Reduce Cell Damage Research Articles

VvJAZ13 Positively Regulates Cold Tolerance in Arabidopsis and Grape.

Cold stress adversely impacts grape growth, development, and yield. Therefore, improving the cold tolerance of grape is an urgent task of grape breeding. The Jasmonic acid (JA) pathway responsive gene JAZ plays a key role in plant response to cold stress. However, the role of JAZ in response to low temperatures in grape is unclear. In this study, VvJAZ13 was cloned from the 'Pinot Noir' (Vitis vinefera cv. 'Pinot Noir') grape, and the potential interacting protein of VvJAZ13 was screened by yeast two-hybrid (Y2H). The function of VvJAZ13 under low temperature stress was verified by genetic transformation. Subcellular localization showed that the gene was mainly expressed in cytoplasm and the nucleus. Y2H indicated that VvF-box, VvTIFY5A, VvTIFY9, Vvbch1, and VvAGD13 may be potential interacting proteins of VvJAZ13. The results of transient transformation of grape leaves showed that VvJAZ13 improved photosynthetic capacity and reduced cell damage by increasing maximum photosynthetic efficiency of photosystem II (Fv/Fm), reducing relative electrolyte leakage (REL) and malondialdehyde (MDA), and increasing proline content in overexpressed lines (OEs), which played an active role in cold resistance. Through the overexpression of VvJAZ13 in Arabidopsis thaliana and grape calli, the results showed that compared with wild type (WT), transgenic lines had higher antioxidant enzyme activity and proline content, lower REL, MDA, and hydrogen peroxide (H2O2) content, and an improved ability of scavenging reactive oxygen species. In addition, the expression levels of CBF1-2 and ICE1 genes related to cold response were up-regulated in transgenic lines. To sum up, VvJAZ13 is actively involved in the cold tolerance of Arabidopsis and grape, and has the potential to be a candidate gene for improving plant cold tolerance.

Anti-inflammatory mechanism of the non-volatile ingredients originated from Guanghuoxiang () based on high performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope and cell metabolomics.

To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli. High performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope (HPLC-HESI-HRMS) was used to analyze the chemical constituents of the non-volatile ingredients of patchouli. The anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide (LPS) induced RAW264.7 cell inflammation model, and the anti-inflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics. The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS, and 36 flavonoids and 18 other components were identified. These ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells, but also regulated the expression levels of arginine, L-leucine, cholesterol, fructose and sorbitol by down-regulating arginine metabolism, aminoacyl-tRNA biosynthesis, polyol/sorbitol pathway, so as to reduce inflammation and reduce cell damage. The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.

Naringenin Alleviates Radiation-Induced Intestinal Injury by Inhibiting TRPV6 in Mice.

Naringenin (NAR) possesses unique anti-inflammatory, antiapoptosis effects and various bioactivities; however, its role against radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate whether NAR has protective effects against radiation-induced intestinal injury and the underlying mechanisms. C57BL/6J mice are exposed to a single dose of 13Gy X-ray total abdominal irradiation (TAI), then gavaged with NAR for 7 days. NAR treatment prolongs the survival rate, protects crypts and villi from damage, alleviates the level of radiation-induced inflammation, and mitigates intestinal barrier damage in the irradiated mice. Additionally, NAR reduces immune cell infiltration and intestinal epithelial cell apoptosis. NAR also shows radioprotective effects in human colon cancer cells (HCT116) and human intestinal epithelial cells (NCM460). It reduces cell damage by reducing intracellular calcium ion levels and reactive oxygen species (ROS) levels. NAR-mediated radioprotection is associated with the downregulation of transient receptor potential vanilloid 6 (TRPV6), and inhibition of apoptosis pathway. Notably, treatment with NAR fails to further increase the protective effects of the TRPV6 inhibitor 2-APB, indicating that TRPV6 inhibition is essential for NAR activity. NAR inhibits the apoptosis pathway by downregulating TRPV6 and reducing calcium ion level, thereby alleviating RIII. Therefore, NAR is a promising therapeutic drug for RIII.

TaGSK3 regulates wheat development and stress adaptation through BR-dependent and BR-independent pathways.

