Releasing Hormone Research Articles

Another fly diuretic hormone: tachykinins increase fluid and ion transport by adult Drosophila melanogaster Malpighian 'renal' tubules.

Insects such as the model organism Drosophila melanogaster must modulate their internal physiology to withstand changes in temperature and availability of water and food. Regulation of the excretory system by peptidergic hormones is one mechanism by which insects maintain their internal homeostasis. Tachykinins are a family of neuropeptides that have been shown to stimulate fluid secretion from the Malpighian 'renal' tubules (MTs) in some insect species, but it is unclear if that is the case in the fruit fly, D. melanogaster. A central objective of the current study was to examine the physiological role of tachykinin signaling in the MTs of adult D. melanogaster. Using the genetic toolbox available in this model organism along with in vitro and whole-animal bioassays, our results indicate that Drosophila tachykinins (DTKs) function as diuretic hormones by binding to the DTK receptor (DTKR) localized in stellate cells of the MTs. Specifically, DTK activates cation and anion transport across the stimulated MTs, which impairs their survival in response to desiccation because of their inability to conserve water. Thus, besides their previously described roles in neuromodulation of pathways controlling locomotion and food search, olfactory processing, aggression, lipid metabolism and metabolic stress, processing of noxious stimuli and hormone release, DTKs also appear to function as bona fide endocrine factors regulating the excretory system and appear essential for the maintenance of hydromineral balance.

LITERATURE REVIEW THE ROLE OF ACUPUNCTURE IN THE MANAGEMENT OF PERIPHERAL NEUROPATHY

Peripheral neuropathy (PN) is a condition characterized by damage to the peripheral nervous system, resulting in symptoms such as pain, numbness, and weakness in the hands and feet. The most common causes include diabetes, thyroid disorders, vitamin B12 deficiency, alcohol abuse, chemotherapy, and human immunodeficiency virus (HIV) infection. Despite the availability of various treatments, neurological disorders remain a significant therapeutic challenge. The therapeutic effects of acupuncture are attributed to several mechanisms, including stimulation of nerve fibers, restoration of blood flow, release of neurotransmitters and hormones, modulation of the autonomic nervous system, anti-inflammatory effects, and increased neuroplasticity. These mechanisms collectively contribute to the relief of symptoms associated with peripheral neuropathy. Evidence suggests that acupuncture is beneficial in treating peripheral neuropathy. Studies have shown that acupuncture can improve nerve conduction study parameters in sensory and motor nerves, reduce neuropathic pain, and improve overall nerve function. Certain acupuncture points such as ST-36, GB-34, SP-3, SP-8, and BI-56 have been identified as particularly effective in managing symptoms of peripheral neuropathy. Although more rigorous studies are needed to fully characterize the effects of acupuncture on peripheral neuropathy, the available evidence supports its use as a complementary therapy. Standardized acupuncture protocols that combine anatomical correlation with peripheral nerves and traditional approaches to neuropathic pain management appear to be effective. Further studies with larger sample sizes and randomized comparisons to sham acupuncture will help establish acupuncture as a guideline for treating peripheral neuropathy. This review outlines the potential of acupuncture as a complementary therapy in the management of peripheral neuropathy.

Exenatide-Modified Deferoxamine-Based Nanoparticles Ameliorates Neurological Deficits in Parkinson's Disease Mice.

To avoid the biotoxicity and poor bioavailability of deferoxamine mesylate (DFO), an iron chelation for the treatment of Parkinson's disease (PD), a self-oriented DFO nanoparticle functionalized with Exendin-4 was developed, which can be targeted delivered into the lesion brain area to achieve synergistic effects against PD by iron chelation and inflammatory suppression. The self-oriented DFO nanoparticles (Ex-4@DFO NPs) were synthesized by double emulsion technique, and characterized in terms of the particle size, morphology and DFO encapsulation efficiency. The cellular internalization, biocompatibility and cytoprotection of NPs were assessed on BV-2 and SH-SY5Y cells. The brain targeting and therapeutic effect of NPs were investigated in MPTP-induced PD mice by near-infrared II fluorescence imaging and immunofluorescence staining, as well as mobility behavioral tests. Ex-4@DFO NPs with a particle size of about 100 nm, showed great biocompatibility and cytoprotection in vitro, which inhibited the decrease of mitochondrial membrane potential of SH-SY5Y cells and the release of inflammatory factors of BV-2 cells. In MPTP-induced PD mice, Ex-4@DFO NPs could penetrate the BBB into brain, and significantly mitigate the loss of dopaminergic neurons and inflammation in the substantia nigra, finally alleviate the mobility deficits. This self-oriented nanosystem not only improved the biocompatibility of DFO, but also enhanced therapeutic effects synergistically by ameliorating neuronal damage and neuroinflammation, showing a potential therapeutic strategy for PD.

