Cinnamic Acid Ameliorates Acetic Acid-induced Inflammatory Response through Inhibition of TLR-4 in Colitis Rat Model.

BACKGROUND: Cinnamic acid, an active compound in cinnamon spp., has anti-inflamatory and antioxidant characteristics and is favorable in managing inflammatory bowel diseases. OBJECTIVE: Evaluate cinnamic acid's effects on colitis in rats. METHODS: To induce colitis in experimental rats, excluding the sham group, a 4% intrarectal solution of acetic acid was administered. The rats were then given oral doses of cinnamic acid at 30, 45, and 90 mg/kg for two days. The animals were assessed for macroscopic and microscopic changes, and the levels of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and myeloperoxidase (MPO) were measured using Eliza kits. Additionally, real-time PCR was performed to examine the gene level of toll-like receptor 4 (TLR-4) in the colon. RESULTS: Effective reduction of inflammation in acetic acid-induced colitis was achieved through cinnamic acid at doses of 45 and 90 mg/kg. The decrease was achieved by inhibiting the activities of TNF-α, IL-6, and MPO while downregulating the expression of TLR-4. It is important to note that macroscopic and microscopic evaluations were significant in determining the effectiveness of cinnamic acid in reducing inflammation. CONCLUSION: Downregulation of inflammatory cytokines and TLR-4 expression may contribute to cinnamic acid's anti-inflammatory effect.

Common gastrointestinal drug-drug interactions in geriatrics and the importance of careful planning.

INTRODUCTION: Polypharmacy, which uses multiple medications to treat chronic illnesses, is common among elderly patients. However, it can lead to drug interactions, especially with gastrointestinal (GI) medicines that are extensively used. These drug interactions can have severe consequences and pose a significant challenge to healthcare providers. Therefore, it is crucial to identify the underlying mechanisms of these interactions and develop strategies to minimize medication errors. AREAS COVERED: We analyzed databases on GI illnesses common in older adults, including GERD, peptic ulcer disease, IBS, IBD, constipation, and diarrhea. Our research identified noteworthy drug interactions and utilized major electronic databases such as USFDA, PubMed, Scopus, and Google Scholar until 15 May 202315 May 2023, along with a review of reference lists. EXPERT OPINION: Aging can affect how the body processes drugs, leading to an increased risk of drug interactions. Therefore, healthcare professionals must carefully evaluate a patient's medical history and health condition to design personalized treatment plans.

The susceptibility of humans to neurodegenerative and neurodevelopmental toxicities caused by organophosphorus pesticides.

The toxicology field is concerned with the impact of organophosphorus (OP) compounds on human health. These compounds have been linked to an increased risk of neurological disorders, including neurodegenerative and neurodevelopmental diseases. This article aims to review studies on the role of OP compounds in developing these neurological disorders and explore how genetic variations can affect susceptibility to the neurotoxicity of these pesticides. Studies have shown that exposure to OP compounds can lead to the development of various neurological disorders, such as Alzheimer's disease (AD), Parkinson's disease (PD), attention deficit hyperactivity disorder (ADHD), autism, intellectual disability, and other developmental neurotoxicities. Apart from inhibiting the cholinesterase enzyme, OP compounds are believed to cause other pathological mechanisms at both the extracellular level (cholinergic, serotonergic, dopaminergic, glutamatergic, and GABAergic synapses) and the intracellular level (oxidative stress, mitochondrial dysfunction, inflammation, autophagy, and apoptosis) that contribute to these disorders. Specific genetic polymorphisms, including PON1, ABCB1, NOS, DRD4, GST, CYP, and APOE, have increased the risk of developing OP-related neurological disorders.

Alginate/gum arabic-based biomimetic hydrogel enriched with immobilized nerve growth factor and carnosine improves diabetic wound regeneration.

