Protective Effect Research Articles

Assessment of the developmental toxicity of acrylamide in albino rats and the possible protective effect of vitamin E: A morphological animal study

Acrylamide (ACR) is a known neurotoxin and carcinogen linked to frying and baking meals high in carbohydrates and is frequently present in soils and groundwater. It is used to create polymers for industry. Pregnant women are exposed to ACR through food, and their fetuses likely to be harmed. Vitamin E is significant lipid-soluble vitamin found in nature and essential for numerous physiological activities. Aim: to examine effects of exposure to acrylamide on skeletal development of rat embryos and the potential role of Vitamin E (Vit. E) in the reduction of these effects. Forty pregnant albino rats were divided into four groups. Control group was administrated distilled water orally. Low ACR group was administrated acrylamide (10 mg/kg/day) via gavage from GD 1 to GD20. High ACR group was administrated acrylamide (30 mg/kg/day) from GD 1 to GD 20. ACR vit. E group was administrated 100 mg/kg of vitamin E and 30 mg/kg of ACR orally. Alizarin red and Alcian blue stains were used to double-stain the skeletons, then examined by dissecting stereomicroscope. Skeletal anomalies found were incomplete and un-ossified bones of the skull, sacral vertebrae, ribs, bones of forelimb and hind limb, unossified carpals, metacarpals, tarsals, metatarsals, and phalanges. These were obvious in ACR-treated groups compared to the control group and improved in ACR vitamin E group. Acrylamide caused skeletal congenital abnormalities, thus proving its teratogenicity, and vitamin E seems to protect against and reduce such abnormalities.

Schistosoma japonicum cystatin has protective effects against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.

To evaluate the protective effect of Schistosoma japonicum cystatin (rSj-Cystatin) in a mouse mode of "two-hit" sepsis. Sixty male C57BL/6 mice randomized equally into sham-operated group, protein group, "two-hit" modeling group, and protein intervention group. In the former two groups, the mice received an intraperitoneal injection of 100 μL PBS followed by exposure of the cecum and then by intraperitoneal injection of 100 μL PBS or 25 μg rSj-Cystatin 30 min later; In the latter two groups, 100 μL PBS containing LPS (5 mg/kg) was injected intraperitoneally 24 h before cecal ligation and puncture (CLP), and 100 μL PBS or 25 μg rSj-Cystatin were injected 30 min after CLP. At 12 h after rSj-Cystatin treatment, 6 mice from each group were sacrificed for detection of TNF-α, IL-6, IL-10, TGF-β, iNOS and Arg-1 in the serum, spleen, liver, lung and kidney tissues using ELISA, for examinations of liver, lung and kidney pathologies with HE staining, and for analysis of CD3+CD4+CD25+Foxp3+ T cell percentage in the spleen using flow cytometry. The remaining mice were observed for general condition and 72-h survival. The 72-h survival rates in the 4 groups were 100%, 100%, 0% and 20%, respectively, showing significant differences between the latter two groups. The mouse models of "two-hit" sepsis exhibited obvious tissue pathologies and significant elevations of TNF-α and IL-6 in both the serum and tissue homogenate, which were significantly ameliorated by rSj-Cystatin treatment. Treatment with rSj-Cystatin also increased IL-10 and TGF-β levels and spleen CD3+CD4+CD25+Foxp3+ T cell percentage. The septic mouse models also showed increased iNOS levels in all the detected tissues and a decreased Arg-1 level in the kidney, and these changes were obviously improved by rSj-Cystatin treatment. rSj-Cystatin has a protective effect against "two-hit" sepsis in mice by regulating the inflammatory microenvironment.

Yiqi Yangyin Huazhuo Tongluo Formula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

To investigate the protective effect of Yiqi Yangyin Huazhuo Tongluo Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism. Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting. Autophagic activity in the cells were evaluated with MDC staining. The effect of miR-21a-5p mimic on FoxO1 transcription and the binding of miR-21a-5p to FoxO1 were examined with luciferase reporter gene assay and radioimmunoprecipitation assay. MPC5 cells exposed to high glucose showed significantly increased miR-21a-5p expression, lowered expressions of FoxO1, PINK1, and Parkin1 mRNAs, and reduced levels of FoxO1, PINK1, parkin, nephrin, and podocin proteins and autophagic activity. Treatment of the exposed cells with YYHT-medicated sera and miR-21a-5p inhibitor both significantly enhanced the protein expressions of nephrin and podocin, inhibited the expression of miR-21a-5p, increased the mRNA and protein expressions of FoxO1, PINK1 and Parkin, and upregulated autophagic activity of the cells. Transfection with miR-21a-5p mimic effectively inhibited the transcription of FoxO1 and promoted the binding of miR-21a-5p to FoxO1 in MPC5 cells, and these effects were obviously attenuated by treatment with YYHT-medicated sera. YYHT-medicated sera alleviate high glucose-induced injury in MPC5 cells by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.

