Injuries to the facial nerve present clinical difficulties with frequently unfavorable results. This study uses histological, electrophysiological, and LC-MS/MS-based metabolomic techniques to examine the dose-dependent effects of locally administered minocycline on facial nerve regeneration. For that purpose, the rats were divided into three groups. Following nerve transection and suturing, the rats from Group A received sterile water, those from Group B received 40 μg of minocycline, and those from Group C received 100 μg of minocycline locally on the suture line in 20 μL fibrin gel. Nerve regeneration was evaluated using LC-MS/MS metabolomics and histopathological analyses at the end of the 28th day. Electrophysiological analyses were performed on the 0th day and postoperative 1, 2, and 4 weeks. In the sections of Group A, edema within the myelin sheath and beneath the perineurium were the most conspicuous findings. Vacuolar characteristics within the myelin sheath were also detectable. Groups B and C exhibited preserved architecture with minimal edema. Nerve fiber density was similar across groups (p > 0.05). Metabolomics analyses revealed reduced betaine and elevated proline levels in Group C vs. Group A (p < 0.05). Compound muscle action potential values improved over time, especially in Group B (p = 0.013), peaking at week 2. Both doses of minocycline have been found beneficial on facial nerve regeneration. Although Group C showed superior histological and biochemical outcomes, Group B induced greater clinical and electrophysiological outcomes. We suggest that minocycline is effective on nerve regeneration in a dose-dependent manner. No Level Assigned This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Dimethylacetamide (DMAC) is a polar organic solvent widely used in the production of synthetic fibers and other industrial applications. Its hepatotoxic potential has been well documented in laboratory animals and occupationally exposed workers, establishing DMAC as a recognized industrial hazard. However, evidence regarding its neurological effects remains scarce. We report a clinical case of accidental DMAC inhalation associated with diffuse cortical hyperintensity on brain magnetic resonance imaging, raising concern for direct neurotoxicity. To address this knowledge gap, we investigated the neurotoxic potential of DMAC in a controlled rat model experiment. Animals subjected to repeated intraperitoneal DMAC administration exhibited cortical and subcortical histopathological alterations consistent with neurotoxicity, accompanied by significant hepatic and renal injury. These findings provide the first experimental evidence that DMAC toxicity extends beyond hepatotoxicity to involve the central nervous system and kidneys, highlighting its potential for multi-organ toxicity and reinforcing concerns regarding occupational exposure risks.

PURPOSE:To investigate the cytological and inflammatory effects of topical antiglaucoma medications on the ocular surface by comparing treated and untreated eyes in unilateral glaucoma patients. METHODS:This observational, case-control study involved 69 patients with unilateral glaucoma, receiving monotherapy with prostaglandin analogues. The untreated fellow eyes served as controls. Tear break-up time (TBUT), Schirmer test, conjunctival impression cytology, and tear cytokine levels [interleukin (IL)-1β and IL-6] were assessed in both eyes. Comparisons between treated and untreated eyes, correlations among ocular surface parameters, and linear mixed-effects analyses according to treatment duration were performed. RESULTS:TBUT was significantly lower in treated eyes than in untreated eyes (p < 0.001), whereas Schirmer test results did not differ significantly (p = 0.318). Conjunctival impression cytology analysis showed that goblet cell count was significantly lower (p < 0.001) and Nelson grading was higher (p < 0.001) in the treated eyes. Inflammatory cytokine analysis revealed significantly elevated levels of IL-1β and IL-6 in the treated group (p < 0.001). Goblet cell count correlated positively with TBUT, whereas both cytokines correlated negatively with goblet cell count. Linear mixed-effects analyses showed that longer treatment duration was associated with greater treated-fellow eye divergence in TBUT and IL-6, but not in the other parameters. CONCLUSION:Long-term use of preservative-containing antiglaucoma medications is associated with goblet cell loss, conjunctival squamous metaplasia, increased ocular surface inflammation, and tear film instability, findings that are most consistent with an evaporative-type dry eye pattern. This interpretation is further supported by the concordant findings of conjunctival impression cytology and tear inflammatory cytokine analysis.

