Excessive Accumulation Research Articles

CLINICAL STUDY OF BODY MASS INDEX ON WOUND INFECTION AND HEALING EFFECTS

Background: Obesity, characterized by excess fat accumulation, is associated with heightened inflammation and infection risk. However, the relationship between body mass index (BMI) and wound healing remains unclear. Objective: The study aimed to explore the relationship between BMI and wound infection incidence, pathogenic bacterial strains in wounds, and wound healing promotion using different BMI values in conventional medical dressings. Methods: The study included 120 patients with traumatic and orthopedic wound infections and 40 patients with vertebral fractures to assess dressing efficacy and the influence of BMI index on healing outcomes. Wound infection incidence rates, pathogenic bacteria distribution within groups, and antibiotic resistance were identified, and their association with BMI was evaluated. Factors contributing to wound infection were analyzed. Results: The wound infection incidence rate was 30.36% without statistically significant correlation with BMI ([Formula: see text]). A weak correlation ([Formula: see text]) was established between the distribution of pathogenic bacterial strains with cause of trauma and BMI ([Formula: see text]). Wound exposure time ([Formula: see text]), wound depth ([Formula: see text]), and hospital stay ([Formula: see text]) were identified as independent wound infection risk factors. Conclusions: BMI exhibited a weak correlation with pathogenic bacteria distribution and negatively correlated with the degree of wound healing.

Withaferin A Ameliorated the Bone Marrow Fat Content in Obese Male Mice by Favoring Osteogenesis in Bone Marrow Mesenchymal Stem Cells and Preserving the Bone Mineral Density.

Obesity and osteoporosis are two prevalent conditions that are becoming increasingly common worldwide, primarily due to aging populations, imbalanced energy intake, and sedentary lifestyles. Obesity, characterized by excessive fat accumulation, and osteoporosis, marked by reduced bone density and increased fracture risk, are often interconnected. High-fat diets (HFDs) can exacerbate both conditions by promoting bone marrow adiposity and bone loss. The effect of WFA on the osteogenesis and adipogenesis was studied on the C3H10T1/2 cell line and bone marrow mesenchymal stem cells (BM-MSCs) isolated from mice. We used oil red O and alkaline phosphatase (ALP) staining to observe adipogenesis and osteogenesis, respectively, in MSCs. Real-time PCR and Western blot analyses were used to study the molecular effects of WFA on MSCs. We employed micro-CT to analyze the bone microarchitecture, bone mineral density (BMD), and abdominal fat mass in male mice. We have used osmium tetroxide (OsO4) staining to study the bone marrow fat. WFA induced the C3H10T1/2 cell line and BM-MSCs toward osteogenic lineage as evidenced by the higher ALP activity. WFA also downregulated the lipid droplet formation and adipocyte specific genes in MSCs. In the in vivo study, WFA also suppressed the bone catabolic effects of the HFD and maintained the bone microarchitecture and BMD in WFA-treated animals. The bone marrow adipose tissue was reduced in the tibia of WFA-treated groups in comparison with only HFD-fed animals. Withaferin A was able to improve the bone microarchitecture and BMD by committing BM-MSCs toward osteogenic differentiation and reducing marrow adiposity. The findings of this study could provide valuable insights into the therapeutic potential of Withaferin A for combating bone marrow obesity and osteoporosis, particularly in the context of diet-induced metabolic disturbances.

Characteristics of the hemostatic system “P-selectin — von Willebrand factor — metalloprotease ADAMTS13” during childbirth