Anemonin suppresses sepsis‐induced acute lung injury by inactivation of nuclear factor‐kappa B and activation of nuclear factor erythroid 2‐related factor‐2/heme oxygenase‐1 pathway

AbstractSepsis‐induced acute lung injury (ALI) is a common acute and severe reason of death in the intensive care unit. Although the pathogenesis is complicated and multifactorial, elevated inflammation and oxidative stress are considered as fundamental mechanisms for the progression of ALI. Anemonin is a natural compound with diverse biological properties including anti‐inflammatory and anti‐oxidative effects. To identify whether anemonin has protective effects on sepsis‐induced ALI, a mouse sepsis‐induced ALI model and cellular models using the mouse alveolar macrophage MH‐S cells and mouse lung epithelial MLE‐12 cells were established. Our results showed that anemonin reduced lipopolysaccharide (LPS)‐induced mortality, and improved sepsis‐induced ALI in the mouse model, as shown by improved histopathological changes, decreased lung wet/dry weight ratio, and myeloperoxidase activity. Anemonin alleviated LPS‐induced secretion of tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), and interleukin‐6 (IL‐6) in bronchoalveolar lavage fluid samples, as well as reversed the LPS‐caused increase in malondialdehyde (MDA) content and decrease in activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) in lung tissues. In the cellular model, anemonin inhibited the LPS‐induced inflammatory responses and oxidative stress in MH‐S and MLE‐12 cells. In addition, anemonin inhibited LPS‐induced nuclear factor‐kappa B (NF‐κB) pathway, while enhancing the activation of nuclear factor erythroid 2‐related factor‐2 (Nrf2) in lung tissues, MH‐S, and MLE‐12 cells. NF‐κB inhibition enhanced the anti‐inflammatory and anti‐oxidative effects of anemonin, while Nrf2 knockdown attenuated these effects of anemonin, implying the critical roles of NF‐κB and Nrf2. These results indicated that anemonin suppressed sepsis‐induced acute lung injury by inhibition of NF‐κB and activation of Nrf2/heme oxygenase‐1 pathway, suggesting that anemonin might be developed as a new therapeutic agent for the treatment of sepsis‐induced ALI.

X-ray Responsive Antioxidant Drug-Free Hydrogel for Treatment of Radiation Skin Injury.

Radiotherapy (RT) is widely applied in tumor therapy, but inevitable side effects, especially for skin radiation injury, are still a fatal problem and life-threatening challenge for tumor patients. The main components of topical radiation protection preparations currently available on the market are antioxidants, such as SOD, which are limited by their unstable activity and short duration of action, making it difficult to achieve the effects of radiation protection and skin radiation damage treatment. Therefore, we designed a drug-free antioxidant hydrogel patch with encapsulated bioactive epidermal growth factor (EGF) for the treatment of radiation skin injury. The X-ray responsive hydrogel formed by copolymerization of the disulfide-containing hyperbranched poly(β-hydrazide ester) macromer polymer (PBAE), methacryloylated hyaluronic acid, and acrylamide exhibits continuous antioxidant activity through the oxidation of disulfide bonds in PBAE as well as the triggered release of EGF after X-ray responsive breakage of the polymer network to finally promote radioactive wound healing. Upon radiotherapy, the antioxidant hydrogel is able to alleviate local oxidative stress by continuously eliminating excessive ROS and can prevent deterioration of radiation skin injury. Moreover, the drug-free hydrogel with its excellent antioxidant property can overcome the disadvantages of traditional medicine (such as poor solubility, random diffusion, rapid drug clearance, and interference with tumor efficacy). Notably, the drug-free hydrogel exhibits a negligible effect for tumor therapy because the antioxidant hydrogel acts only on the epidermis and displays no shielding effect for ionization radiation. Ultimately, in vivo animal studies affirm the efficacy of our methodology, wherein the administration of the antioxidant hydrogel on acute irradiated skin attenuates the progression of radiation skin injury and promotes radioactive wound healing. This innovative strategy points out a new inspiration for the precise treatment of skin radiation damage with X-ray responsive antioxidant drug-free hydrogels.