Lactiplantibacillus plantarum SG5 inhibits neuroinflammation in MPTP-induced PD mice through GLP-1/PGC-1α pathway

Mounting evidence suggests that alterations in gut microbial composition play an active role in the pathogenesis of Parkinson's disease (PD). Probiotics are believed to modulate gut microbiota, potentially influencing PD development through the microbiota-gut-brain axis. However, the potential beneficial effects of Lactiplantibacillus plantarum SG5 (formerly known as Lactobacillus plantarum, abbreviated as L. plantarum) on PD and its underlying mechanisms remain unclear. In this study, we employed immunofluorescence, Western blotting, ELISA, and 16S rRNA gene sequencing to investigate the neuroprotective effects of L. plantarum SG5 against neuroinflammation in an MPTP-induced PD model and to explore the underlying mechanisms. Our results demonstrated that L. plantarum SG5 ameliorated MPTP-induced motor deficits, dopaminergic neuron loss, and elevated α-synuclein protein levels. Furthermore, SG5 inhibited MPTP-triggered overactivation of microglia and astrocytes in the substantia nigra (SN), attenuated disruption of both blood-brain and intestinal barriers, and suppressed the release of inflammatory factors in the colon and SN. Notably, SG5 modulated the composition and structure of the gut microbiota in mice. The MPTP-induced decrease in colonic GLP-1 secretion was reversed by SG5 treatment, accompanied by increased expression of GLP-1R and PGC-1α in the SN. Importantly, the GLP-1R antagonist Exendin 9–39 and PGC-1α inhibitor SR18292 attenuated the protective effects of SG5 in PD mice. In conclusion, we demonstrate a neuroprotective role of L. plantarum SG5 in the MPTP-induced PD mouse model, which likely involves modulation of the gut microbiota and, significantly, the GLP-1/PGC-1α signaling pathway.

3D nanofiber sponge based on natural insect quaternized chitosan/pullulan/citric acid for accelerating wound healing

Extensive traumatic injuries and difficult-to-heal wounds, induced by many circumstances, impose a significant social and economic burden on an annual basis. Thus, innovative wound dressings that encourage wound healing are greatly needed. In this work, we prepared a novel insect chitosan (MCS) using waste pupal shells from housefly (Musca domestica L.) culture. After conducting comparative investigations with commercially available chitosan, it was shown that MCS exhibited comparable qualities and may be used as a substitute source of commercial chitosan. A quaternized chitosan/pullulan/citric acid three-dimensional nanofiber sponge (3D-NS) of natural origin was prepared by electrostatic spinning and gas foaming techniques after MCS was quaternized. In vitro, tests showed that the 3D-NS had a higher liquid absorption capacity than the two-dimensional nanofibrous membrane (2D-NM). Additionally, the 3D-NS showed improved hemostatic, pro-cell proliferation, antibacterial, and anti-inflammatory qualities. In vitro, tests demonstrated that 3D-NS could inhibit the release of inflammatory factors, promote angiogenesis, accelerate collagen deposition, and promote wound contraction. These effects considerably facilitated the healing process of wounds in rats with full-thickness skin damage. In conclusion, the great bioactivity and physicochemical properties of 3D-NS render it an optimal candidate for developing novel wound dressings.

Characterization of Age-Dependent Changes in Skeletal Muscle Repair and Regeneration Using a Mouse Model of Acute Muscle Injury.