Introduction. The physiological task of the blood coagulation system during childbirth is to prevent excessive blood loss.Aim: to evaluate the quantitative and qualitative characteristics in the system P-selectin-von Willebrand factor (vWF)-metallo-protease ADAMTS13 during natural and uncomplicated childbirth in women with a physiological pregnancy.Materials and methods. The study included 40 pregnant women without somatic pathology, with a physiologically progressing pregnancy that ended with physiological birth (general group). Of these, 16 women had their first birth (group 1), 18 had their second birth (group 2) and 6 had their third birth (group 3). Venous blood sampling was performed at three points throughout the study: 1st point — the onset of labor, 2nd point — 2 hours after childbirth and 3rd point — 24 hours after child -birth. The control group consisted of 25 healthy non-pregnant women. The blood samples were examined for: vWF antigen (vWF:Ag), binding ability of vWF to platelet receptor GPIb (vWF:GPIb), binding ability of vWF to collagen type I (vWF:CBAI) and type III (vWF:CBAIII), antigen and activity ADAMTS13 (ADAMTS13:Ag and ADAMTS13:AC), antibodies to ADAMTS13 (ADAMTS13:AB) and P-selectin.Results. The medians of the studied vWF characteristics in the genera l group were statistically significantly higher compared to the control group at all study points, with the exception of the medians of the vWF:GPIb/vWF:Ag ratio, which in the general group were statistically significantly lower at all study points when compared with the control group. The median values of vWF:GPIb and vWF:Ag in women in the second group were statistically significantly higher at all points of the study, compared with similar indicators in both the first and third groups. The median values of ADAMTS13:AC and ADAMTS13:AB in the overall group were statistically significantly higher when compared with the control group at all study points. Median ADAMTS13:Ag and ADAMTS13:AC/ADAMTS13:Ag ratios were statistically significantly lower at all study points. Individual P-selectin values varied widely from 212.1 to 1398 ng/ml, but the medians of this indicator were statistically significantly higher in all study groups and at all study points compared to the control group.Conclusion. The increase in platelet-binding and collagen-binding abilities of vWF suggests that these adhesive properties of the hemostatic protein play an important role in preventing excessive bleeding during labor. Taking into account the decrease in the vWF:GPIb/vWF:Ag ratio compared to the control group, the adhesion of vWF to collagen is more important under these conditions. Despite the fact that ADAMTS13 concentration does not decrease, an actual twofold increase in its activity provides a sufficient antithrombotic effect. The interaction between vWF and ADAMTS13 under conditions of physiological labor does not lead to excessive formation and accumulation of high-affinity antibodies to ADAMTS13.

Pilocarpine mediated excessive calcium accumulation leads to ciliary muscle cell senescence and apoptosis.

The ciliary muscle constitutes a crucial element in refractive regulation. Investigating the pathophysiological mechanisms within the ciliary muscle during excessive contraction holds significance in treating ciliary muscle dysfunction. A guinea pig model of excessive contraction of the ciliary muscle induced by drops pilocarpine was employed, alongside the primary ciliary muscle cells was employed in invitro experiments. The results of the ophthalmic examination showed that pilocarpine did not significantly change refraction and axial length during the experiment, but had adverse effects on the regulatory power of the ciliary muscle. The current data reveal notable alterations in the expression profiles of hypoxia inducible factor 1 (HIF-1α), ATP2A2, P53, α-SMA, Caspase-3, and BAX within the ciliary muscle of animals subjected to pilocarpine exposure, alongside corresponding changes observed in cultured cells treated with pilocarpine. Augmented levels of ROS were detected in both tissue specimens and cells, culminating in a significant increase in cell apoptosis in invivo and invitro experiments. Further examination revealed that pilocarpine induced an increase in intracellular Ca2+ levels and disrupted MMP, as evidenced by mitochondrial swelling and diminished cristae density compared to control conditions, concomitant with a noteworthy decline in antioxidant enzyme activity. However, subsequent blockade of Ca2+ channels in cells resulted in downregulation of HIF-1α, ATP2A2, P53, α-SMA, Caspase-3, and BAX expression, alongside ameliorated mitochondrial function and morphology. The inhibition of Ca2+ channels presents a viable approach to mitigate ciliary cells damage and sustain proper ciliary muscle function by curtailing the mitochondrial damage induced by excessive contractions.