Evaluation of UV-A and UV-B transmission through the windows of gas, hybrid, and electric vehicles

UV-A exposure is a major risk factor for melanoma, nonmelanoma skin cancer, photoaging, and exacerbation of photodermatoses. Since people spend considerable time in cars daily, inadequate UV-A attenuation by car windows can significantly contribute to the onset or exacerbation of these skin diseases. Given recent market trends in the automobile industry and known impact of car windows on cumulative lifelong UV damage to the skin, there is a need to comparatively evaluate UV transmission across windows in electric vehicles (EV), hybrid vehicles (HV), and gas vehicles (GV) as well as variability based on year of manufacture and mileage to inform car manufacturers and consumers of the potential for UV exposure to the skin based on vehicle. To compare UV-A and UV-B transmission through EV, HV, and GV windows to evaluate differences in UV protection offered by various vehicle types. Comparative observational study that took place between June 10, 2024 and August 2, 2024. Outdoor setting with natural light exposure at car dealerships in Philadelphia, PA and New York, NY. 34 vehicles—15 gas vehicles (GV), 9 hybrid vehicles (HV), 10 electric vehicles (EV)—ranging from 2015 to 2025. Window status, with UV transmission measurements recorded with windows open and closed. UV-A and UV-B transmission through car windows was measured using UV transmission meters. The percent reduction in transmission was calculated. The front windshield and driver side window have statistically significant differences in UV-A attenuation across all vehicles with an average of 99.25% and 88.78% (p < 0.001), respectively. GV, HV, and EV all demonstrated significant differences in UV-A attenuation in most other vehicle windows compared to the front windshield. For GV, the front windshield, rear side windows (p = .176, p = .578) and back windshield (p = .457) blocked more UV-A than the front side windows. EV offered greater UV-A attenuation at the front and back windshield (p = .09) but not for any side windows, and HVs showed consistent differences in UV-A protection between the front windshield and all other windows. Domestic GV, trucks and luxury vehicles had no significant differences in UV-A attenuation across windows indicating reduced UV-A exposure for driver and passengers, whereas non-luxury vehicles had a notable difference in UV-A protection between the front windshield and all other windows. Regression analysis found mileage, not year of manufacture, to be a significant predictor of driver’s side UV-A attenuation, with more UV-A attenuation as vehicle mileage increases. Most vehicles evaluated offer effective UV-A and UV-B protection from the front windshield but lack sufficient UV-A protection for drivers nor consistently to other passengers with notable exceptions seen with domestic GV, trucks, and luxury vehicles. Mileage and not year of manufacture also contributed to additional UV-A attenuation. This underscores the importance of patient education on this known source for cumulative lifetime UV exposure and need for continued sun safety measures even while driving given potential UV-A impact on the skin.

Proteomic analysis of spinal dorsal horn in prior exercise protection against neuropathic pain

Neuropathic pain (NP) is a complex and prevalent chronic pain condition that affects millions of individuals worldwide. Previous studies have shown that prior exercise protects against NP caused by nerve injury. However, the underlying mechanisms of this protective effect remain to be uncovered. Therefore, the purpose of this study is to investigate how prior exercise affects protein expression in NP model rats and thus gain comprehensive insights into the molecular mechanisms involved. To achieve this objective, 6-week-old male Sprague–Dawley rats were randomly assigned into three groups, named as chronic constriction injury (CCI) of the sciatic nerve, CCI with prior 6-week swimming training (CCI_Ex), and sham operated (Sham). The CCI_Ex group underwent 6 weeks of swimming training before CCI surgery, while the CCI and sham groups had no intervention. Mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were used as the main observation indicators to evaluate the behavioral changes associated with pain. Tissues from the spinal dorsal horn of the rats in the three groups were collected at 4 weeks after operation. LC–MS/MS proteomic analysis based on the label-free approach was used to detect protein profiles, and volcano plots, Venn diagrams, and clustering heatmaps were used to identify differentially expressed proteins (DEPs). Gene Ontology (GO) annotations, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein–protein interaction networks were employed to explore the biological importance of DEPs. At 14, 21, and 28 days following CCI, CCI rats with prior exercise showed a significant increase in the MWT and TWL of the injured lateral hind paw compared with those without exercise. A total of 122 proteins with significant changes in abundance were detected after CCI surgery, and 55 proteins were detected in the comparison between the CCI_Ex and CCI groups. GO and KEGG enrichment analysis revealed that oxygen transport capacity and the complement and coagulation cascades may be the critical mechanism by which prior exercise protects against NP. Serpina1, DHX9, and Alb are the key proteins in this process and warrant further attention, as confirmed by the results of Western blot analysis. In conclusion, this study provides new evidence that active physical activity can accelerate the relief of hyperalgesia after NP. Proteomic analyses revealed the potential target proteins and pathways for this process, offering valuable data resources and new insights into the pathogenesis and therapeutic targets of NP.