Pneumonia-induced sepsis is a major cause of acute kidney injury (AKI), which can lead to high morbidity and mortality. Ceragenins, such as CSA-13, are synthetic mimics of antimicrobial peptides with known antimicrobial and immunomodulatory properties. This study aimed to evaluate the hypothesis that CSA-13, administered intraperitoneally following pneumonia-induced sepsis, was able to induce renal protection in mice. C57/BL6 female mice were randomly categorized into four groups (n = 6/group): (1) healthy control; (2) pneumonia control; (3) pneumonia followed by a low dose of CSA-13; and (4) pneumonia followed by a high dose of CSA-13. We tested CSA-13 for its effects on renal tissue IL-6 (inflammation marker) and plasma levels of cystatin C (renal injury marker). Plasma levels of hyaluronan were measured to evaluate glycocalyx degradation. Cellular integrity was assessed by histological evaluation. We found that (1) both CSA-13 doses successfully restored cystatin C; (2) high and low doses of CSA-13 decreased IL-6 levels to normal levels; (3) plasma hyaluronan remained elevated in treated and untreated mice; and (4) cellular integrity was largely maintained by the administration of either high or low doses of CSA-13. Intraperitoneal administration of CSA-13 decreases IL-6 levels in the kidneys and protects kidney function and cellular integrity in a model of pneumonia-induced sepsis. Plasma hyaluronan levels of infected mice were not substantially altered by the administration of ceragenin. CSA-13 may be helpful as a treatment protocol for pneumonia that inhibits acute kidney injury.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to compromise the efficacy of conventional antibiotics, highlighting the urgent need for alternative antimicrobial strategies. This study aimed to isolate, characterize, and evaluate the therapeutic potential of two strictly lytic bacteriophages, Staphylococcus phages EAS1 and EAS2, against MRSA, including their safety and efficacy in an in vivo myositis model. EAS1 and EAS2 were isolated from wastewater and characterized using transmission electron microscopy, whole-genome sequencing, and in vitro functional assays. Genomic and comparative analyses were performed to assess genome organization and safety-related features. Therapeutic efficacy and toxicity were evaluated in a rat model of MRSA-induced myositis, with assessment of inflammatory mediators and histopathological tissue damage. Both phages exhibited broad and potent lytic activity against S. aureus, including MRSA strains, and demonstrated high physicochemical stability and biocompatibility. Both phages possessed large linear dsDNA genomes (∼138–140 kb) encoding over 240 CDSs without lysogeny, virulence, or antibiotic resistance genes and were classified within the Kayvirus genus based on comparative genomics. In vivo, phage treatment caused no detectable hepatic or renal toxicity. EAS2 treatment led to significant modulation of inflammatory mediators, including TNF-α, IL-10, NF-κB, and COX-2, and resulted in reduced histopathological tissue damage compared with untreated control and vancomycin-treated groups. These findings demonstrate the stability, safety, and therapeutic efficacy of bacteriophages EAS1 and EAS2, particularly EAS2, supporting phage therapy as a promising alternative approach for the treatment of MRSA infections.

OBJECTIVES:Cisplatin is an effective chemotherapeutic agent used in the treatment of various types of cancer; however, it exhibits severe ototoxic side effects. The aim of this study is to investigate the potential protective effects of emodin, a natural anthraquinone derivative, against cisplatin-induced ototoxicity in a rat model. METHODS:Twenty-four female Wistar rats were divided into four groups: control, emodin, cisplatin, and emodin + cisplatin. Auditory brainstem responses (ABR) were measured on days 1, 3, and 7 using click and tone burst stimuli (8-32 kHz). Following sacrifice, cochlear tissues were evaluated through histological and biochemical analyses. For biochemical assessment, total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) were measured. Histological changes were examined using light microscopy. RESULTS:A significant increase in hearing thresholds, severe damage to the histological structure of the cochlea, and elevated total oxidant levels were observed in the cisplatin group (p < 0.05). In the emodin + cisplatin group, compared to the cisplatin group, the increase in hearing thresholds and histological damage were found to be less pronounced (p < 0.05). Furthermore, the increase in total antioxidant levels and the decrease in oxidative stress index support the protective effect of emodin against oxidative stress (p < 0.05). CONCLUSION:Emodin has demonstrated protective effects against cisplatin-induced ototoxicity. These findings highlight the potential of emodin as an otoprotective agent and support its possible application during cisplatin therapy. However, further research is required for clinical implementation.