Diabetic foot ulcers (DFUs) often remain untreated because they are difficult to heal, caused by reduced skin sensitivity and impaired blood vessel formation. In this study, we propose a novel approach to manage DFUs using a multifunctional hydrogel made from a combination of alginate and gum arabic. To enhance the healing properties of the hydrogel, we immobilized nerve growth factor (NGF), within specially designed mesoporous silica nanoparticles (MSN). The MSNs were then incorporated into the hydrogel along with carnosine (Car), which further improves the hydrogel's therapeutic properties. The hydrogel containing the immobilized NGF (SiNGF) could control the sustain release of NGF for >21 days, indicating that the target hydrogel (AG-Car/SiNGF) can serve as a suitable reservoir managing diabetic wound regeneration. In addition, Car was able to effectively reduce inflammation and significantly increase angiogenesis compared to the control group. Based on the histological results obtained from diabetic rats, the target hydrogel (AG-Car/SiNGF) reduced inflammation and improved re-epithelialization, angiogenesis, and collagen deposition. Specific staining also confirmed that AG-Car/SiNGF exhibited improved tissue neovascularization, transforming growth factor-beta (TGFß) expression, and nerve neurofilament. Overall, our research suggests that this newly developed composite system holds promise as a potential treatment for non-healing diabetic wounds.

Development of a Novel Histatin-5 Mucoadhesive Gel for the Treatment of Oral Mucositis: In Vitro Characterization and In Vivo Evaluation.

Antimicrobial peptides have appeared to be promising candidates for therapeutic purposes due to their broad antimicrobial activity and non-toxicity. Histatin-5 (Hst-5) is a notable salivary antimicrobial peptide that exhibited therapeutic properties in the oral cavity. Oral mucositis is an acute inflammation of the oral cavity, following cancer therapy. The current treatment methods of oral mucositis have low effectiveness. The aim of this study was to design, formulate and characterize a mucoadhesive gel delivery system for Hst-5 usage in the treatment of oral mucositis. Carbopol 934 and hydroxypropyl methylcellulose (HPMC) have been used in the development of a Hst-5 mucoadhesive gel that was optimized by using Box-Behnken design. The optimized formulation was evaluated in-vitro, based on mucoadhesive strength, viscoelasticity, spreadability, release rate, peptide secondary structure analysis, antimicrobial activity, and storage stability. The efficacy of Hst-5 gel was assessed in vivo in a chemotherapy-induced mucositis model. The results showed a sustained release of Hst-5 from the new formulation. Hst-5 gel exerted antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The histopathological, immunohistochemical and statistical analysis showed that the Hst-5 gel had wound healing activity in vivo. The findings of this study indicate that the mentioned compound possesses promising potential as a novel and efficient therapeutic agent in managing oral mucositis. Moreover, the results suggest that the compound is commercially feasible for further development and utilization.

Metformin ameliorates cardiopulmonary toxicity induced by chlorpyrifos.

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

Microfluidically fabricated fibers containing pancreatic islets and mesenchymal stromal cells improve longevity and sustained normoglycemia in diabetic rats.

Type 1 diabetes mellitus is an autoimmune disease characterized by the loss of pancreatic isletßcells. Insulin injections and pancreas transplants are currently available therapies. The former requires daily insulin injections, while the latter is constrained by donor organ availability. Islet transplantation is a promising alternative treatment for type 1 diabetes mellitus that may overcome the limitations of previous techniques. Two challenges, however, must be addressed: limited cell retention as a result of the immune response and limited function of the transplanted cells that survive. To address these problems, we developed a microfluidic technology for a one-step generation of islet-laden fibers to protect them from the immune response. This approach enables continuous generation of microfibers with a diameter suitable for islet encapsulation (275µm). We, then, transplanted islet-laden fibers into diabetic Wistar rats. While islet-laden fibers alone were unable to restore normoglycemia in diabetic rats, adding mesenchymal stromal cells (MSCs) restored normoglycemia for an extended time. It increased the animals' lifespan by up to 75 d. Additionally, it improved the glucose-stimulated response of islets to the point where there was no significant difference between the treatment group and the healthy animals. Additionally, the presence of MSCs suppressed the immune response, as seen by decreased levels of pro-inflammatory cytokines such as tumor necrosis factor-α. Taken together, these fibers including islet and MSCs provide a versatile platform for concurrently improving cell preservation and functioning followingin vivotransplantation.