The GSK3/SHAGGY-like kinase plays critical roles in plant development and response to stress, but its specific function remains largely unknown in wheat (Triticum aestivum L.). In this study, we investigated the function of TaGSK3, a GSK3/SHAGGY-like kinase, in wheat development and response to stress. Our findings demonstrated that TaGSK3 mutants had significant effects on wheat seedling development and brassinosteroid (BR) signalling. Quadruple and quintuple mutants showed amplified BR signalling, promoting seedling development, while a sextuple mutant displayed severe developmental defects but still responded to exogenous BR signals, indicating redundancy and non-BR-related functions of TaGSK3. A gain-of-function mutation in TaGSK3-3D disrupted BR signalling, resulting in compact and dwarf plant architecture. Notably, this mutation conferred significant drought and heat stress resistance of wheat, and enhanced heat tolerance independent of BR signalling, unlike knock-down mutants. Further research revealed that this mutation maintains a higher relative water content by regulating stomatal-mediated water loss and maintains a lower ROS level to reduces cell damage, enabling better growth under stress. Our study provides comprehensive insights into the role of TaGSK3 in wheat development, stress response, and BR signal transduction, offering potential for modifying TaGSK3 to improve agronomic traits and enhance stress resistance in wheat.

Evaluation of antimicrobial, anticancer, antidiabetic, antioxidant activities and silver nanoparticles synthesized from Indian Clove- Syzygium aromaticum leaf extract

The Indian Clove (Syzygium aromaticum) is a naturally occurring spice with significant biological properties. It is primarily found in India and Indonesia, but can also be cultivated in other coastal areas. Clove is commonly used as a natural preservative and in the production of natural medicines. One of the notable benefits of clove is its ability to help treat diseases caused by various bacteria and fungi, including E. coli, P. aeruginosa, S. aureus, Z. mobilis, and C. albicans. Additionally, clove possesses antioxidant properties that can help reduce cell damage caused by free radicals. Clove has also shown potential in inhibiting the growth of cancer cells and reducing the activity of enzymes such as amylase, glucosidase, and lipase, which can be beneficial for managing diabetes. The study demonstrated that Silver nanoparticles (AgNPs) synthesized from Indian clove leaf extract exhibited promising antimicrobial, anticancer, antidiabetic, and antioxidant activities. This suggests that these nanoparticles could have versatile applications in antimicrobial therapy, cancer treatment, diabetes management, and antioxidant supplementation. However, further research is needed to understand the underlying mechanisms of these activities and to evaluate the safety and efficacy of these nanoparticles in more complex biological systems. In summary, clove possesses diverse biological properties and has potential applications in various therapeutic areas. The synthesis of AgNPs from clove leaf extract shows promise in multiple fields, but more research is required for a deeper understanding of its mechanisms and broader applications.

Green cocoon-derived sericin reduces cellular damage caused by radiation in human keratinocytes

Radiation therapy used in the treatment of cancer causes skin damage, and no method of care has been established thus far. Recently, it has become clear that sericin derived from silkworm cocoons has moisturizing and antioxidant functions. In addition, green cocoon-derived sericin, which is rich in flavonoids, may have enhanced functions. However, whether this green cocoon-derived sericin can reduce radiotherapy-induced skin damage is unclear. In the present study, we aimed at establishing care methods to reduce skin cell damage caused by X-irradiation using green cocoon-derived sericin. We investigated its effect on human keratinocytes using lactate dehydrogenase activity to indicate damage reduction. Our results showed that green cocoon-derived sericin reduced cell damage caused by X-irradiation. However, this effect was not observed when cells were treated before X-irradiation or with a sericin derived from white cocoons. In addition, green cocoon-derived sericin decreased the levels of reactive oxygen species and lipid peroxidation. Our results suggest that green cocoon sericin mitigates the damaging effect of X-irradiation on cells, hence presenting potential usefulness in reducing skin damage from radiation therapy and opening new avenues in the care of cancer patients.

Improvement of biochemical and antioxidant responses of borage (Borago officinalis L.) under drought stress conditions with the use of vermicompost and zinc sulfate.