Mononükleer fagositik sistemin önemli elemanları olan makrofajlar vücudun savunma mekanizmalarının sürdürülmesi için önemlidirler. Güçlü fagositik aktiviteleri ve verimli antijen sunumlarıyla tanınan bu çok yönlü hücreler, etkilerini bağışıklığın ötesine taşıyarak doku gelişimi, onarımı ve homeostazisinde önemli roller oynarlar. Oldukça heterojen bir grup olan makrofajlar, farklı dokuların özel ihtiyaçlarına uyum sağlayarak çeşitli organlarda farklı isimler alırlar. İki ana fenotipe ayrılabilirler: klasik olarak aktive edilmiş (pro-inflamatuar) makrofajlar ve alternatif olarak aktive edilmiş (anti-inflamatuar) makrofajlar. Makrofaj polarizasyonunu kontrol ederek inflamatuar yanıtları düzenlemek makrofajlarla bağlantılı birçok hastalığın engellenmesinde ve tedavisinde etkili olabilir. Bu derlemede makrofajların kökenleri, mikroskobik ve fonksiyonel özellikleri, tipleri, işaretleme yöntemleri ve klinik önemleri ele alınmıştır.

Despite numerous experimental and clinical studies in terms of novel therapeutic strategies, the treatment of acute pancreatitis (AP) is still symptomatic. In the present study, we aimed to evaluate the effects of Punica-granatum L. (pomegranate) and Aronia-melanocarpa (black chokeberry) which both have antioxidant and anti-inflammatory actions on the treatment of AP. Thirty-two rats were divided into 4 groups: Control, AP, pomegranate, and black chokeberry groups. To create AP, L-arginine was administered intraperitoneally. The rats from the pomegranate and black chokeberry groups were administered two doses of pomegranate and black chokeberry extract orally after each L-arginine injection for 7 days. Pancreatic tissues were processed for light and electron microscopic and biochemical evaluations. L-arginine administration resulted in severe necrotic AP characterized by necrosis, apoptosis, and significant increases in serum amylase, and lipase levels as well as tissue total oxidant status (TOS) levels. Degenerated organelles, apoptotic bodies, and myelinic figures were observed by electron microscopic examination. Both pomegranate and black chokeberry had beneficial effects on the treatment of AP via decreasing total histopathological damage score, apoptosis rate, and serum and tissue TOS levels. These beneficial effects of pomegranate and black chokeberry extracts may offer compelling information that may inspire and guide the development of novel therapeutic approaches for the treatment of AP.

The study aimed to investigate the long-term effects of IUGR and consequent catch-up growth on metabolic health by using a comprehensive approach that included histopathological, immunohistochemical, biochemical, and metabolomics analyses. Sprague-Dawley pregnant rats either undergo bilateral uterine artery ligation or a sham surgery on the 19th day of gestation. The offspring reached catch-up growth, kidney samples were collected at postnatal weeks 2, 4, and 8 for analysis. IUGR rats exhibited a spectrum of changes including reduced glomeruli number, proliferating cell number, altered oxidative stress markers, various enzymes involved in Krebs cycle, mitochondrial dynamics, and energy metabolism. Examination of the 8-week-old cohort identified a broader spectrum of metabolic alterations, notably in the biosynthesis of phenylalanine, tyrosine, and tryptophan, phenylalanine, tyrosine, glyoxylate, dicarboxylate, pyruvate, alanine, aspartate, and glutamate metabolism, glycolysis/gluconeogenesis and citrate (TCA) cycle. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, hypertriglyceridemia, cardiovascular diseases, and mental retardation. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies to mitigate the risk of metabolic diseases in individuals with a history of IUGR.