Budesonide-Loaded Hyaluronic Acid Nanoparticles for Targeted Delivery to the Inflamed Intestinal Mucosa in a Rodent Model of Colitis.

The aim of the present study was to investigate the therapeutic potential of budesonide- (BDS-) loaded hyaluronic acid nanoparticles (HANPs) for treatment of inflammatory bowel disease (IBD) using an acute model of colitis in rats. The therapeutic efficacy of BDS-loaded HANPs in comparison with an aqueous suspension of the drug with the same dose (30 µg/kg) was investigated 48 h following induction of colitis by intrarectal administration of acetic acid 4% in rats. Microscopic and histopathologic examinations were conducted in inflamed colonic tissue. Tissue concentration of tumor necrosis factor (TNF)-α was assessed by ELISA assay kit, while the activity of myeloperoxidase (MPO) was measured spectrophotometrically. Results from in vivo evaluations demonstrated that administrations of BDS-HANPs ameliorated the general endoscopic appearance, quite close to the healthy animals with no signs of inflammation and reduced the cellular infiltration, as well as the TNF-α level, and the MPO activity. It was found that delivery by BDS-loaded HANPSs alleviated the induced colitis significantly better than the same dose of the free drug. These data further suggest the potential of HANPs as a targeted drug delivery system to the inflamed colon mucosa.

A systematic review of mechanistic studies on the relationship between pesticide exposure and cancer induction.

INTRODUCTION: Pesticides are toxic and biological substances used for mitigating harmful pests. Their application in agricultural fields and homes increased environmental pollution. Studies showed their harmful effects on human health, specifically children, who are more vulnerable than adults. The International Agency for Research on Cancer (IARC) has introduced several pesticides as carcinogens. This study aims to systematically summarize and review all studies related to pesticides and cancer. METHODOLOGY: This systematic review is based on PRISMA rules. Three central databases were employed to find studies on pesticide exposure and cancer correlation published from 2017 to September 2022. RESULTS: After reviewing several studies, we found that most studies revealed a significant relationship between pesticide exposure and an increased cancer incidence rate. Among the most studied group of pesticides is organochlorine (OC) pesticides. OC pesticides and their residues could significantly increase cancer in children and adults. Mechanistic studies revealed that pesticides could increase the risk of different cancers by genetics, like an increased expression of some genes like p21, p53 or epigenetic impairments. Cell cycle impairments like expanding the G1 to S phase transition are another mechanism of causing cancer. DNA methylation and histone modifications increase the risk of numerous cancers. CONCLUSION: Based on epidemiological studies, pesticides are a significant concern to human health, specifically cancer development, and should be more restrained. Their most reported mechanism of action were genetic and epigenetic impairments which cause cancers.

The electrocardiographic, hemodynamic, echocardiographic, and biochemical evaluation of treatment with edaravone on acute cardiac toxicity of aluminum phosphide.

Aluminum phosphide (AlP) poisoning can be highly fatal due to its severe toxicity to the heart. Based on the evidence, edaravone (EDA) has protective effects on various pathological conditions of the heart. This research aimed to examine the potential protective effects of EDA on AlP-induced cardiotoxicity in rats. The rats were divided into six groups, including almond oil (control), normal saline, AlP (LD50), and AlP + EDA (20, 30, and 45 mg/kg). Thirty minutes following AlP poisoning, the electrocardiographic (ECG), blood pressure (BP), and heart rate (HR) parameters were examined for 180 min. The EDA was injected 60 min following the AlP poisoning intraperitoneally. Also, 24 h after poisoning, echocardiography was carried out to evaluate the ejection fraction (EF), stroke volume (SV), and cardiac output (CO). The biochemical and molecular parameters, such as the activities of the mitochondrial complexes, reactive oxygen species (ROS), apoptosis and necrosis, and troponin I and lactate levels, were also examined after 12 and 24 h in the heart tissue. According to the results, AlP-induced ECG abnormalities, decrease in blood pressure, heart rate, SV, EF%, and CO were significantly improved with EDA at doses of 30 and 45 mg/kg. Likewise, EDA significantly improved complex I and IV activity, apoptosis and necrosis, ROS, troponin I, and lactate levels following AlP-poisoning (p < 0.05). Also, the mean survival time was increased following EDA treatment, which can be attributed to the EDA's protective effects against diverse underlying mechanisms of phosphine-induced cardiac toxicity. These findings suggest that EDA, by ameliorating heart function and modulating mitochondrial activity, might relieve AlP-induced cardiotoxicity. Nonetheless, additional investigations are required to examine any potential clinical advantages of EDA in this toxicity.