D-mannose promotes diabetic wound healing through inhibiting advanced glycation end products formation in keratinocytes

BackgroundDiabetic chronic foot ulcers pose a significant therapeutic challenge around the world, resulting in adverse effects and complications in patients. D-mannose is enriched in cirtus peel and exerts beneficial effects among various diseases, especially against inflammation-related disorders.MethodsHere, we examined the potential effect of D-mannose during wound healing process in streptozotocin (STZ)-induced diabetes mice in vivo and by culturing keratinocytes under high glucose condition in vitro. The skin lesion healing was recorded in photos and evaluated by histochemical staining. What’s more, the advanced glycation end products (AGEs) concentration in blood and mice skin was quantified. Apoptotic cells were assessed by flow cytometry and Western blotting. Inflammatory cytokines and cellular differential gene expression levels were measured by real-time PCR. The expression of the AMPK/Nrf2/HO-1 signaling-related molecules was determined by Western blotting.ResultsWe first found that topical supplementation of D-mannose remarkably improved skin wound healing in diabetes mice. Furthermore, both in vivo and in vitro experiments demonstrated that D-mannose reduced the AGEs generation. Mechanistically, D-mannose inhibited AGEs, then upregulated AMPK/Nrf2/HO-1 signaling in the context of high glucose to maintain keratinocyte normal functions, which positively influenced macrophage and fibroblast to accelerate diabetic wound healing. Noteworthily, these protective effects of D-mannose were abolished by the pretreatment with inhibitors of AGEs or AMPK.ConclusionAs far as we know, this is the first study exploring the protective role of D-mannose on diabetic wound healing via topical supplementation. We find that D-mannose protects keratinocytes from high glucose stimulation via inhibition of AGEs formation as well as orchestrates inflammatory microenvironment in diabetic wounded skin, suggesting its supplementation as a potential therapy to promote refractory wound healing in diabetic patients.

Mucin Colocalizes with Influenza Virus and Preserves Infectivity in Deposited Model Respiratory Droplets.

The stability of influenza virus in respiratory particles varies with relative humidity (RH) and protein content. This study investigated the decay, or loss of infectivity, of influenza A virus (IAV) in 1-μL respiratory droplets deposited on a surface with varying concentrations of mucin, one of the most abundant proteins in respiratory mucus, and examined the localization of virions within droplets. IAV remained stable at 0.1% and 0.5% mucin in phosphate-buffered saline (PBS) over 4 h at 20%, 50%, and 80% RH, with a maximum decay of 1.2 log10/mL. In contrast, in pure PBS droplets, the virus decayed by at least 2.6 log10/mL after 4 h at 50% and 80% RH. Mucin's protective effect was independent of its concentration, except at 80% RH after 4 h. Confocal microscopy of the particles revealed that at 20% and 50% RH, mucin led to thicker coffee rings and dendritic patterns where virions colocalized with mucin. At 80% RH, no morphological difference was observed between PBS-only and mucin-containing droplets, but virions still colocalized with mucin in the center of droplets with 0.5% mucin. Analysis by digital droplet PCR showed that mucin helped maintain virus integrity. To our knowledge, this is the first study to localize influenza virus in model respiratory droplets. The results suggest that mucin's colocalization with virions in droplets may protect the virus from environmental stressors, enhancing its stability.

Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.