Involvement of lysophosphatidic acid-LPA1-YAP signaling in healthy and pathological FAPs migration

Skeletal muscle fibrosis is defined as the excessive accumulation of extracellular matrix (ECM) components and is a hallmark of muscular dystrophies. Fibro-adipogenic progenitors (FAPs) are the main source of ECM, and thus have been strongly implicated in fibrogenesis. In skeletal muscle fibrotic models, including muscular dystrophies, FAPs undergo dysregulations in terms of proliferation, differentiation, and apoptosis, however few studies have explored the impact of FAPs migration.Here, we studied fibroblast and FAPs migration and identified lysophosphatidic acid (LPA), a signaling lipid central to skeletal muscle fibrogenesis, as a significant migration inductor. We identified LPA receptor 1 (LPA1) mediated signaling as crucial for this effect through a mechanism dependent on the Hippo pathway, another pathway implicated in fibrosis across diverse tissues. This cross-talk favors the activation of the Yes-associated protein 1 (YAP) and Transcriptional coactivator with PDZ-binding motif (TAZ), leading to increased expression of fibrosis-associated genes. This study reveals the role of YAP in LPA-mediated fibrotic responses as inhibition of YAP transcriptional coactivator activity hinders LPA-induced migration in fibroblasts and FAPs.Moreover, we found that FAPs derived from the mdx4cv mice, a murine model of Duchenne muscular dystrophy, display a heightened migratory phenotype due to enhanced LPA signaling compared to wild-type FAPs. Remarkably, we found that the inhibition of LPA1 or YAP transcriptional coactivator activity in mdx4cv FAPs reverts this phenotype. In summary, the identified LPA-LPA1-YAP pathway emerges as a critical driver of skeletal muscle FAPs migration and provides insights into potential novel targets to mitigate fibrosis in muscular dystrophies.

SiTGF-β1 and pirfenidone contained Ionizable-Liposomal nanodrug for enhanced treatment of Idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a challenging interstitial lung disease characterized by heterogeneous manifestations and significant mortality. Due to the relative complexity of IPF pathogenesis, currently approved clinical drugs mainly for anti-inflammatory or anti-fibrotic present limited disease containment and insufficient damage repair, falling far short of previous expectations. To address this limitation, we developed an ionizable liposome nanodrug (named as TPNPs) co-loaded with small interfering RNA targeting TGF-β1 (siTGF-β1) and pirfenidone (PFD) for enhanced IPF therapy. The siTGF-β1 (blocking TGF-β signaling pathway) and PFD were carefully selected and integrated in consideration of their crucial roles in endothelial mesenchymal transition, alveolar epithelial cell apoptosis, and fibroblast differentiation and migration, which are closely related to IPF development. As a result, TPNPs exhibited synergistic enhancement effects against the damage of alveolar epithelial cells and fibroblasts in vitro. Notably, repeated administration of TPNPs mitigated the injury to alveolar epithelium, inhibited the excessive accumulation of extracellular matrix (ECM), and alleviated the destruction of lung, thereby synergistically ameliorating the lung function in a bleomycin (BLM)-induced murine model. This work provides a promising therapeutic strategy that combines nucleic acid with small molecule for enhanced treatment of IPF.

Accumulation of Heavy Metals in Blueberry (Vaccinium myrtillus L.) and Dominant Mosses (Pleurozium schreberi (Willd. ex Brid.) Mitt.) as Bioindicators of the Expressway Influence on Forest Ecosystems