Antidiabetic and neuroprotective effects of a novel repaglinide analog.

Repaglinide (RPG) is an oral insulin secretagogue used in the treatment of diabetes. In this study, a new RPG analog was synthesized. Its antidiabetic and neuroprotective effects on dorsal root ganglions (DRG) in streptozotocin (STZ)-induced diabetic rats were examined compared to RPG. To assess the effects of 2-methoxy-4-(2-((3-methyl-1-(2-(piperidin-1-yl)phenyl)butyl)amino)-2-oxoethoxy)benzoic acid (OXR), the impact of OXR on oxidative stress biomarkers, motor function, and the expression of the glutamate dehydrogenase 1 (GLUD1), SLC2A2/glucose transporter 2 (GLUT2), and glucokinase (GCK) genes in STZ-induced diabetic rats were assessed. DRGs were examined histologically using hemotoxylin and eosin staining. Molecular docking was used to investigate the interactions between OXR and the binding site of RPG, the ATP-sensitive potassium (KATP) channel. Following 5 weeks of treatment, OXR significantly increased the level of total antioxidant power, decreased reactive oxygen species, and lipid peroxidation in the DRGs of diabetic rats. OXR restored STZ-induced pathophysiological damages in DRG tissues. Administration of OXR improved motor function of rats with diabetic neuropathy. Administration of 0.5 mg/kg OXR reduced blood glucose while promoting insulin, mainly through upregulation of messenger RNA expression of GLUD1, GLUT2, and GCK in the pancreas. Molecular docking revealed a favorable binding mode of OXR to the KATP channel. In conclusion, OXR has neuroprotective effects in diabetic rats by lowering oxidative stress, lowering blood glucose, and stimulating insulin secretion. We report that 0.5 mg/kg OXR administration was the most effective concentration of the compound in this study. OXR may be a promising target for further research on neuroprotective antidiabetic molecules.

Epigenetic effects of graphene oxide and its derivatives: A mini-review.

Graphene oxide (GO), an engineered nanomaterial, has a two-dimensional structure with carbon atoms arranged in a hexagonal array. While it has been widely used in many industries, such as biomedicine, electronics, and biosensors, there are still concerns over its safety. Recently, many studies have focused on the potential toxicity of GO. Epigenetic toxicity is an important aspect of a material's toxicological profile, since changes in gene expression have been associated with carcinogenicity and disease progression. In this review, we focus on the epigenetic alterations caused by GO, including DNA methylation, histone modification, and altered expression of non-coding RNAs. GO can affect DNA methyltransferase activity and disrupt the methylation of cytosine bases in DNA strands, leading to alteration of genome expression. Modulation of histones by GO, targeting histone deacetylase and demethylase, as well as dysregulation of miRNA and lncRNA expression have been reported. Further studies are required to determine the mechanisms of GO-induced epigenetic alterations.

A Systematic Review of Nonclinical Studies on the Effect of Curcumin in Chemotherapy- induced Cardiotoxicity.