Natural flavonoids may be utilized as an important therapy for cardiovascular diseases (CVDs) caused by intestinal barrier damage. More research is being conducted on the protective properties of natural flavonoids against intestinal barrier injury, although the underlying processes remain unknown. Thus, the purpose of this article is to present current research on natural flavonoids to reduce the incidence of CVDs by protecting intestinal barrier injury, with a particular emphasis on intestinal epithelial barrier integrity (inhibiting oxidative stress, regulating inflammatory cytokine expression, and increasing tight junction protein expression). Furthermore, the mechanisms driving intestinal barrier injury development are briefly explored, as well as natural flavonoids having CVD-protective actions on the intestinal barrier. In addition, natural flavonoids with myocardial protective effects were docked with ZO-1 targets to find natural products with higher activity. These natural flavonoids can improve intestinal mechanical barrier function through anti-oxidant or anti-inflammatory mechanism, and then prevent the occurrence and development of CVDs.

Impact of particulate matter exposure on melanoma risk: A multicentre case-control study.

The relationship between particulate matter (PM) exposure and melanoma risk remains largely unexplored. This study aims to investigate the association between PM10 and PM2.5 long-term exposure and melanoma risk. Case-control study involving 2575 participants, comprising 1473 melanoma patients and 1102 healthy controls attending Departments of Dermatology of University Hospital in North and Central Italy. Demographic data, smoking status, history of sunburns and skin type were collected. PM10 and PM2.5 exposure levels were estimated for each participant's residential address using a Bayesian hierarchical model, providing daily concentrations at a 1 km2 spatial resolution from 2013 to 2021. Logistic regression analyses were performed to evaluate the association between PM exposure and melanoma risk, adjusting for potential confounders. Melanoma patients and controls were 52% males and had a mean age of 63.89 and 61.66 years, respectively. The majority of melanoma patients had Fitzpatrick phototypes 2 (59%) and 3 (36%). There were no significant differences in the geographical distribution of cases and controls based on ZIP codes (p = 0.894). The average melanoma Breslow thickness was 1.01 mm, with 68.15% of cases diagnosed at stage 0 and IA. The multivariate logistic regression revealed a protective effect for higher PM10 (OR = 0.89, 95%CI: 0.86-0.92, p < 0.001) and PM2.5 levels (OR = 0.72, 95%CI: 0.68-0.76, p < 0.001). Darker skin phototypes (Fitzpatrick 4) and cigarette smoking were also associated with a reduced risk of melanoma. Higher levels of PM10 and PM2.5 may have a protective effect against melanoma, potentially due to the reduction in ultraviolet radiation exposure. Further research to understand the complex interactions between environmental factors and melanoma risk are needed.

Nobiletin reduces 5-FU-induced lung injury with antioxidative, anti-inflammatory and anti-apoptotic activities.

Like other chemotherapeutic agents, 5-fluorouracil (5-FU) targets cancerous cells, but it also causes many unwanted side effects on healthy tissues and cells. Based on the undesirable effects of 5-FU, the aim of this study was to determine how 5-FU affects lung tissue and whether nobiletin has any protective effect. The study consisted of negative control, Nobiletin, 5-FU and Nobiletin + 5-FU groups. Nobiletin and Nobiletin + 5-FU groups received 10mg/kg Nobiletin i.g. for 7days. On day 8, 100mg/kg 5-FU was administered i.p. to 5-FU and Nobiletin + 5-FU groups. Biochemical and immunohistochemical analyses were performed on the lung tissues dissected at the end of the study. 5-FU caused growth retardation, disturbed the oxidant-antioxidant balance by increasing MDA levels and decreasing GSH levels, triggered cellular apoptosis by increasing Bax and caspase-3 levels and decreasing Bcl-2, also increased lung tissue inflammation and damage by increasing NFκB and IL-1β levels. However, it was determined that Nobiletin prevented the disruption of the oxidant-antioxidant balance, showed significant anti-apoptotic effects, especially by reducing Bax levels and partially modulating caspase-3 and Bcl-2 levels, and also exhibited anti-inflammatory effects by reducing NFκB and IL-1β levels and supported the normal development of animals. Our results showed that nobiletin pretreatment showed anti-inflammatory activity by inhibiting the NFκB pathway in 5-FU-induced lung injury, suppressed oxidative stress with its antioxidant activity and was effective in modulating cellular apoptosis with its anti-apoptotic activity. In conclusion, Nobiletin has been shown to have an important potential in reducing fluorouracil-induced tissue damage by acting through multiple pathways.

Anti-ferroptotic effects of natural polyphenols in nervous system injury: a narrative literature review.