The intensive use, development, and expansion of the road network is expanding the zones of direct impact of road transport on forest ecosystems. Issues related to the mobility of trace elements in forest ecosystems along motorways are very important due to the numerous environmental risks associated with the excessive accumulation of metals, the ability to migrate and accumulate in plants and animals, and the risk of transferring these elements to higher trophic levels. The aim of this article was therefore to determine the impact of road traffic on the basis of contents of trace metals Cd, Cr, Cu, Ni, Pb, and Zn and to describe the relationship of these contents in moss gametophytes and blueberry leaves taken in the vicinity of an existing and variously expanded expressway (S7, Poland, Europe). Analyses of transport impacts included the effects of distance and time of pollutant deposition and road transport on habitat and stand conditions. The highest contents of Cd, Cr, Cu, Ni, Pb, and Zn in moss tissues were found in fir stands and the contents were, respectively, 0.36 mg·kg−1, 5.91 mg·kg−1, 12.5 mg·kg−1, 3.26 mg·kg−1, 8.82 mg·kg−1, and 55.28 mg·kg−1. Mosses showed the best bioindication capacity of all of the studied ecosystem elements. The Pb, Zn, Cr, Cu, and Ni contents were particularly markedly elevated in moss tissues relative to non-anthropopressured areas and dependent on distance from the emitter (road). Blueberry proved to be a less useful bioindicator, as the contents of Cd, Cr, Cu, Ni, Pb, and Zn found were similar to the data from non-anthropopressured areas and were, respectively, 0.09 mg·kg−1, 0.98 mg·kg−1, 7.12 mg·kg−1, 2.49 mg·kg−1, 1.18 mg·kg−1, and 15.91 mg·kg−1 in fir stands and 0.04 mg·kg−1, 0.47 mg·kg−1, 6.63 mg·kg−1, 1.65 mg·kg−1, 0.72 mg·kg−1, and 17.44 mg·kg−1 in pine stands.

Chronic ethanol exposure induces cardiac fibroblast transdifferentiation via ceramide accumulation and oxidative stress

Aims Excessive alcohol consumption is associated with cardiac dysfunction and the development of myocardial fibrosis. In this study, we aimed to investigate the direct impacts of ethanol on myocardial fibroblasts and elucidate the underlying mechanism responsible for chronic ethanol-induced myocardial fibrosis. Methods Rat primary cardiac fibroblasts exposed to ethanol for 24 h and C57BL/6J mice fed on Lieber–DeCarli diet to establish an ethanol intoxication model in vitro and in vivo, respectively. Histological analyses, molecular biology techniques, and analytical chemistry methods were then conducted. Results and conclusion In vivo and vitro experiments revealed that chronic ethanol exposure induced increased myocardial fibrosis and augmented the transdifferentiation of myocardial fibroblasts. Simultaneously, it elicited an upregulation in the production of long-chain and very-long-chain ceramides in cardiac fibroblasts. The excessive accumulation of ceramide leads to elevated levels of intracellular oxidative stress, culminating in the activation of TGF-β-SMAD3 signaling and the development of fibrosis. Intervention of these pathways with pharmacological inhibitors in vitro or in vivo inhibited fibrosis. In conclusion, ethanol increased ceramides and reactive oxygen species (ROS) in cardiac fibroblasts, resulting in the activation of TGF-β-SMAD3 signaling, transdifferentiation of fibroblasts, and myocardial fibrosis.

Imbalance of early-life vitamin D intake targets ROS-mediated crosstalk between mitochondrial dysfunction and differentiation potential of MSCs associated the later obesity

BackgroundObesity is characterized by excessive fat accumulation, which is related with abnormal pluripotency of mesenchymal stem cells (MSCs). Recently, there is growing evidence that the disorder of maternal vitamin D (VD) intake is a well-known risk factor for long-term adverse health outcomes to their offspring. Otherwise, less is known of its repercussion and underlying mechanisms on the different differentiation potential of MSCs.MethodsFour-week-old female C57BL/6J mice were fed with different VD reproductive diets throughout the whole pregnancy and lactation. The characteristics of BMSCs from their seven-day male offspring, VDR knockdown establishment of HuMSCs and HuMSCs under the different VD interventions in vitro were confirmed by flow cytometry, RT-PCR, and immunofluorescence. The roles of VD on their mitochondrial dysfunction and differentiation potential were also investigated. Then their remaining weaned male pups were induced by administrating high-fat-diet (HFD) for 16 weeks and normal fat diet was simultaneously as controls. Their lipid accumulation and adipocytes hypertrophy were determined by histological staining and related gene expressions.ResultsHerein, it was proved that imbalance of early-life VD intake could significantly aggravate the occurrence of obesity by inducing the adipogenesis through affecting the VD metabolism and related metabolites (P < 0.05). Moreover, abnormally maternal VD intake might be involved on the disorders of differentiation potential to inhibit the maintenance of MSCs stemness through increasing the productions of ROS, which was accompanied by impairing the expression of related genes on the adipo-osteogenic differentiation (P < 0.05). Moreover, it was along with increasing potential of adipogenic differentiation of MSCs as higher ROS in the state of VD deficiency, while excessive maternal VD status could conversely enhance the osteogenic differentiation with slightly lower ROS (P < 0.05). Furthermore, the underlying mechanisms might be involved on the mitochondria dysfunctional, especially the mitophagy, by activating the LC3b, P62 and etc. using in vivo and in vitro studies (P < 0.05).ConclusionThese findings demonstrated that imbalance of early-life VD intake could target ROS-mediated crosstalk between mitochondrial dysfunction and differentiation potential of MSCs, which was significantly associated with the later obesity. Obviously, our results could open up an attractive modality for the benefits of suitable VD intake during the pregnancy and lactation.