BACKGROUND: Various anticancer drugs are effective therapeutic agents for cancer treatment; however, they cause severe toxicity in body organs. Cardiotoxicity is one of the most critical side effects of these drugs. Based on various findings, turmeric extract has positive effects on cardiac cells. OBJECTIVE: This study aims to evaluate how curcumin, as the main component of turmeric, may affect chemotherapy- induced cardiotoxicity. METHODS: A database search was performed up to April 2021 using "curcumin OR turmeric OR Curcuma longa" and "chemotherapy-induced cardiac disease", including their equivalents and similar terms. After screening the total articles obtained from the electronic databases, 25 relevant articles were included in this systematic review. RESULTS: The studies demonstrate lower body weight and increased mortality rates due to doxorubicin administration. Besides, cancer therapeutic agents induced various morphological and biochemical abnormalities compared to the non-treated groups. Based on most of the obtained results, curcumin at nontoxic doses can protect the cardiac cells mainly through modulating antioxidant capacity, regulation of cell death, and antiinflammatory effects. Nevertheless, according to a minority of findings, curcumin increases the susceptibility of the rat cardiomyoblast cell line (H9C2) to apoptosis triggered by doxorubicin. CONCLUSION: According to most nonclinical studies, curcumin could potentially have cardioprotective effects against chemotherapy-induced cardiotoxicity. However, based on limited, contradictory findings demonstrating the function of curcumin in potentiating doxorubicin-induced cardiotoxicity, well-designed studies are needed to evaluate the safety and effectiveness of treatment with new formulations of this compound during cancer therapy.

Molecular Evidence on the Inhibitory Potential of Metformin against Chlorpyrifos-Induced Neurotoxicity.

Chlorpyrifos (CPF) is an organophosphorus (OP) pesticide, resulting in various health complications as the result of ingestion, inhalation, or skin absorption, and leads to DNA damage and increased oxidative stress. Metformin, derived from Galega officinalis, is reported to have anti-inflammatory and anti-apoptotic properties; thus, this study aimed to investigate the beneficial role of metformin in neurotoxicity induced by sub-acute exposure to CPF in Wistar rats. In this study, animals were divided into nine groups and were treated with different combinations of metformin and CPF. Following the 28 days of CPF and metformin administration, brain tissues were separated. The levels of inflammatory biomarkers such as tumor necrosis factor alpha (TNFα) and interleukin 1ß (IL-1ß), as well as the expression of 5HT1 and 5HT2 genes, were analyzed. Moreover, the levels of malondialdehyde (MDA), reactive oxygen species (ROS), and the ADP/ATP ratio, in addition to the activity of acetylcholinesterase (AChE) and superoxide dismutase (SOD), were tested through in vitro experiments. This study demonstrated the potential role of metformin in alleviating the mentioned biomarkers, which can be altered negatively as a result of CPF toxicity. Moreover, metformin showed protective potential in modulating inflammation, as well as oxidative stress, the expression of genes, and histological analysis, in a concentration-dependent manner.

Polycystic Ovary Syndrome: A Comprehensive Review of Pathogenesis, Management, and Drug Repurposing.

Polycystic ovary syndrome (PCOS) is an endocrine-gynecology disorder affecting many women of childbearing age. Although a part of the involved mechanism in PCOS occurrence is discovered, the exact etiology and pathophysiology are not comprehensively understood yet. We searched PubMed for PCOS pathogenesis and management in this article and ClinicalTrials.gov for information on repurposed medications. All responsible factors behind PCOS were thoroughly evaluated. Furthermore, the complete information on PCOS commonly prescribed and repurposed medications is summarized through tables. Epigenetics, environmental toxicants, stress, diet as external factors, insulin resistance, hyperandrogenism, inflammation, oxidative stress, and obesity as internal factors were investigated. Lifestyle modifications and complementary and alternative medicines are preferred first-line therapy in many cases. Medications, including 3-hydroxy-3-methyl-3-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors, thiazolidinediones, sodium-glucose cotransporter-2 inhibitors, dipeptidyl peptidase-4 inhibitors, glucose-like peptide-1 receptor agonists, mucolytic agents, and some supplements have supporting data for being repurposed in PCOS. Since there are few completed clinical trials with a low population and mostly without results on PCOS repurposed medications, it would be helpful to do further research and run well-designed clinical trials on this subject. Moreover, understanding more about PCOS would be beneficial to find new medications implying the effect via the novel discovered routes.

Combination therapy of cisplatin and resveratrol to induce cellular aging in gastric cancer cells: Focusing on oxidative stress, and cell cycle arrest.