Acute skeletal muscle injury initiates a process of necrosis, debris clearance, and ultimately tissue regeneration via myogenesis. While skeletal muscle stem cells (MuSCs) are responsible for populating the proliferative myogenic progenitor pool to fuel muscle repair, recruited and resident immune cells have a central role in the regulation of muscle regeneration via the execution of phagocytosis and release of soluble factors that act directly on MuSCs to regulate myogenic differentiation. Therefore, the timing of MuSC proliferation and differentiation is closely linked to the populations and behaviors of immune cells present within skeletal muscle. This has important implications for aging andmuscle repair, as systemic changes in immune system function contribute to a decline in muscle regenerative capacity. Here, we present adapted protocols for the isolation of mononuclear cells from skeletal muscles for the quantification of immune cell populations using flow cytometry. We also describe a cardiotoxin skeletal muscle injury protocol and detail the expected outcomes including immune cell infiltration to the injured sites and formation of new myocytes. As immune cell function is substantially influenced by aging, we extend these approaches and outcomes to aged mice.

Exudate Unidirectional Pump to Promote Glucose Catabolism Triggering Fenton-Like Reaction for Chronic Diabetic Wounds Therapy.

The massive accumulation of exudate containing high concentrations of glucose causes wound infection and triggers the release of inflammatory factors, which in turn delays the closure of diabetic wounds. In this study, a Janus membrane is constructed by combining glucose oxidase (GOx) and copper ions (Cu2+) for the treatment of diabetic wounds, which is named as Janus@GOx/Cu2+. It consists of hydrophobic, transitional, and superhydrophilic layers in a three-layer structure with gradient hydrophilicity for self-pumping properties. The Janus@GOx/Cu2+ membrane triggers a series of cascading reactions while pumping out diabetic wound exudates. First, glucose oxidase loaded onto the hydrophilic layer of the Janus@GOx/Cu2+ membrane decomposes glucose into hydrogen peroxide (H2O2) and glucuronic acid, reducing the local glucose level. The generated glucuronic acid neutralizes the local alkaline environment of chronic wounds. Simultaneously, the H2O2 interacts with the Cu2+ contained in the hydrophobic layers of the Janus@GOx/Cu2+ membrane via a Fenton-like reaction, generating hydroxyl radicals with excellent bactericidal properties. Cu2+ promotes angiogenesis and wound healing in diabetic wounds. Under the action of multiple responses, the Janus@GOx/Cu2+ membrane promotes wound healing in diabetic infections.

3D-printed biomimetic bone scaffold loaded with lyophilized concentrated growth factors promotes bone defect repair by regulation the VEGFR2/PI3K/AKT signaling pathway

This study investigates the effects of concentrated growth factors (CGF) and bone substitutes on the proliferation and differentiation of bone marrow mesenchymal stem cells (BMSCs), as well as the development of a novel 3D-printed biomimetic bone scaffold. Based on the structure of cancellous bone, 3D-printed bionic bone with sustainable release of growth factors and Ca2+ was prepared. Using BMSCs and EA.hy926 in co-culture with the bionic bone scaffold, experimental results demonstrate that this bionic structural design enhances cell proliferation and adhesion, and that the bionic bone possesses the ability to promote bone and vascular regeneration directly. Transcriptomics, western blot analysis, and flow cytometry are employed to investigate the effects of CGF and Ca2+ on the signaling pathways of BMSCs. The study reports that vascular endothelial growth factor (VEGF) released by CGF activated VEGFR2 on BMSCs, leading to Ca2+ influx and activation of the PI3K/AKT signaling pathway, thereby influencing osteogenesis. Animal experiments confirm the ability of the bionic bone to promote osteogenesis in vivo, and its unique degradation pattern accelerates the in vivo repair of bone defects. In conclusion, this study presents a novel biomimetic strategy and, for the first time, explores the potential mechanism by which VEGF and Ca2+ regulate BMSCs differentiation through the VEGFR2/PI3K/AKT signaling pathway. These insights offer a new perspective for the development of innovative bone substitute materials.

Didang decoction attenuates cancer-associated thrombosis by inhibiting PAD4-dependent NET formation in lung cancer.