Influence of internal bypass conditions on the double bypass matching characteristics of variable cycle high-pressure compression system

The variable cycle high-pressure compression system (VCHCS) consists of a core driven fan stage (CDFS) and a high-pressure compressor (HPC), which are crucial components for controlling the variable cycle engine's bypass ratio. However, the double bypass (DB) matching mechanism of the VCHCS remains insufficiently understood. This study focuses on investigating the DB matching characteristics of the VCHCS under different representative internal bypass conditions. The findings demonstrate that as the internal bypass conditions transition from near choke to near stall, the external bypass stability margin of the VCHCS decreases progressively, and the external bypass characteristic curve of the HPC exhibits an approximate “counter-clockwise rotation” pattern. Furthermore, the operating state of the CDFS and the redistribution of internal and external bypass flow rate, collectively determine the matching state of the compressor system. Building upon the aforementioned summarization regarding the impact of internal bypass conditions on the matching characteristics of the VCHCS, this research integrates flow field analysis to explicate the mechanism of stall under typical operating conditions. The investigation reveals that, when the internal bypass condition under design point and the external bypass condition approaches the stall boundary, an excessive accumulation of low-energy fluid occurs at the external bypass outlet guide vane, subsequently triggers the occurrence of stall. Specifically, when the internal bypass conditions under the near stall point, the predominant limitation on further elevation or reduction of external bypass back pressure lies in the extensive blockage of a massive low-energy fluid on the suction surface of the HPC second stage stator.

Integrated transcriptomics- and structure-based drug repositioning identifies drugs with proteasome inhibitor properties

Computational pharmacogenomics can potentially identify new indications for already approved drugs and pinpoint compounds with similar mechanism-of-action. Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238). In vitro validation of candidate compounds was then performed to assess proteasomal proteolytic activity, accumulation of ubiquitinated proteins, cell viability, and drug-induced expression in A375 melanoma and MCF7 breast cancer cells. Using this approach, we identified six compounds with PI properties ((-)-kinetin-riboside, manumycin-A, puromycin dihydrochloride, resistomycin, tegaserod maleate, and thapsigargin). Although the docking scores pinpointed their ability to bind to the β5 subunit, our in vitro study revealed that these compounds inhibited the β1, β2, and β5 catalytic sites to some extent. As shown with bortezomib, only manumycin-A, puromycin dihydrochloride, and tegaserod maleate resulted in excessive accumulation of ubiquitinated proteins and elevated HMOX1 expression. Taken together, our integrated drug repositioning approach and subsequent in vitro validation studies identified six compounds demonstrating properties similar to proteasome inhibitors.

Bioinformatics Identification and Experimental Verification of Disulfidptosis-Related Genes in the Progression of Osteoarthritis.