Drought poses a significant threat to crop production systems. Therefore, this study aimed to investigate the impact of vermicompost and foliar application of zinc sulfate under conditions of reduced irrigation on the physiological properties of Borage. A two-year experiment was conducted following a split factorial design within a randomized complete block design with three replications at Yasouj University Research Station in 2017 and 2018. The primary factor involved three levels of irrigation cut-off (I1: full irrigation, I2: irrigation cut-off at the flowering stage, and I3: irrigation cut-off during the seed-filling stage). The sub-factor included vermicompost fertilizer at three different levels (N0: control, N1: 5tonha-1, and N2: 10tonha-1), and foliar application of zinc sulfate at three levels (Z0: control, Z1: 2 and Z2: 4mgl-1). During the flowering stage stress, foliar application of 4mgl-1 of zinc sulfate resulted in an increased chlorophyll a + b content in plants (2.91mgg-1FW), while the control showed the lowest amount (2.56mgg-1FW). Vermicompost supplementation improved chlorophyll a + b content during the seed-filling stage under conditions of irrigation cut-off. The results indicated that an increase in vermicompost fertilizer application led to an elevation in relative water content (RWC), with the highest RWC (79.2%) achieved when 10tonha-1 of vermicompost was applied. Irrigation cut-off during the seed-filling stage resulted in increased electrolyte leakage and higher fertilizer usage, thus reducing cell damage. Furthermore, the findings revealed that applying 2 and 4mgl-1 zinc sulfate reduced malondialdehyde content by 5% and 9%, respectively. The catalase, peroxidase, and superoxide dismutase activities demonstrated an increased response to stress mitigation treatments. However, their activities decreased as vermicompost and zinc sulfate levels increased. The study demonstrated that the highest biomass was obtained when 10tonha-1 of vermicompost and 2mgl-1 of zinc sulfate were applied. The flowering stage of the plant exhibited the most significant negative impact under stress conditions. Nonetheless, using vermicompost and zinc sulfate, particularly during the seed-filling phase, alleviated the adverse effects of drought stress. In conclusion, our findings indicate that, although drought stress resulted in increased electrolyte leakage due to elevated free radical production, vermicompost, and zinc sulfate played a role in reducing stress.

PEDOT:PSS-coated platinum electrodes for neural stimulation

Safe and long-term electrical stimulation of neurons requires charge injection without damaging the electrode and tissue. A common strategy to diminish adverse effects includes the modification of electrodes with materials that increases the charge injection capacity. Due to its high capacitance, the conducting polymer PEDOT:PSS is a promising coating material; however, the neural stimulation performance in terms of stability and safety remains largely unexplored. Here, PEDOT:PSS-coated platinum (Pt-PEDOT:PSS) microelectrodes are examined for neural stimulation and compared to bare platinum (Pt) electrodes. Microelectrodes in a bipolar configuration are used to deliver current-controlled, biphasic pulses with charge densities ranging from 64 to 255 μC cm−2. Stimulation for 2 h deteriorates bare Pt electrodes through corrosion, whereas the PEDOT:PSS coating prevents dissolution of Pt and shows no degradation. Acute stimulation of primary cortical cells cultured as neurospheres shows similar dependency on charge density for Pt and Pt-PEDOT:PSS electrodes with a threshold of 127 μC cm−2 and increased calcium response for higher charge densities. Continuous stimulation for 2 h results in higher levels of cell survival for Pt-PEDOT:PSS electrodes. Reduced cell survival on Pt electrodes is most profound for neurospheres in proximity of the electrodes. Extending the stimulation duration to 6 h increases cell death for both types of electrodes; however, neurospheres on Pt-PEDOT:PSS devices still show significant viability whereas stimulation is fatal for nearly all cells close to the Pt electrodes. This work demonstrates the protective properties of PEDOT:PSS that can be used as a promising approach to extend electrode lifetime and reduce cell damage for safe and long-term neural stimulation.