This research aims to investigate the impact of Didang decoction (DD) on the formation of neutrophil extracellular traps (NETs) and cancer-associated thrombosis in lung cancer. BALB/c nude mice were used to establish xenograft models for inducing deep vein thrombosis. Tumor growth and thrombus length were assessed. The impact of DD on NET generation was analyzed using enzyme-linked immunosorbent assay, immunofluorescence staining, quantitative real-time PCR, and western blot analysis, both in vivo and in vitro. CI-amidine, a PAD4 inhibitor, was employed to evaluate the role of PAD4 in the generation of NETs. In vivo studies demonstrated that treatment with DD reduced tumor growth, inhibited thrombus formation, and decreased the levels of NET markers in the serum, tumor tissues, neutrophils, and thrombus tissues of mice. Additional data indicated that DD could suppress neutrophil counts, the release of tissue factor (TF), and the activation of thrombin-activated platelets, all of which contributed to increased formation of NETs in mouse models. In vitro, following incubation with conditioned medium (CM) derived from Lewis lung carcinoma cells, the expression of NET markers in neutrophils was significantly elevated, and an extracellular fibrous network structure was observed. Nevertheless, these NET-associated changes were partially counteracted by DD. Additionally, CI-amidine reduced the expression of NET markers in CM-treated neutrophils, consistent with the effects of DD. Collectively, DD inhibits cancer-associated thrombosis in lung cancer by decreasing PAD4-dependent NET formation through the regulation of TF-mediated thrombin-platelet activation. This presents a promising therapeutic strategy for preventing and treating venous thromboembolism in lung cancer.

Clinical significance and underlying mechanism of long non-coding RNA SNHG12 in lower extremity deep venous thrombosis.

D-dimer is widely used in the diagnosis of deep vein thrombosis (DVT), but the specificity is low. The study examined the diagnostic value of long non-coding RNA (lncRNA) SNHG12 in DVT, and preliminarily discussed its mechanism. SNHG12 levels were detected in 200 elderly fracture patients via RT-qPCR, including 38 DVTs. Logistic regression analysis and receiver operating characteristic (ROC) curve were applied for diagnostic value evaluation. HUVECs were used for function study. Cell proliferation, migration, apoptosis, release of inflammatory cytokines, and adhesion factors were detected. Student's t test and one-way ANOVA were applied for data comparison between two or among three or more groups. Correlation analysis of indicators was completed via Pearson's correlation analysis. Bioinformatics analysis predicted the target miRNAs and genes of SNHG12, with GO and KEGG for the function enrichment. It was found that SNHG12 was at low expression in DVT patients, and negatively correlated with D-dimer concentration (r = -0.535). SNHG12 and D-dimer were independent influence factors related to the development of DVT. SNHG12 and D-dimer combination had the best performance in DVT diagnosis. In HUVECs, SNHG12 promoted cell proliferation and migration and restricted the release of inflammatory cytokines and adhesion factors, but these influences were counteracted by miR-424-5p. A total of 208 overlapping target genes of miR-424-5p were identified, and their function was enriched in cellular cycle and senescence. PI3K-Akt signaling pathway was the most significant pathway based on KEGG results. In conclusion, SNHG12 had good diagnostic potential for DVT combined with D-dimer. SNHG12 maintains vascular endothelial cell function by acting as a competitive endogenous RNA (ceRNA) for miR-424-5p.

Dynamic polysaccharide/platelet-rich plasma hydrogels with synergistic antibacterial activities for accelerating infected wound healing

Platelet-rich plasma (PRP) has been recognized as an effective therapy in regenerative medicine and surgery, which can reduce the risk of antibiotic abuse and promote the healing of infected wounds. Recent advances in PRP-based treatments have focused on the controlled release of growth factors in PRP with biocompatible hydrogels and antimicrobial promotion by introducing hydrogel components or antibiotics, while the inherent antimicrobial activity of PRP is mostly neglected or sacrificed. Here, we demonstrate the combination of an antimicrobial polysaccharide, carboxymethyl chitosan, and PRP to construct an antimicrobial hydrogel via dynamic bonding with oxidized chondroitin sulfate. Significant inhibitory effects against Staphylococcus aureus and Escherichia coli (95 % of inhibition rate) are achieved through the synergistic contributions of the polysaccharide and PRP. Additionally, the resulting hydrogel promotes the migration of NIH-3T3 fibroblasts and collagen deposition by approximately 1.7 and 1.8 times, respectively, thereby accelerating the healing process of infected wounds. This work may bring new perspectives for potent applications of PRP-based hydrogel dressings for antibiotic-free management of infected wounds.