Osteoarthritis (OA) is a disabling and highly prevalent condition affecting millions worldwide. Recently discovered, disulfidptosis represents a novel form of cell death induced by the excessive accumulation of cystine. Despite its significance, a systematic exploration of disulfidptosis-related genes (DRGs) in OA is lacking. This study utilized three OA-related datasets and DRGs. Differentially expressed (DE)-DRGs were derived by intersecting the differentially expressed genes (DEGs) from GSE114007 with DRGs. Feature genes underwent screening through three machine learning algorithms. High diagnostic value genes were identified using the receiver operating characteristic curve. Hub genes were confirmed through expression validation. These hub genes were then employed to construct a nomogram and conduct enrichment, immune, and correlation analyses. An additional validation of hub genes was performed through in vitro cell experiments. SLC3A2 and PDLIM1 were designated as hub genes, displaying excellent diagnostic performance. PDLIM1 exhibited low expression in early chondrocyte differentiation, rising significantly in the late stage, while SLC3A2 showed high overall expression, declining in the late differentiation stage. Cellular experiments corroborated the correlation of SLC3A2 and PDLIM1 with chondrocyte inflammation. Two hub genes, SLC3A2 and PDLIM1, were identified in relation to disulfidptosis, providing potential directions for diagnosing and treating OA.

Proatherogenic proteomic profile of LDL isolated from plasma of patients with diabetes mellitus: immunological aspects

Atherosclerosis is a vascular disease, which is based on a chronic inflammatory process, including complex interactions between blood components, as well as the cells that form the vessel wall, and lipid metabolism in general. Low-density lipoproteins (LDL) play a key role in pathogenesis of atherosclerosis. When the permeability of the endothelial layer of the vessel is impaired, LDL can penetrate into the intramural space and lead to excessive cholesterol accumulation by the cells from the intima subendothelial layer, leading to the onset of the inflammatory process and to the formation of foam cells, the main morphological component of the atherosclerotic plaque. However, the level of LDL in the patient’s blood plasma alone is not a key indicator of the development of atherosclerosis. Numerous studies point out the role of oxidized modifications of LDL (oxLDL) in the increased local accumulation of cholesterol in vascular wall cells, however, recent works have shown conflicting results regarding the role of oxLDL in the development of atherosclerosis. We hypothesize that other components of LDL may also influence the progression of atherosclerosis. It is a well-known fact that patients with diabetes mellitus (DM) suffer from cardiovascular diseases, in particular atherosclerosis, more often than patients without diagnosed DM and other autoimmune diseases, and the disease progresses faster. The purpose of this study was to identify risk biomarkers in LDL groups that indicate the relationship of the immune system with the development of atherosclerosis in such patients. LDL was isolated from patients and healthy donors using continuous ultracentrifugation with solutions of different densities, and LDL protein profile samples were measured using gas chromatography-mass spectrometry. We found 9 proteins that had a statistically significant difference between the samples (DM and control). In the diabetes group, the content of the antimicrobial peptide cathelicidin and lipopolysaccharide-binding protein was almost 2 times higher compared to the control. These proteins may be involved in the development of inflammation, leading to the progression of atherosclerosis. At the same time, a decrease in immunoglobulins and complement components (C9 and Complement C1s subcomponent) associated with LDL may contribute to the development of atherosclerosis.

Lipid accumulation product and type 2 diabetes risk: a population-based study

BackgroundThe Lipid Accumulation Product (LAP) is a measure that indicates excessive fat accumulation in the body. LAP has been the focus of research in epidemiological studies aimed at forecasting chronic and metabolic diseases. This study aimed to evaluate the association between LAP and type 2 diabetes mellitus (T2DM) among adults in western Iran.MethodsThe study involved 9,065 adults who participated in the initial phase of the Ravansar non-communicable diseases study (RaNCD) cohort. To investigate the association between LAP and T2DM, multiple logistic regressions were employed. Additionally, the receiver operating characteristic (ROC) curve was used to evaluate LAP’s predictive ability concerning T2DM.ResultsThe participants had an average age of 47.24 ± 8.27 years, comprising 49.30% men and 50.70% women. The mean LAP was 53.10 ± 36.60 for the healthy group and 75.51 ± 51.34 for the diabetic group (P < 0.001). The multiple regression analysis revealed that the odds of T2DM in the second quartile of LAP were 1.69 (95% CI: 1.25, 2.29) times greater than in the first quartile. Furthermore, the odds in the third and fourth quartiles were 2.67 (95% CI: 2.01, 3.55) and 3.73 (95% CI: 2.83, 4.92) times higher, respectively. The ROC analysis for predicting T2DM showed that the LAP index had an area under the curve (AUC) of 0.66 (95% CI: 0.64, 0.68).ConclusionA strong association was identified between elevated LAP levels and T2DM in the adult population of western Iran. LAP is recommended as a potential tool for screening diabetes susceptibility.