Intrauterine growth restriction (IUGR) is increasingly recognized as a significant risk factor for metabolic disorders in adulthood. Employing a multi-faceted approach encompassing histopathological, immunohistochemical, biochemical, Western-blotting, and metabolomics analyses, this study aimed to elucidate potential metabolite markers of IUGR, and catch-up growth-related metabolic disturbances and the underlying metabolic pathways implicated in IUGR pathogenesis. This study cohort comprised 54 male siblings from 20 Sprague-Dawley female young rats. On the 19th day of gestation, half of the pregnant rats underwent bilateral uterine artery ligation, while the remaining half underwent a simulated surgical intervention involving solely peritoneal incisions. Blood and liver samples were collected from the pups after attaining catch-up growth at the postnatal weeks 2, 4, and 8. IUGR rats exhibited a spectrum of changes including histological abnormalities, altered apoptosis rates, oxidative stress markers, and mitochondrial energy metabolism. Metabolomic analysis revealed dysregulation in multiple metabolic pathways encompassing galactose, propanoate, glycerolipid, cysteine, methionine, and tyrosine metabolism, among others. Notably, disturbances were observed in butanoate, glutathione metabolism, valine, leucine, and isoleucine biosynthesis and degradation, citrate cycle, aminoacyl-tRNA biosynthesis, as well as glycolysis/gluconeogenesis. Our metabolomics analysis provides insights into the potential disease susceptibility of individuals born with IUGR, including obesity, diabetes, heart failure, cancer, mental retardation, kidney and liver diseases, and cataracts. These findings underscore the intricate interplay between intrauterine conditions and long-term metabolic health outcomes, highlighting the need for further investigation into preventive and therapeutic strategies aimed at mitigating the risk of metabolic diseases in individuals with a history of IUGR.

Autophagy, a conserved cellular degradation process, is crucial for various cellular processes such as immune responses, inflammation, metabolic and oxidative stress adaptation, cell proliferation, development, and tissue repair and remodeling. Dysregulation of autophagy is suspected in numerous diseases, including cancer, neurodegenerative diseases, digestive disorders, metabolic syndromes, and infectious and inflammatory diseases. If autophagy is disrupted, for example, this can have serious consequences and lead to chronic inflammation and tissue damage, as occurs in diseases such as Chron's disease and ulcerative colitis. On the other hand, the influence of autophagy on the development and progression of cancer is not clear. Autophagy can both suppress and promote the progression and metastasis of cancer at various stages. From inflammatory bowel diseases to gastrointestinal cancer, researchers are discovering the intricate role of autophagy in maintaining gut health and its potential as a therapeutic target. Researchers should carefully consider the nature and progression of diseases such as cancer when trying to determine whether inhibiting or stimulating autophagy is likely to be beneficial. Multidisciplinary approaches that combine cutting-edge research with clinical expertise are key to unlocking the full therapeutic potential of autophagy in digestive diseases.

The use of stem cells can attenuate testicular injury and promote sperm production. The adipose-derived stromal vascular fraction (SVF) has become an attractive cell source for cell-based therapies. In this study, we aimed to investigate the therapeutic efficacy of SVF on busulfan-induced testicular damage in rats. Twenty-four male rats were randomly divided into control, busulfan, SVF, and busulfan + SVF groups. Testicular damage was induced by intraperitoneal administration of busulfan (35 mg/kg). SVF obtained from human adipose tissue using Lipocube SVF (TM) was injected into rats 5 weeks after busulfan administration. At the end of the 8th week, rats were sacrificed, and histopathological, biochemical, and western blotting analyses were performed. No harmful effects of SVF on healthy testis tissue and sperm parameters were detected. SVF improved busulfan-induced oxidative stress in both testis tissue and serum. SVF injection to damaged testicular tissue resulted in increases in the healthy spermatozoon numbers and decreases in the abnormal tail numbers. Additionally, SVF increased bax/Bcl, DAZL, and TGF-beta 1 levels whereas decreased ATG5 and NF-kB levels. According to the results we obtained in this study, we suggest that SVF is beneficial in restoring damaged tissue by primarily being a multipotent cell source, by inhibiting oxidative stress and converting necrotic cell death to apoptotic cell death. In the future, clinical applications should bring higher benefits. Since SVF is the patient's own tissue, being harmless, it will offer an advantageous supportive treatment option for patients already weakened by cancer and anticancer therapy.