Salvianolic acid B promotes angiogenesis and inhibits cardiomyocyte apoptosis by regulating autophagy in myocardial ischemia

BackgroundMyocardial ischemia (MI) can cause angina, myocardial infarction, and even death. Angiogenesis is beneficial for ensuring oxygen and blood supply to ischemic tissue, promoting tissue repair, and reducing cell damage. In this study, we evaluated the effects of Salvianolic acid B (Sal B) against myocardial ischemia and explored its underlying mechanism on autophagy.MethodsThe anti-apoptosis effect of Sal B was conducted by staining Annexin V-FITC/PI and Hoechst as well as evaluating apoptosis bio-markers at protein level in H9c2 cells at glucose deprivation condition. HUVECs were co-cultured with H9c2, and the tube formation assay was used to monitor Sal B’s impact on angiogenesis. The MI model of mice was induced by intraperitoneal injection of isoproterenol (ISO). The effect of Sal B on MI mice was evaluated by HE, Masson, immunohistochemistry, WB and kits. In addition, Atg5 siRNA was applied to verify whether the protective effect of Sal B was regulated to autophagy.ResultsIn H9c2, Sal B reduced the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA) and reactive oxygen species (ROS), improved the levels of superoxide dismutase (SOD) and mitochondrial membrane potential, downregulated the expressions of Bax and cleaved-Caspase3, upregulated the expression of Bcl-2. Therefore, Sal B could significantly inhibit the damage of H9c2 caused by glucose deprivation. In the co-culture system of H9c2 and HUVECs, vascular endothelial growth factor (VEGF) level in the supernatant was dramatically raised by Sal B. Sal B upregulated the expressions of VEGF, platelet derived growth factor (PDGF) and endothelial marker CD31. It implied that Sal B exerted a significant pro-angiogenic effect. Moreover, Sal B increased the expression of LC3, Atg5, and Beclin1, while reducing the level of P62. When the expression of Atg5 was inhibited, the protective effects of Sal B on apoptosis and angiogenesis was reversed.ConclusionsSal B inhibited cardiomyocyte apoptosis and promoted angiogenesis by regulating autophagy, thereby improving MI.

Puerarin reduces cell damage from cerebral ischemia-reperfusion by inhibiting ferroptosis

This study explores the protective effects of Puerarin, a compound derived from the traditional Chinese herb Pueraria, against cellular damage induced by Oxygen-Glucose Deprivation/Reoxygenation (OGD/R) in PC12 cells. The research focuses on understanding how Puerarin influences the mechanisms of ferroptosis and oxidative stress, key factors in ischemia-reperfusion injury relevant to neurodegenerative diseases. In our in vitro model, we identified the optimal OGD duration to induce significant cell stress and confirmed the non-toxicity of Puerarin up to 100uM. The results reveal that Puerarin substantially mitigates the detrimental effects of OGD/R, including improvements in cell viability, mitochondrial integrity, and reductions in oxidative stress markers like ROS and lipid peroxidation. Notably, Puerarin modulates key proteins in the autophagy process and the Nrf2 pathway, crucial in cellular stress responses. Further, the use of 3-Methyladenine, an autophagy inhibitor, underscores the significance of autophagy in managing OGD/R-induced stress. These findings suggest Puerarin's potential as a therapeutic agent for conditions characterized by ischemic cellular damage, highlighting the need for further clinical exploration.

Serum Copper, Iron, and Total Iron Binding Capacity in Hypothyroidism: A Case Control Study

Background: Thyroid hormone metabolism is linked to iron metabolism. Thyroperoxidase, a key enzyme in the biosynthesis of thyroid hormones, is iron-dependent. Thus, iron deficiency might be the primary cause of hypothyroidism. Copper is another trace element that has been linked to thyroid status. Copper regulates excessive thyroxine (T4) absorption and reduces cell damage during thyroid hormone synthesis. The present study clarified the possible correlations between iron and copper levels as well as total iron binding capacity (TIBC) and triiodothyronine (T3), T4, as well as thyroid-stimulating hormone (TSH) levels in healthy and hypothyroid subjects.Materials and methods: Thirty-five healthy subjects and 35 hypothyroid subjects were included in this study. Serum T3, T4, and TSH levels were measured using the enzyme linked fluorescence assay. Serum iron levels and TIBC were estimated using ferrozine/magnesium carbonate method, while serum copper levels were estimated using colorimetric method.Results: Copper levels were not significantly different between healthy and hypothyroid subjects. Iron and T4 levels were significantly lower in hypothyroid subjects compared with those in healthy subjects, while TIBC and TSH levels were significantly higher. There was no significant correlation between copper levels and T3, T4, and TSH levels.Conclusion: There were inverse correlations between TIBC and T4 as well as iron levels, and there was no significant correlation between copper levels and all thyroid function parameters. Routine examination of iron levels and thyroid function is highly recommended for early diagnosis and therapy of hypothyroidism.Keywords: total iron binding capacity, iron, copper, hypothyroidism