The influence of metabolic disorders on adaptive immunity.

The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis. Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired. There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired. In the context of metabolic disorders, chronic inflammation is suggested to be a major contributor to disease progression. A major contributor to tissue dysfunction in metabolic disease is ectopic lipid deposition, which is generally caused by diet and genetic factors. Thus, we propose the idea, that similar to tissue and organ damage in metabolic disorders, excessive accumulation of lipid in immune cells promotes a dysfunctional immune system (beyond the classical foam cell) and contributes to disease pathology. Herein, we review the evidence that lipid accumulation through diet can modulate the production and function of immune cells by altering cellular lipid content. This can impact immune cell signalling, activation, migration, and death, ultimately affecting key aspects of the immune system such as neutralising pathogens, antigen presentation, effector cell activation and resolving inflammation.

Phosphorous accumulation associated with mitochondrial PHT3-mediated enhanced arsenate tolerance in Chlamydomonas reinhardtii

Arsenate is a highly toxic element and excessive accumulation of arsenic in the aquatic environment easily triggers a problem threatening the ecological health. Phytoremediation has been widely explored as a method to alleviate As contamination. Here, the green algae, Chlamydomonas reinhardtii was investigated by profiling the accumulation of arsenate and phosphorus, which share the same uptake pathway, in response to arsenic stress. Both C. reinhardtii wild type C30 and the Crpht3 mutant were cultured under arsenic stress, and demonstrated a similar growth phenotype under limited phosphate supply. Sufficient phosphate obviously increased the uptake of polyphosphate and intercellular phosphate in the Crpht3 mutant, which increased the arsenic tolerance of the Crpht3 mutant under stress from 500 µmol L−1 As(V). Upregulation of the PHT3 gene in the Crpht3 mutant increased accumulation of phosphate in the cytoplasm under arsenate stress, which triggered a regulatory role for the differentially expressed genes that mediated improvement of the glutathione redox cycle, antioxidant activity and detoxification. While the wild type C30 showed weak arsenate tolerance because of little phosphate accumulation. These results suggest that the enhanced arsenic tolerance of the Crpht3 mutant is regulated by the PHT3 gene mediation. This study provides insight onto the responsive mechanisms of the PHT3 gene-mediated in alleviating arsenic toxicity in plants.

Crizotinib and its enantiomer suppress ferroptosis by decreasing PE-O-PUFA content

Ferroptosis is a specific form of cell death characterized by excessive accumulation of cellular lipid peroxides. Ferroptosis is closely associated with various diseases, inhibition of which may help alleviate multi-organ injury caused by ischemia-reperfusion and enhance the anti-tumor effect by promoting the immunity of T cells. However, clinical approved drugs targeting ferroptosis process remain rare. In this study, we unexpectedly found that (R)-crizotinib, the first-generation ALK inhibitor, has potent inhibitory activity against ferroptosis across various cell lines. Moreover, its chiral molecule (S)-crizotinib, which was considered to share no common targets with (R)-crizotinib, also suppresses ferroptosis with an efficacy similar to that of (R)-crizotinib. We further demonstrated that both crizotinib enantiomers inhibit ferroptosis independently of their known targets, but through a common mechanism involving the targeting of AGPAT3-mediated synthesis of ether-linked polyunsaturated fatty acids (PE-O-PUFA), which are known to promote lipid-ROS generation and ferroptosis. In line with their activity in cell lines, (R)-crizotinib and (S)-crizotinib effectively mitigate renal ischemia-reperfusion injury in mice. Furthermore, the two compounds also inhibit lipid-ROS accumulation in CD8+ T cells in draining lymph nodes of B16-F10 subcutaneous xenograft mice, thereby promoting anti-tumor effects. Collectively, our study firstly reports a common activity shared by (R)-crizotinib and (S)-crizotinib in ferroptosis regulation. As a clinically approved drug, (R)-crizotinib has well-established pharmacokinetics and safety, which makes it a promising candidate for repurposing. Given the current lack of FDA-approved ferroptosis inhibitors, our findings suggest therapeutically repurposing (R)-crizotinib as well as its enantiomer (S)-crizotinib for treating ferroptosis-related diseases.