Network-based pharmacology and experimental validation to explore the mechanism of action of the Jiawei Pentongling formula for the treatment of endometriosis-related pain.

To investigate the effects and mechanisms of the Jiawei Pentongling formula (, JWPTL) in treating endometriosis-related pain using network pharmacology study and experimental validation. Active ingredients and relevant targets of JWPTL, as well as genes for endometriosis-related pain, were collected from public databases. Prediction of core targets and pathways of JWPTL against pain associated with endometriosis by protein-protein interaction (PPI) network work, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis. The Sprague-Dawley rat endo-metriosis model was constructed using the autologous endosomal transplantation method, and the successfully modeled rats were randomly divided into the model group and the JWPTL group, with 8 rats in each group. Another 8 rats were set up in the sham group. Rats in the JWPTL group used the rectal delivery method with the addition of JWPTL (7.77 g·kg-1·d-1) once a day for 28 d. Rats in the model and sham-operated groups were given equal amounts of saline using the same administration method. The 50% paw withdrawal threshold (PWT) of the rats was measured at different time points. After the intervention, the expression of phosphatidylinositol 3-kinase (PI3K) and protein kinase B (Akt) proteins and mRNA in endometriotic tissues was detected by immune-ohistochemistry and reverse transcription-polymerase chain reaction. From GeneCards, Online Mendelian Inheritance in Man and other databases, a total of 964 endometriosis (EMs) -related pain targets were screened, 142 active ingredients of JWPTL, 605 targets, and 221 potential targets were obtained by intersection of Venn diagram; 44 core targets were identified by constructing PPI network. KEGG enrichment analysis showed that JWPTL mainly involves the PI3K-Akt signaling pathway, estrogen signaling pathway, hypoxia inducible factor-1 signaling pathway, tumour necrotizing factor signaling pathway, and other signaling pathways in the treatment of EMs-related pain. Animal experiments showed that JWPTL could up-regulate the mechanical pain threshold and reduce the expression of PI3K and Akt proteins and mRNA in ectopic endometrial tissues of model rats. The present study preliminarily analyzed the pharmacological mechanism of the formula, and molecular docking and animal experiments showed the feasibility of this study, suggesting that the formula may inhibit the release of inflammatory factors and reverse the pain associated with EMs by downregulating the PI3K/Akt signaling pathway.

Overview of mechanism of electroacupuncture pretreatment for prevention and treatment of cardiovascular and cerebrovascular diseases.

Cardio-cerebrovascular disease (CCVD) is a serious threat to huma strategy to prevent the occurrence and development of disease by giving electroacupuncture intervention before the disease occurs. EAP has been shown in many preclinical studies to relieve ischemic symptoms and improve damage from ischemia-reperfusion, with no comprehensive review of its mechanisms in cardiovascular disease yet. In this paper, we first systematically discussed the meridian and acupoint selection law of EAP for CCVD and focused on the progress of the mechanism of action of EAP for the prevention and treatment of CCVD. As a result, in preclinical studies, AMI and MCAO models are commonly used to simulate ischemic injury in CCVD, while MIRI and CI/RI models are used to simulate reperfusion injury caused by blood flow recovery after focal tissue ischemia. According to the meridian matching rules of EAP for CCVD, PC6 in the pericardial meridian is the most commonly used acupoint in cardiovascular diseases, while GV20 in the Du meridian is the most commonly used acupoint in cerebrovascular diseases. In terms of intervention parameters, EAP intervention generally lasts for 30 min, with acupuncture depths mostly between 1.5 and 5 mm, stimulation intensities mostly at 1 mA, and commonly used frequencies being low frequencies. In terms of molecular mechanisms, the key pathways of EAP in preventing and treating cardiovascular and cerebrovascular diseases are partially similar. EAP can play a protective role in cardiovascular and cerebrovascular diseases by promoting autophagy, regulating Ca2+ overload, and promoting vascular regeneration through anti-inflammatory reactions, antioxidant stress, and anti-apoptosis. Of course, both pathways involved have their corresponding specificities. When using EAP to prevent and treat cardiovascular diseases, it involves the metabolic pathway of glutamate, while when using EAP to prevent and treat cerebrovascular diseases, it involves the homeostasis of the blood-brain barrier and the release of neurotransmitters and nutritional factors. I hope these data can provide experimental basis and reference for the clinical promotion and application of EAP in CCVD treatment.