Recent studies have shown that ferroptosis, a newly identified regulated cell death characterized by increased lipid peroxidation and accumulation of toxic lipid peroxides, is closely related to the pathophysiological processes of nervous system diseases which can be inhibited with iron chelators, lipophilic antioxidants, and lipid peroxidation inhibitors. To review the current evidence on the efficacy of various natural polyphenols in nervous system injury. The data selected for this review were collected by searching the MEDLINE/PubMed, Web of Science, Scopus, and Google Scholar database for articles published in English between 2000 and 2024 using the following terms: cell death, regulated cell death, ferroptosis, lipid peroxides, iron, and glutathione peroxidase. Natural polyphenols have been found to have some protective effects against nervous system disorders, which are attributed to a variety of biological properties, particularly antioxidant, immunomodulatory, and anti-inflammatory effects. The preclinical studies conducted on the use of the most common dietary polyphenols, including resveratrol, EGCG, curcumin, quercetin, gastrodin, baicalein & baicalin, carthamin, galangin, puerarin, morachalcone, and carnosic acid with the molecular mechanisms have been discussed. On the other hand, the results of a few clinical studies emphasize the primary role of iron in neuronal degeneration following some of nervous system injury. Some of the findings indicated that natural polyphenols as antioxidant supplements have anti-ferroptotic effects in nervous system disorders.

Reactivity of Olanzapine and Tricyclic Antidepressants on the Protective Effects of Trolox on Lipid Peroxidation Evaluated Using Fluorescence Anisotropy, Electron Paramagnetic Resonance Spectrometry, and Thermal Analysis.

Multiacting receptor-targeting antipsychotics and tricyclic antidepressants stimulate various neurotransmitter receptors despite the different targets of postsynaptic receptors and presynaptic reuptake transporters. Their auxiliary and adverse effects may be caused by multiple targets or the modification of the neuronal membrane. To evaluate the membrane responses to olanzapine, imipramine, desipramine, amitriptyline, lidocaine, and dibucaine, we examined the inhibition of lipid peroxidation in egg yolk phosphatidylcholine liposomes. By contrast, their effects on membrane fluidity were measured as the suppressive contributions of the inhibitory activity of Trolox on lipid oxidation. These drugs inhibit lipid peroxidation and exclude harmful reactive oxygen species and the protective effect of Trolox. The fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in saturated phospholipid liposome-containing drugs suggested that olanzapine, imipramine, and dibucaine enhanced membrane fluidity. The radical scavenging activity of 2,2-diphenylpicrylhidrazyl and galvinoxyl radicals was determined using electron paramagnetic resonance experiments, and their molecular flexibility was determined using thermograms for differential scanning calorimetry. Multiple regression analyses of the linear free energy relationship approach and comparative investigations revealed that the membranous fluidity of the liposomes, independent of the radical scavenging activity of the drugs, induced the inhibitory activity on lipid peroxidation. We discussed how these drugs act on nervous membranes and aimed to identify the relationship between uncertified functions and membranous fluidity.

Parthenolide improves sepsis-induced coagulopathy by inhibiting mitochondrial-mediated apoptosis in vascular endothelial cells through BRD4/BCL-xL pathway

BackgroundSepsis is a systemic inflammatory syndrome that can cause coagulation abnormalities, leading to damage in multiple organs. Vascular endothelial cells (VECs) are crucial in the development of sepsis-induced coagulopathy (SIC). The role of Parthenolide (PTL) in regulating SIC by protecting VECs remains unclear.MethodsThe study utilized septic rats and lipopolysaccharide (LPS)-stimulated VECs to simulate a SIC model and observe the therapeutic effects of PTL. Additionally, nanotechnology was employed to produce Nano-PTL (N-PTL), to observe whether it has advantages over PTL in treating SIC.ResultsPTL has been shown to mitigate lung injury in septic rats, significantly reduce tumor necrosis factor-α (TNF-α) levels, and increase survival rates. PTL treatment also enhances coagulation function, augments vascular endothelial cell (VEC) function, reduces mitochondrial fragmentation, and increases both mitochondrial oxygen consumption rate (OCR) and mitochondrial membrane potential (MMP), while inhibiting reactive oxygen species (ROS) production. By increasing BRD4/BCL-xL levels, PTL can prevent mitochondrial-mediated apoptosis in VECs, improve VEC function, and consequently ameliorate SIC. Additionally, nanotechnology-synthesized N-PTL further enhances the protective effects on VECs and coagulation function.ConclusionsThis study clarifies the therapeutic effects and mechanisms of PTL on SIC, offering new strategies and directions for the treatment of sepsis.