Background: As a medical dilemma, gastric cancer will have 7.3 million new cases in 2040. Despite the disease's high economic and global burden, conventional chemotherapy regimens containing cisplatin have insufficient effectiveness and act non-specifically, leading to several adverse drug reactions To address these issues, the biological efficacy of the cisplatin-resveratrol combination was tested. Methods: To find IC50, gastric adenocarcinoma cells (AGS) were exposed to different concentrations of resveratrol and cisplatin. Anti-cancer and anti-metastatic effects of 100 M resveratrol with concentrations of cisplatin (25, 50, and 100 g/ml) were studied by assessing ß-galactosidase and telomerase activities, senescence and migration gene expression, reactive oxygen species (ROS) level, and cell cycle arrest. Results: Co-administration of cisplatin and resveratrol increased ß-galactosidase activity, ROS level as a key marker of oxidative stress, p53, p38, p16, p21, and MMP-2 gene expression, and induced G0/G1 cell cycle arrest. Additionally, telomerase activity, pro-inflammatory gene expression, and cell invasion were suppressed. The best results were achieved with 100 g/ml cisplatin co-administered with resveratrol. Conclusion: The current study proved the synergistic effect of the cisplatin-resveratrol combination on suppressing metastasis and inducing apoptosis and cell senescence through targeting P38/P53 and P16/P21 pathways. Such promising results warrant translation to animal models and the clinic. This may lead to cost-effective, available, and accessible treatment regimens with targeted action and the fewest ADRs.

A Novel Approach for Designing Electrochemical Aptamer-Based Biosensor for Ultrasensitive Detection of Zearalenone as a Prevalent Estrogenic Mycotoxin.

BACKGROUND: Zearalenone is a well-known estrogenic mycotoxin produced by Fusarium species, a serious threat to the agricultural and food industries worldwide. Zearalenone, with its known metabolites, is a biomarker of exposure to certain fungi, primarily through food. It has considerable toxic effects on biological systems due to its carcinogenicity, mutagenicity, renal toxicity, teratogenicity, and immunotoxicity. INTRODUCTION: This study aims to design a simple, quick, precise, and cost-effective method on a biosensor platform to evaluate the low levels of this toxin in foodstuffs and agricultural products. METHODS: An aptamer-based electrochemical biosensor was introduced that utilizes screen-printed gold electrodes instead of conventional electrodes. The electrodeposition process was employed to develop a gold nanoparticle-modified surface to enhance the electroactive surface area. Thiolated aptamers were immobilized on the surface of gold nanoparticles, and subsequently, the blocker and analyte were added to the modified surface. In the presence of a redox probe, electrochemical characterization of differential pulse voltammetry, cyclic voltammetry, and electrochemical impedance spectroscopy were used to investigate the various stages of aptasensor fabrication. RESULTS: The proposed aptasensor for zearalenone concentration had a wide linear dynamic range covering the 0.5 pg/mL to 100 ng/mL with a 0.14 pg/mL detection limit. Moreover, this aptasensor had high specificity so that a non-specific analyte cannot negatively affect the selectivity of the aptasensor. CONCLUSION: Overall, due to its simple design, high sensitivity, and fast performance, this aptasensor showed a high potential for assessing zearalenone in real samples, providing a clear perspective for designing a portable and cost-effective device.

Mesenchymal stem cells' seeded amniotic membrane as a tissue-engineered dressing for wound healing.