Chronic PPARα/γ and CB2R agonist treatments attenuated visceral adipose tissue (VAT)-derived extracellular vesicle-related VAT and intestinal abnormalities in NASH mice

This study explores the mechanisms and combined effects of chronic peroxisome proliferator-activated receptor (PPAR)α/γ and cannabinoid receptor 2 (CB2R) agonists on visceral adipose tissue (VAT)-derived extracellular vesicle (EVs) release and associated systemic/VAT inflammation, decreased VAT capillary density/fibrosis, and intestinal inflammation/hyperpermeability in nonalcoholic steatohepatitis (NASH) mice. NASH mice receiving 1 month of PPARα/γ agonist aleglitazar (10 mg/kg/day), CB2R agonist JWH015 (3 mg/kg/day) alone or combined. High EV release from VAT of NASH mice was associated with severe systemic/VAT/intestinal inflammation, reduced capillary network of VAT, and intestinal hyperpermeability. Combined JWH015 with aleglitazar treatment significantly suppressed HFD-induced obesity/adiposity, inhibited VAT expansion, reduced VAT inflammation/fibrosis, normalized VAT capillary network, and attenuated intestinal mucosal injury, inflammation, and hyperpermeability in NASH+aleg+JWH015 mice. The inhibition of AT-derived EV release and hypoxia inducible factor (HIF)1α levels in AT-derived EV, normalization of CB2R, PPARα, PPARγ, PPARγ1, PPARγ2, tight junction proteins, VEGF/CD31 expression, and downregulations of HIF1α, MCP-1 and TGFβ1 were observed in the VAT and intestine of the NASH+aleg+jwh015 group. In vitro experiments revealed that PPARα/γ and CB2R activation attenuated NASH AT-derived EV (EVnash)-induced pathogenic changes in the J774/SVEC4-10/Caco2 /3T3-L1 cell system. This study suggested that VAT-derived EVs contribute to the pathogenesis of NAFLD and that combined PPARα/γ and CB2R agonist treatment reduces VAT-released EV release and HIF1/MCP-1 signals to ameliorate hepatic steatosis and VAT/intestine abnormalities of NASH mice.

Crack arrest characteristics and dynamic fracture parameters of moving cracks encountering double holes under impact loads

Brittle materials such as rock or concrete contain a large number of micro-cracks, voids, and other defects. Under external impacting loads, the interaction between fissures and holes affects the bearing capacity and stability of Engineering structures. To study the interaction mechanism between moving cracks and circular holes, A large-size semi-circular notched with a fissure and double circular hole (SNFDH) specimen was suggested in this research, and the dynamic fracture tests were carried out on the SNFDH specimens with different double circular hole spacing (35mm, 40 mm, 45 mm, 50 mm, 55 mm, 60 mm, and 70 mm) using a drop hammer impact test device. Crack propagation gauges were employed to track the time and velocity at which the crack propagated along its trajectory. Dynamic Drucker-Prager yield criterion and the cumulative damage failure criterion were used in the numerical simulation of SNFDH concrete materials. The program AUTODYN was employed to simulate the crack growth characteristics when a crack encounters the double hole. The program ABAQUS was applied to calculate the dynamic fracture parameter of cracks. The test results manifest that the crack propagating trajectory has three different characteristics according to the double hole spacing; the double circular hole has an arresting function for a moving crack; the size of the double hole spacing has a significant effect on the crack propagating velocity, crack propagating length, dynamic stress intensity factor and dynamic energy release rate; the configuration of the SNFDH specimen can be used to investigate the crack arrest mechanism when moving crack encountering double holes.