Nicotinamide Prevents The Plasticity Impairments And The Cognitive Dysfunction Caused By Bone Fracture In Older Mice.

Postoperative delirium (POD), an acute cognitive dysfunction linked to morbidity and mortality, is characterized by memory impairments and disturbances in consciousness, particularly in patients aged 65 and older. Neuroinflammation and NAD+ imbalance are key mechanisms behind POD, leading to synaptic and cognitive deterioration. However, how surgery contributes to POD and neuroinflammation remains unclear, and effective treatments are lacking. Here we used a rodent model of bone fracture to examine the impact of surgery on synaptic plasticity, inflammation, and cognition. Additionally, we explored whether treatment with Nicotinamide (NAM), a NAD+ precursor, reduced the neuroinflammation and metabolic imbalance caused by surgery. Female C57BL/6J mice aged 20-22 months underwent tibial fracture surgery and received pre- and post-surgery NAM treatment. Neuroinflammation, synaptic plasticity, and cognition were assessed 72 hours post-surgery via long-term potentiation (LTP) assays, dendritic spine counting, and behavioral tests (open field maze and Y-maze). Tibial fracture surgery decreased LTP, dendritic spine density, and hippocampal-dependent memory function, and increased hippocampal inflammatory markers (IL-1 beta mRNA, CD38, and SIRT1 protein content); NAM pretreatment prevented these changes. Given surgery adverse effects on LTP and dendritic spine density, we assessed cellular oxidative state and BDNF protein levels. We found that surgery increased the oxidation of ryanodine receptor calcium channels (cellular redox sensors), and decreased BDNF protein levels; NAM supplementation mitigated both effects and prevented the cognitive decline and synaptic plasticity deficits while reducing inflammation post-surgery by lowering IL-1 beta and CD38 protein levels. We propose that the CD38 signaling pathway mediates these NAM protective effects.

Investigating the Effect and Potential Mechanism of Rhamnetin 3-O-α-Rhamnoside on Acute Liver Injury In Vivo and In Vitro

Background/Objectives: Rhamnetin 3-O-α-rhamnoside (ARR) is a major flavonoid of the herb Loranthus tanakae Franch. &amp; Sav., which has been used for treating liver diseases in China. However, the protective effect of ARR on the liver has not been reported. Methods: Zebrafish larvae were used as a visual animal model, and liver injury was induced by thioacetamide (TAA) for an acute liver injury (ALI) model. The hepatoprotective activity of ARR was evaluated by assessing liver morphology, liver function indices, oxidative stress, and the mRNA expression levels of inflammation-related genes in the zebrafish model. Additionally, the ROS level, inflammatory factors, and protein expression related to the IKKβ/NF-κB signaling pathway were measured to investigate a potential mechanism of ARR in HepG2 cells. Results: ARR ameliorated TAA-induced growth retardation, reduced liver injury phenotypes, and decreased oxidative stress in the zebrafish. ARR was also able to lower ROS levels in HepG2 cells, effectively inhibit the overactivation of the IKKβ/NF-κB signaling pathway in pathological conditions, inhibit NF-κB p65 translocation from the cytoplasm to the nucleus, and reduce the release of intracellular inflammatory factors. Conclusions: ARR showed significant protective activity against TAA-induced liver injury in in vivo and in vitro models, and its potential mechanism was closely related to the IKKβ/NF-κB signaling pathway.

Weekly administration of betulinic acid prevents development of chronic renal failure from acute renal failure in folic acid-induced mouse model of kidney injury.

Betulinic acid (BA) has been shown to exhibit various pharmacological activities and it has shown the protective effect on acute renal failure (ARF) and chronic renal failure (CRF); however, no reports are available on its effect on ARF-CRF transition. Therefore, we aimed to investigate the effects of BA on ARF-CRF transition. A single dose of250 mg/kg body weight (BW) intraperitoneal injection of folic acid was given in mice for inducing ARF-CRF transition (injury group; I) on day 1. Further, excess of these mice received BA at 30 mg/kg BW dose for 3 days (on days 1, 2, 3) in one group (IT3) and for 7 days (on days 1, 2, 3, 7, 14, 21, 28) in another group (IT7). All mice were sacrificed on day 28. Mice in injury group (I) showed elevated serum creatinine along with oxidative stress markers like urine nitrite, tissue lipid peroxidation, nitrotyrosine and fibrotic markers such as tissue α-smooth muscle actin and matrix metalloproteinase-2 activity. They had attenuated levels of urine creatinine and tissue reparative cytokines viz. interleukin-4 and interleukin-13. Excess of fibroblasts and extracellular matrix in the interstitia and periglomerular area in microscopy further support these findings. Seven days of BA treatment regimen (IT7) significantly improved serum and urine parameters accompanied by reduced oxidative stress, improved reparative cytokines and lesser maladaptive matrix deposition. The above findings reveal that weekly BA treatment regimen has potential to prevent development of CRF after ARF.