Different biomaterials have been used as biological dressing for wound regeneration. For many decades, human amniotic membrane graft (AM) has been widely applied for treating acute and chronic wounds. It has minimal toxicity and immunogenicity, supports mesenchymal cell in-growth, improves epidermal cell adherence and proliferation, and finally is inexpensive and readily available. Enrichment of tissue grafts with the stem cells is a new approach to improve their regenerative effects. This animal study aimed at investigating feasibility, safety, and efficacy of tissue-engineered dressings composed of AM and two different types of mesenchymal stem cells (MSCs) in the excisional wound model in rats. Human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs) were manufactured from the donated adipose and placenta tissues respectively. After cell characterization, MSCs were seeded on acellular AM (AAM) and cultivated for 5 days. Excisional wound model was developed in 24 male Wistar rats that were randomly classified into four groups including control, AAM, ADMSCs + AAM, and PLMSCs + AAM (n = 6 in each group). Tissue-engineered constructs were applied, and photographs were taken on days 0, 7, and 14 for observing the wound healing rates. In days 7 and 14 post-treatment, three rats from each group were euthanized, and wound biopsies were harvested, and histopathologic studies were conducted. The results of wound closure rate, re-epithelialization, angiogenesis, and collagen remodeling demonstrated that in comparison with the control groups, the MSC-seeded AAMs had superior regenerative effects in excisional wound animal model. Between MSCs group, the PLMSCs showed better healing effect. Our data suggested that seeding of MSCs on AAM can boosts its regenerative effects in wound treatment. We also found that PLMSCs had superior regenerative effects to ADMSc in the rat model of excisional wound.

Electrocardiographic, hemodynamic, and biochemical evidence on the protective effects of exenatide against phosphine-induced cardiotoxicity in rat model.

Aluminum phosphide (AlP) poisoning can be deadly in most cases targeting the heart. To overcome AlP toxicity, exenatide has been studied in the present study due to its pleiotropic effects on cardiac damages. In this study, the rats were exposed to LD50 of AlP (10 mg/kg) by gavage, and exenatide at doses (0.05, 0.1, and 0.2 mg/kg) injected intraperitoneally 30 min after poisoning. The cardiac parameters including heart rate (HR), blood pressure (BP), QRS, corrected QT (QTc), and ST were monitored for 180 min. Blood glucose level was measured in the study groups 30 min after exenatide injection. Evaluation of biochemical parameters including mitochondrial complexes I, II, and IV activities, adenosine diphosphate (ADP)/adenosine triphosphate (ATP) ratio, malondialdehyde (MDA), apoptosis, lactate, troponin I, and brain natriuretic peptide (BNP) was done on heart tissues after 12 and 24 h. Additionally, the tissues were analyzed for any pathological damages including necrosis, hemorrhage, or hyperemia 24 h post-treatment. Our results showed that AlP-induced HR, BP, and electrocardiographic changes were improved by exenatide at all doses. The blood glucose levels of poisoned animals reached control levels after exenatide treatment. Besides, treatment with exenatide at all doses improved complexes I and IV activity, ADP/ATP ratio, and apoptosis. Malondialdehyde, lactate, troponin I, and BNP levels were also diminished after exenatide co-treatment in poisoned animals. On the other hand, administration of exenatide doses improved the histopathology of AlP-induced tissues. Based on our findings, exenatide has a protective effect against phosphine-induced cardiotoxicity in an almost dose-dependent way. However, further investigations are needed on the potential clinical use of exenatide in this poisoning.

A systematic review of clinical and laboratory findings of lead poisoning: lessons from case reports.

Lead is one of the most toxic heavy metals in the environment. The present review aimed to highlight hazardous pollution sources, management, and review symptoms of lead poisonings in various parts of the world. The present study summarized the information available from case reports and case series studies from 2009 to March 2020 on the lead pollution sources and clinical symptoms. All are along with detoxification methods in infants, children, and adults. Our literature compilation includes results from 126 studies on lead poisoning. We found that traditional medication, occupational exposure, and substance abuse are as common as previously reported sources of lead exposure for children and adults. Ayurvedic medications and gunshot wounds have been identified as the most common source of exposure in the United States. However, opium and occupational exposure to the batteries were primarily seen in Iran and India. Furthermore, neurological, gastrointestinal, and hematological disorders were the most frequently occurring symptoms in lead-poisoned patients. As for therapeutic strategies, our findings confirm the safety and efficacy of chelating agents, even for infants. Our results suggest that treatment with chelating agents combined with the prevention of environmental exposure may be an excellent strategy to reduce the rate of lead poisoning. Besides, more clinical studies and long-term follow-ups are necessary to address all questions about lead poisoning management.