Exploring a novel toxicological mechanism: Ammonia-N induces neurotoxicity, oxidative damage in brain tissue, and modulates the expression of central appetite factors to suppress feeding in juvenile Siberian sturgeon (Acipenser baerii Brandt)

Ammonia-N is a common toxic factor in aquatic environment, known to inhibit fish feeding, yet its mechanism remains unclear. To investigate the toxicological mechanism of ammonia-N in inhibiting fish feeding, this study conducted experiments exposing juvenile Siberian sturgeon (Acipenser baerii) to ammonia-N at concentrations of 0, 5, 10, and 15 mg/L for 14 days. The results revealed a significant reduction in both daily and cumulative food intake. Obviously decreased condition factor (CF), hepatosomatic index (HSI), and viscerosomatic index (VSI) at 15 mg/L (P < 0.05). Besides, the serum ammonia concentration significantly increased on the 14th day, while the neurotoxic marker acetylcholinesterase (AchE) showed a consistent increase over the 14-day period (P < 0.05). Pathological examination of brain tissue demonstrated that ammonia-N induced damage, particularly evident in 15 mg/L ammonia-N group, where severe nerve fiber dissolution was observed. Moreover, the activity of superoxide dismutase (SOD) was significantly increased in the brain on the 1st, 3rd, and 7th day (P < 0.05). RNA-seq analysis o revealed 1566, 2188, and 2026 differentially expressed genes (DEGs) were obtained in the 5, 10, and 15 mg/L ammonia-N groups, respectively, compared to the control group, and 30 DEGs related to appetite regulation were identified. Further quantitative real-time PCR (qPCR) analysis indicated that ammonia-N exposure changed the expressions of appetite factors, including downregulation of agouti-related protein (agrp) and neuropeptide Y (npy), and upregulation of pro-opiomelanocortin (pomc), cocaine-and amphetamine-regulated transcript peptide (cart), and corticotropin releasing factor (crf) (P < 0.05). Therefore, these results suggest that ammonia-N inhibits feeding via neurotoxicity induced oxidative damage which primarily by downregulating appetite promoting factors and upregulating appetite-inhibiting factors. This study lays the groundwork for deeper understanding of the toxicological mechanism of ammonia-N on aquatic animals, particularly its detrimental effects on fish brain function and feeding behavior.

Clinical Efficacy and Safety of Low-Energy Extracorporeal Shock Wave Therapy for Various Conditions of Deep Dermal and Subdermal Fibrosis.

Extracorporeal shock wave therapy (ESWT) enhances extracellular matrix remodeling and tissue regeneration by promoting growth factor release, regulating blood and lymphatic flows, and reducing fat and fibrotic tissues. Focused shock wave therapy (F-SWT), radial shock wave therapy (R-SWT), and combined F-SWT and R-SWT have been used to deliver different patterns of shock energy depending on the characteristics of the target lesions. We investigated the efficacy and safety of ESWT in patients with dermal and subdermal fibrosis. Fifty-two patients treated with F-SWT and/or R-SWT for dermal and subdermal fibrosis caused due to various reasons were retrospectively analyzed by reviewing their medical records, clinical images, and ultrasound study images. The mean number of pulses administered for F-SWT on the cheek, temple, and chin were 2600.0 ± 1040.8 shocks/session and for R-SWT were 5080.0 ± 2234.6 pulses/session, and the number of treatment sessions were 8.0 ± 4.4. In patients who were treated with ESWT on the abdomen, the mean number of pulses for F-SWT were 2600.0 ± 2408.3 shocks/session and for R-SWT were 8400.0 ± 894.4 pulses/session, and the number of treatment sessions were 3.2 ± 1.6. Most patients were satisfied with the results. Pain during ESWT was well tolerated and post-ESWT edema was more common in R-SWT than in F-SWT. Our data demonstrated that ESWT effectively and safely improved the clinical appearance and functional movement of patients with dermal and subdermal fibrosis caused due to various reasons.