Promotion of Ca2+ Accumulation in Roots by Exogenous Brassinosteroids as a Key Mechanism for Their Enhancement of Plant Salt Tolerance: A Meta-Analysis and Systematic Review.

Brassinosteroids (BRs), the sixth major phytohormone, can regulate plant salt tolerance. Many studies have been conducted to investigate the effects of BRs on plant salt tolerance, generating a large amount of research data. However, a meta-analysis on regulating plant salt tolerance by BRs has not been reported. Therefore, this study conducted a meta-analysis of 132 studies to elucidate the most critical physiological mechanisms by which BRs regulate salt tolerance in plants from a higher dimension and analyze the best ways to apply BRs. The results showed that exogenous BRs significantly increased germination, plant height, root length, and biomass (total dry weight was the largest) of plants under salt stress. There was no significant difference between seed soaking and foliar spraying. However, the medium method (germination stage) and stem application (seedling stage) may be more effective in improving plant salt tolerance. BRs only inhibit germination in Solanaceae. BRs (2 μM), seed soaking for 12 h, and simultaneous treatment with salt stress had the highest germination rate. At the seedling stage, the activity of Brassinolide (C28H48O6) was higher than that of Homobrassinolide (C29H50O6), and post-treatment, BRs (0.02 μM) was the best solution. BRs are unsuitable for use in the germination stage when Sodium chloride is below 100 mM, and the effect is also weakest in the seedling stage. Exogenous BRs promoted photosynthesis, and antioxidant enzyme activity increased the accumulation of osmoregulatory and antioxidant substances and reduced the content of harmful substances and Na+, thus reducing cell damage and improving plant salt tolerance. BRs induced the most soluble protein, chlorophyll a, stomatal conductance, net photosynthetic rate, Glutathione peroxidase, and root-Ca2+, with BRs causing Ca2+ signals in roots probably constituting the most important reason for improving salt tolerance. BRs first promoted the accumulation of Ca2+ in roots, which increased the content of the above vital substances and enzyme activities through the Ca2+ signaling pathway, improving plant salt tolerance.

Genome-scale reconstruction of the metabolic network in Streptococcus thermophilus S-3 and assess urea metabolism.

Streptococcus thermophilus is an important strain widely used in dairy fermentation, with distinct urea metabolism characteristics compared to other lactic acid bacteria. The conversion of urea by S. thermophilus has been shown to affect the flavor and acidification characteristics of milk. Additionally, urea metabolism has been found to significantly increase the number of cells and reduce cell damage under acidic pH conditions, resulting in higher activity. However, the physiological role of urea metabolism in S. thermophilus has not been fully evaluated. A deep understanding of this metabolic feature is of great significance for its production and application. Genome-scale metabolic network models (GEMs) are effective tools for investigating the metabolic network of organisms using computational biology methods. Constructing an organism-specific GEM can assist us in comprehending its characteristic metabolism at a systemic level. In the present study, we reconstructed a high-quality GEM of S. thermophilus S-3 (iCH492), which contains 492 genes, 608 metabolites and 642 reactions. Growth phenotyping experiments were employed to validate the model both qualitatively and quantitatively, yielding satisfactory predictive accuracy (95.83%), sensitivity (93.33%) and specificity (100%). Subsequently, a systematic evaluation of urea metabolism in S. thermophilus was performed using iCH492. The results showed that urea metabolism reduces intracellular hydrogen ions and creates membrane potential by producing and transporting ammonium ions. This activation of glycolytic fluxes and ATP synthase produces more ATP for biomass synthesis. The regulation of fluxes of reactions involving NAD(P)H by urea metabolism improves redox balance. Model iCH492 represents the most comprehensive knowledge-base of S. thermophilus to date, serving as a potent tool. The evaluation of urea metabolism led to novel insights regarding the role of urease. © 2023 Society of Chemical Industry.