Epigallocatechin gallate improves oleic acid-induced hepatic steatosis in laying hen hepatocytes via the MAPK pathway

Fatty liver disease in laying hens, characterized by excessive lipid accumulation in hepatocytes, poses significant challenges to poultry health and production efficiency. In this study, we investigated the therapeutic potential of epigallocatechin gallate (EGCG), a bioactive compound found in green tea, in mitigating oleic acid (OA)-induced hepatic steatosis in primary chicken hepatocytes. Treatment with EGCG effectively attenuated lipid deposition by downregulating lipid synthesis-related genes. Moreover, EGCG mitigated oxidative stress, inflammation, DNA damage, and apoptosis induced by OA, thereby preserving hepatocyte viability. Mechanistically, EGCG exerted its protective effects by modulating the p38 MAPK signaling pathway. Our findings suggest that EGCG holds promise as a therapeutic agent for managing fatty liver disease in poultry, offering insights into novel strategies for improving poultry health and production outcomes.

Enhance the biomethane yield of food waste by anaerobic fermentation

This research investigates optimizing food waste (FW) concentrations for enhanced methane production in anaerobic digestion (AD) systems. Various FW concentrations (10, 20, 30, 40, 50, and 100 % v/v) were assessed for their impact on methane yield, pH stability, volatile fatty acid (VFA) levels, and microbial community composition. The study found that FW concentrations up to 20 % v/v maximized methane production, achieving a peak yield of 140.20 mL CH4/gVS within an ideal pH range of 6.00–7.00. However, higher FW concentrations (>30 % v/v) significantly reduced methane output, with 100 % v/v halting production due to excessive VFA accumulation and pH drops. Key microbial players included acetoclastic methanogens like Methanosaeta and hydrogenotrophic methanogens such as Methanospirillum. These findings emphasize the importance of managing FW concentrations to maintain AD system efficiency, providing valuable insights into sustainable waste management and renewable energy production.

Effect of Nidra on Meda Dhatu with special reference to Different Dehaprakriti

According to Ayurveda, sleep is included in Upastambha Traya, Adharaniya Vega hence it sustains life. Getting enough Nidra helps in maintaining normal growth and development of the body. According to Ayurveda, improper sleep (Nidra Viparyaya) may cause some life style diseases (Sthaulya). So, it can be said that abnormal, inadequate Nidra can make a person Atura (diseased). Among the seven Dhatus, Meda with Jala and Prithvi as its dominant elements, is solid and soft. It is the storage site for excess fat in the body. Definition of Swastha also refers to the moderate quantity of the seven Dhatus of the body. Disorders may develop if there is variation in it. In this context, the excess accumulation of Meda Dhatu that is Medo Vruddhi results in overweight/obesity and decrease in Meda Dhatu that is Meda Kshaya results in underweight. Nidra has such inevitable effects on mind and body. In Ayurveda, Acharya Charak has stated in Charak Sutrasthan, Adhyay 21/51 “Swapnahar Samutthe Cha Sthaulya Karshye Visheshatah” that means Aahar and Nidra are the main causes for Sthaulya and Karshya. Also, modern science has stated that sleep requirement is not constant but has to be taken as per the persons need. Therefore, to sum up, In, today’s era, sleep is seen to be majorly disturbed which is one of the reasons for psychosomatic disorders. There is disturbed fat distribution observed in people surrounding us with no major co-morbidity but still showing symptoms related to Meda Dhatu. Therefore, to reveal the role of Nidra to cause the improper Meda dhatu distribution in body So, this study is being carried to explore the effect of Nidra on Meda Dhatu with special reference to different Deha Prakriti.