Investigation of the Effect of Nano-melatonin on Oxidative Stress in Sera of Patients with Polycystic Syndrome

Background: The association between polycystic ovary syndrome (PCOS) and oxidative stress in women, the possible causes of PCOS, insulin resistance (IR), obesity, and oxidative stress. Oxidants are chemical elements that tend to gain electrons, losing positive charge. The Oxidative Stress (OS) is defined as an imbalance between the formation and synthesis of free radicals and the antioxidant defense system, which results in oxidative damage. Objective: The purpose of this research is to investigate the effect of nano-melatonin on oxidative stress in the sera of patients with polycystic syndrome. Methods: The study includes 120 Iraqi women, divided into two groups: 60 PCOS patients and 60 healthy control patients. Sample Analysis Biochemistry analyses the hormonal profile and determines the hormonal levels (LH, FSH, Testosterone, and Prolactin) that were identified for all controls and patients. Hormones analysis was performed using the enzyme-linked fluorescent assay (ELFA) technique. Synthesized ML nanoparticles by ultrasonic sonication. Results: The results indicate that the mean of serum LH significantly increased (P&lt;0.02) in PCOS BMI ≥ 25 patients G1 (6.19±3.13) mIU/mL compared with controls C1 (4.504±1.591) mIU/mL, while a nonsignificant difference (P&gt;0.05) when compared the BMI&lt;25 kg/m2 for G2 (5.55±1.93) with control group C2 (6.31±2.58) of luteinizing hormone in G1 and G2. Conclusions: An increased ratio of LH to FSH was shown to be characteristic of PCOS. For PCOS, high LH values are crucial. For the purpose of diagnosing PCOS, high LH values are crucial release of gonadotropin hormones (LH, FSH) from the pituitary. To higher the production of androgen in ovarian theca cells, The LH receptor is activated by the luteinizing hormone (LH). The nano Mel was higher in the inhibition of Oxidative stress two causes nano-melatonin high surface area and small size.

Knockout of neutrophil cytosolic factor 1 ameliorates neuroinflammation and motor deficit after traumatic brain injury

Traumatic brain injury (TBI) is a predominant cause of long-term disability in adults, yet the molecular mechanisms underpinning the neuropathological processes associated with it remain inadequately understood. Neutrophil cytosolic factor 1 (NCF1, also known as p47phox) is one of the cytosolic components of NADPH oxidase NOX2. In this study, we observed a reduction in the volume of TBI-induced brain lesions in NCF1-knockout mice compared to controls. Correspondingly, the neuronal loss induced by TBI was mitigated in the NCF1-knockout mice. Behavioral analysis also demonstrated that the motor coordination deficit following TBI was mitigated by the depletion of NCF1. Mechanistically, our findings revealed that NCF1 deficiency attenuated TBI-induced inflammatory responses by inhibiting the release of proinflammatory factors and reducing neutrophil infiltration into the brain parenchyma. Additionally, our results indicated that NCF1 deficiency significantly decreased the levels of reactive oxygen species in neutrophils. Taken together, our findings indicate that NCF1 plays a crucial role in the regulation of brain injury and secondary inflammation post-TBI.

Updated insights into the NLRP3 inflammasome in postoperative cognitive dysfunction: emerging mechanisms and treatments.

Postoperative cognitive dysfunction (POCD) poses a significant threat to patients undergoing anesthesia and surgery, particularly elderly patients. It is characterized by diminished cognitive functions post surgery, such as impaired memory and decreased concentration. The potential risk factors for POCD include age, surgical trauma, anesthetic type, and overall health condition; however, the precise mechanisms underlying POCD remain elusive. Recent studies suggest that neuroinflammation might be a primary pathogenic factor. NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasomes are implicated in exacerbating POCD by promoting the release of inflammatory factors and proteins that initiate pyroptosis, further influencing the disease process. The regulation of NLRP3 inflammasome activity, including its activation and degradation, is tightly controlled through multiple pathways and mechanisms. In addition, autophagy, a protective mechanism, regulates the NLRP3 inflammasome to control the progression of POCD. This review reviews recent findings on the role of the NLRP3 inflammasome in POCD pathogenesis and discusses therapeutic strategies aimed at reducing NLRP3 sources, inhibiting cellular pyroptosis, and enhancing autophagy.