Characterization of diabetic kidney disease in 235 patients: clinical and pathological insights with or without concurrent non-diabetic kidney disease

BackgroundThis study aimed to explore the clinical and pathological features of patients with diabetic kidney disease (DKD), with and without non-diabetic kidney disease (NDKD), through a retrospective analysis. The objective was to provide clinical insights for accurate identification.MethodsA retrospective analysis of 235 patients admitted to the Department of Nephrology at Hangzhou Hospital of Traditional Chinese Medicine was conducted between July 2014 and December 2022. These patients underwent renal biopsy and received a pathology-based diagnosis of DKD. They were categorized into the DKD alone group (93 cases) and the DKD + NDKD group (142 cases).ResultsIn the DKD alone group, gender distribution was even, with ages mainly between 50 and 59 years, and a disease duration of less than 5 years, primarily presenting nodular diabetic glomerulosclerosis. In contrast, the DKD + NDKD group had a higher male incidence, a wider age range, longer disease duration, and prevalent diffuse diabetic glomerulosclerosis. Acute and chronic tubulointerstitial lesions and IgA nephropathy were the predominant types of combined NDKD, accounting for 40.14% and 35.21%, respectively. Clinical correlation analysis revealed associations between glomerular grading, tubulointerstitial lesions, renal arteriolar vitelliform lesions, renal vascular atherosclerosis, and clinical parameters such as 24-hour urine protein, hemoglobin, and urinary specific gravity. Multifactorial logistic regression analysis identified independent factors affecting DKD + NDKD, including body mass index, blood creatinine level, microscopic erythrocyte grade, urinary immunoglobulin G/creatinine ratio, and serum immunoglobulin A.ConclusionThe research underscores distinctions in age, gender distribution, disease duration, and renal pathology between DKD alone and DKD + NDKD groups. Additionally, significant discriminative factors including BMI, blood creatinine level, microscopic erythrocyte grade, UIgG/urine creatinine ratio, and serum IgA levels help differentiate DKD from NDKD, thereby enabling personalized treatment approaches. Furthermore, the study highlights the role of RASi as the most commonly used drug in the treatment of both DKD and NDKD, with emerging drugs such as SGLT2 inhibitors showing promising renal protective effects.

Lipids, lipid-lowering drug target genes and pancreatic cancer: a Mendelian randomization study.

Pancreatic cancer (PC) is a malignant tumor with a low survival rate. Lipid modifiers show potential for PC therapy, but evidence is lacking. This Mendelian randomization (MR) study aimed to explore the relationship between lipid traits, and lipid-lowering drug target genes with PC risk. Genetic instrumental variables associated with lipid traits and lipid-lowering drug target genes were used to perform MR analyses of PC risk. MR estimation was based on genome-wide association study data from two large sample sets, and the MR results were meta-analyzed to assess their impact on PC risk. To ensure the reliability of lipid-modifying drug targets, we conducted a Summary Data-based Mendelian Randomization (SMR) analysis. Additionally, a two-step MR analysis was employed to explore potential mediating effects. In two independent datasets, HMG-CoA reductase (HMGCR) inhibition was statistically associated with a lower risk of PC (OR 0.50, [95% CI 0.25-1.00]; p = 0.0453). The results were further supported by SMR analysis, which showed a similar association (OR 0.51, [95% CI 0.28-0.96]; p = 0.0369). Mediation analysis revealed that 11.69% of the protective effect of HMGCR inhibitors on PC is mediated through lower BMI levels. No significant effect of lipid traits and the other eight lipid-lowering drug targets on PC risk was found. This study suggests that HMGCR may be a potential drug target for the treatment or prevention of PC, providing important insights into the use of lipid-targeted drugs in PC therapy.