Effect of fatty acids on intracellular pneumocandin B0 storage in the fermentation of Glarea lozoyensis

The natural product pneumocandin B0 is the precursor of the antifungal drug caspofungin. To explore the relationship between pneumocandin B0 and oil. We found that the addition of 1 g/L of oil to the fermentation medium is more conducive to the production of pneumocandin B0. The metabolic reaction mechanism was explored using different fatty acids and the results showed that stearic acid and acetic acid increased the total production of pneumocandin B0 by 22.98% and 9.08%, respectively, as well as increasing the content of intracellular lipid droplets. We also analyzed gene expression and pathway differences between the two different fatty acids using transcriptome analyses. The addition of both acetic acid and stearic acid promoted an active pentose phosphate pathway, providing cells with higher intracellular reducing power. We found that the addition of fatty acids can lead to lipid accumulation, and lipid droplets can sequester lipophilic secondary metabolites such as pneumocandin B0 to reduce cell damage. These results provide novel insights into the relationship between pneumocandin B0 biosynthesis and fatty acids in G. lozoyensis. In addition, this study provides important genetic information for improving the yield of pneumocandin B0 through a strategy of metabolic engineering in the future.Graphical

Multifaceted synergistic facilitation mechanism of conductive polymers in promoting selenite bioreduction and biological detoxification

Here, polypyrrole (PPY) was first used to the bioreduction of toxic selenite, while the acceleration effect and mechanism were explored. Experiment results suggested that PPY could enhance the selenite bioreduction from 0.42 to 1.04 mg/(L·h). The tests of electrochemical analysis and cytochrome c (cyt-c) content confirmed that PPY promoted the intracellular/intracellular electron transfer of Shewanella oneidensis·MR-1 in selenite bioreduction process. The enhancement of metabolic activity by PPY contributed to biological detoxification, which was manifested in the increased extracellular polymeric substances (EPS), adenosine triphosphate (ATP), electron transfer system activity (ETSA), membrane permeability and enzyme activity. Transcriptome analysis of DEGs, KEGG pathway enrichment and GO functional classification verified that the environmental adaptability of Shewanella oneidensis·MR-1 was enhanced with the addition of PPY. The transmission electron microscopy (TEM) images indicated that PPY promoted the biosynthesis of selenium nanoparticles (SeNPs), which was beneficial to reduce cell damage. Combined with the above results, a multifaceted synergistic facilitation mechanism based on “conductive cross-linking network” was elaborated from electron transfer, microbial metabolism and environmental adaptability. This study shed light the effect of conductive polymers (CPs) on selenite bioreduction and provided new insights into the bioremediation of toxic pollutants.

Surface tension-induced biomimetic assembly of cell-laden fibrous bundle construct for muscle tissue engineering.

The field of tissue engineering has been long seeking to develop functional muscle tissue that closely resembles natural muscle. This study used a bio-inspired assembly based on the surface tension mechanism to develop a novel method for engineering muscle tissue. This approach enabled uniaxially ordered electrospun fibers to naturally collide into an aligned bundle without the need for manual handling, thereby reducing cell damage during the cell culture procedure. During the assembly procedure, C2C12 myoblasts were cultured in a viscous collagen hydrogel that caused wetting while providing adequate structural stability for the cell-fiber construct. In addition, gene expression analysis of the resulting muscle-like fibril bundle revealed improved myogenic differentiation. These findings highlight the potential of using a collagen hydrogel and the surface tension mechanism to construct biologically relevant muscle tissue, offering a promising strategy that may outperform existing approaches. Overall, this study contributes to the development of advanced tissue engineering methods and brings us a step closer to creating functional muscle tissue for therapeutic and regenerative medicine applications.

Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway

Objective: To explore the regulatory mechanism of transient receptor potential melastatin-7 (TRPM7) in high glucose-induced renal tubular epithelial cell injury. Methods: The expression of TRPM7 in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells was detected by RT-qPCR. Then, the TRPM7 interference vector was constructed, and the downstream high mobility group box 1 (HMGB1)/Toll-like receptor 4 (TLR4) signaling pathway proteins were detected. Next, in addition to interference with TRPM7 expression, overexpression of HMGB1 in high glucose-induced HK-2 cells was performed. Cell activity, apoptosis, oxidative stress levels, and inflammation levels were determined by CCK8, TUNEL, Western blotting, immunofluorescence and related kits. Results: TRPM7 expression was upregulated in the serum of diabetic nephropathy patients and high glucose-induced HK-2 cells. Interference with TRPM7 reduced cell damage, epithelial-mesenchymal transition, oxidative stress, and inflammatory response in high glucose-induced HK-2 cells via inhibiting the HMGB1/TLR4 signaling pathway. However, the effects induced by TRPM7 silencing were abrogated by HMGB1 overexpression. Conclusions: Decreased TRPM7 alleviates high glucose-induced renal tubular epithelial cell injury by inhibiting the HMGB1/TLR4 signaling pathway. Further animal experiments and clinical trials are warranted to verify its effect.

Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy

Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.

Inhibition of SK2 and ER stress ameliorated inflammation and apoptosis in liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) remains a major cause of mortality and morbidity after liver surgery. Endoplasmic reticulum (ER) stress is a critical mechanism of inflammatory injury during hepatic IRI. In this study, we investigated the effect of sphingosine kinases 2 (SK2) on ER stress and hepatic IRI. We established hepatic IRI mice and hepatocellular hypoxia/reoxygenation in vitro model. We observed the SK2 and ER stress protein IRE1α expression. Then, we used an SK2 inhibitor and knocked down IRE1α/SK2, to observe the effect of SK2 during IRI. Our results showed that the expression of ER stress and SK2 was significantly elevated during hepatic IRI. Inhibition of SK2 ameliorated liver inflammation and reduced cell apoptosis in hepatic IRI mice. Consistently, we found that the inhibition of IRE1α also downregulated SK2 expression and reduced mitochondrial membrane permeability. Furthermore, the knockdown of SK2 could also reduce cell damage and reduce the expression of inflammatory factors but did not influence ER stress-related signaling pathway. Taken together, our results suggested that ER stress and SK2 played important and regulatory roles in hepatic IRI. Inhibition of ER stress and SK2 could significantly improve liver function after hepatic IRI.

Antiparkinsonian effects of Indian spice Amomum subulatum fruit extract by modulating the behavioural, inflammatory markers, antioxidant, and histopathology parameters in rats

Parkinson's disease (PD) is a complex neurodegenerative disorder associated with the loss of dopaminergic neurons in the substantia nigra followed by dopamine depletion in the striatum. PD usually affects people over 50; when those under 50 are involved, it is generally referred to as early-onset PD. The present study aimed to understand and explain the role of the typical Indian spice, greater cardamom, against parkinsonism and related complications. The methanolic extract of Amomum subulatum has flavonoids as the major phytoconstituent and may be a beneficial adjuvant in treating PD. Amomum subulatum fruit extract (ASFE) was given as treatment to the rats at 100 mg/kg and 200 mg/kg. Symptoms of Parkinson’s disease, such as tremors, muscular rigidity, catalepsy, locomotor activity, and grip strength, were examined by several behavioural tests. Treatment with ASFE showed a significant decrease in all the symptoms of PD. Enzyme assays revealed a reduction in the levels of antioxidant enzymes SOD, Catalase, and GSH after administering reserpine and increased levels after treating ASFE. ASFE causes dopaminergic neuron regeneration after reserpine induces injury, thus increasing dopamine levels and restoring cellular damage. The inflammatory biomarkers revealed decreased proinflammatory cytokines such as TNF-α and IL-6. In contrast, increase in the level of IL-10, which is an anti-inflammatory cytokine. The histopath studies showed reduced cell damage occurring in PD after the treatment with ASFE. The present investigation highlights the role of greater cardamom from the Indian kitchen to ethnopharmacology in progressive neurological degeneration.