability of HDACi-R, overexpression of miR-342-5p decreased cofilin-1 expression, upregulated reactive oxygen species (ROS) mediated apoptosis, and sensitized HDACi-R to HDACi in a dose-dependent manner. Conclusion: Our findings demonstrated the critical role of miR-342-5p in HDACi resistance of HCC and that this mechanism might be attributed to miR-342-5p/cofilin-1 regulation. [ABSTRACT FROM AUTHOR]

Methylglyoxal (MGO) triggers oxidative stress responses in vascular endothelial cells, leading to apoptosis linked to diabetic vascular complications. Total flavonoids of Eucommia ulmoides leaves (TFEL) display antioxidant activity, yet its prevention of MGO‐induced apoptosis and mechanisms are unclear. Our study used western blotting and ELISA to evaluate protein levels and enzyme activities. Cell viability and apoptosis were evaluated using CCK8 assay and PE Annexin V/7‐AAD double staining. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured using fluorescence probes. Vascular pathological changes and apoptosis were analyzed through H&E and TUNEL staining. In vitro, MGO‐stimulated human umbilical vein endothelial cells (HUVECs) were treated with varying TFEL concentrations. Our results demonstrated that TFEL significantly enhanced cell viability, reduced apoptosis, downregulated caspase‐3 activity, and Bax/Bcl‐2 ratio. Moreover, TFEL markedly suppressed MGO‐induced ROS and malondialdehyde (MDA) production while restoring antioxidant enzyme activity and MMP. TFEL pretreatment promoted the expression of p‐Akt, Nrf2, and HO‐1 proteins. Pharmacological inhibition of p‐Akt significantly suppressed the upregulation of Nrf2 and HO‐1 protein levels mediated by TFEL. Consistently, pharmacological inhibition of Nrf2 or p‐Akt partially abrogated the protective effects of TFEL against MGO‐induced damage in HUVECs. In vivo studies revealed that TFEL (100 and 200 mg/kg) partially restored antioxidant capacity and reduced aortic thickness and apoptosis in MGO‐injured mice. In conclusion, the findings indicate that TFEL mitigates MGO‐induced apoptosis via activation of p‐Akt/Nrf2/HO‐1 and scavenging of oxidative stress, highlighting its potential in diabetic vascular complication management. [ABSTRACT FROM AUTHOR]

AbstractPetrol vapors as important occupational and environmental pollutants can cause oxidative stress and may play a role in the development of neurodegenerative diseases along with the risk factors involved. This research is designed as a preliminary study to evaluate the protective effects of apigenin (APG) on oxidative stress caused by petrol vapors inhalation in rats. A total of 24 male Wistar rats were randomly divided into four groups inside the inhalation chamber. Body weight changes and oxidative stress markers were investigated. The average body weight of the group exposed to petrol vapors was significantly lower compared to the other groups. The level of reactive oxygen species (ROS), content of oxidized-glutathione (GSSG), and Malondialdehyde were found to be higher in the petrol-inhaled group, while the content of reduced-glutathione (GSH) was lower compared to the other groups. APG administration did result in any significant improvement in these toxicities induced by petrol vapor. APG administration may ameliorate the petrol-induced oxidative stress. In chronic exposures, in addition to personal protection and engineering control, the use of compounds of natural origin may help in reducing the side effects (such as CNS) caused by exposure to petrol vapors. [ABSTRACT FROM AUTHOR]

Background: PaBing-II Formula (PB-II) is a traditional Chinese medicine for treating Parkinson's disease (PD). However, owing to the complexity of PB-II and the difficulty in obtaining human dopaminergic neurons (DAn), the mechanism of action of PB-II in PD treatment remains unclear. The aim of this study was to investigate the mechanisms underlying the therapeutic benefits of PB-II in patients with PD. Methods: hiPSCs derived DAn were treated with H2O2 to construct the DAn oxidative damage model. SwissTargetPrediction was employed to predict the potential targets of the main compounds in serum after PB-II treatment. Metascape was used to analyze the pathways. Sprague-Dawley rats were used to construct the 6-hydroxydopamine (6-OHDA)-induced PD model, and the duration of administration was four weeks. RNA sequencing was used for Transcriptome analysis to find the signal pathways related to neuronal damage. The associated inflammatory factors were detected by enzyme-linked immunosorbent assay (ELISA). We identified PB-II as an Nrf2 activator using antioxidant-responsive element luciferase assay in MDA-MB-231 cells. Results: In vitro experiments showed that the treatment of PB-II-treated serum increased the percentage of TH+ cells, decreased inflammation and the apoptosis, reduced cellular reactive oxygen species, and upregulated the expression of Nrf2 and its downstream genes. Pathway analysis of the RNAseq data of samples before and after the treatment with PB-II-treated serum identified neuron-associated pathways. In vivo experiments demonstrated that PB-II treatment of PD rat model could activate the Nrf2 signaling pathway, protect the midbrain DAn, and improve the symptoms in PD rats. Conclusion: PB-II significantly protects DAn from inflammation and oxidative stress via Nrf2 pathway activation. These findings elucidate the roles of PB-II in PD treatment and demonstrate the application of hiPSC-derived DAn in research of Chinese medicine. [ABSTRACT FROM AUTHOR]