Objective: Aging entails a gradual rise in low-grade inflammation affected by cellular degeneration and death. Inflammaging refers to the chronic, low-grade inflammation that occurs alongside the aging process. This study attempts to evaluate the hepatic and renal histological changes, apoptosis and necroptosis rates, and inflammaging status of 6-week-old and 10-month-old rats. Materials and Methods: This study uses 12 male rats separated into two groups: Young Group (6-week-old rats; n = 6), and Adult Group (10-month-old rats; n = 6). Animals were sacrificed under anesthesia. The rats’ livers and kidneys were removed, and each organ tissue was divided into two parts: one for the microscopic examination (H&E and TUNEL immunohistochemistry) and the other for biochemical determination (tumor necrosis factor-alpha [TNF-α], nuclear factor-kappa beta [NF-𝜅B], interleukin1-Beta [IL-1β], IL6, receptor-interacting serine/threonine protein kinase [RIP], and RIP3). Results: The histological features of the livers and kidneys of the 6-week-old rats were consistent with healthy mammalian organ features, while some histological changes were detected in sections of the 10-month-old rats. The apoptosis rate indicated by TUNEL immunohistochemistry was seen to have increased in the 10-month-old rats, while the necroptosis rate indicated by RIP3 Western-blotting analysis was conversely determined to have decreased. Significant increases in TNF-α and NF-𝜅B levels were consistent with the increased apoptosis rate in the 10-month-old rats compared to the 6-week-old rats. Conclusion: One of the striking results of this study is that the degenerative changes related to aging began to be seen even in 10-month-old rats. The researchers used healthy rats of this age as control subjects as well as to create experimental models.

ObjectiveEndotoxins, products of Gram-negative bacteria, are the primary cause of blood-brain barrier (BBB) damage. In the present study, we aimed to investigate the possible neuroprotection mechanisms of melatonin on BBB damage induced by endotoxemia.MethodsAdult, female Sprague-Dawley rats (n = 42) were separated into four random groups as a control group and three treatment groups. Lipopolysaccharide (7,5 mg/kg/day) was administrated for a single dose to generate a 24-hour sepsis model on rats. Melatonin (10 mg/kg/day) was treated a week before sepsis. Afterward, the dissected brain tissues were examined by histopathological, biochemical, and molecular analyses.ResultsLPS caused weight loss in the groups. As a result, degenerated neurons with cytoplasmic vacuoles and irregular pyknotic nuclei, pale stained necrotic neurons, and vascular congestion were observed in LPS-exposed rats. However, MEL decreased the number of degenerated neurons in treated groups. MEL treatment increased ZO1 and Occludin immunoreactivity while decreasing TLR4 in brain tissues. MEL effect on protein expression was recorded for ZO1 increase and TLR4 decrease in brain tissue compared to LPS groups. MEL also decreased MDA levels in brain tissue.ConclusionsMEL recovered the degenerative damage of sepsis by contributing to blood-brain barrier integrity, and by decreasing inflammation, thus the neuroprotective effects of MEL might provide an experimental basis for clinical applications.

Adipose tissue provides an abundant source of stromal vascular fraction (SVF) cells for immediate administration. It can also give rise to many multipotent adipose-derived stromal cells. SVF is the population of cells obtained from mechanical or enzymatic digestion of lipoaspirate with no necessity for cell culture or expansion. Recently, the heterogeneous cell population found in the SVF gained wide-ranging translational significance in regenerative medicine. Forty-eight male rats were randomly divided into two main groups, including the control and SVF groups. Each group was further divided into four groups as follows: 0th-, 3rd-, 7th-, and 10th-day groups. A skin excision of 1 × 1 cm covering the epidermis and dermis was performed on the back skin. Just after the wound was created, a subepidermal injection of SVF was applied. SVF was obtained from human adipose tissue using Lipocube SVFTM. On the 0th (1 h after the injections), 3rd, 7th, and 10th days, rats were killed, and skin excisions from the wound areas tissues were performed. Histopathological, biochemical, and western blotting analyses were performed on tissues. Our data showed that SVF obtained from a healthy woman improved wound healing in healthy rats. SVF has promoted wound healing mainly because of its antioxidant, antiapoptotic, and fibroblast/myofibroblast stimulating effects. SVF stimulated collagen production and contraction of the wound lips, supporting the closure. Our study provides additional data about the efficacy and pathophysiological and molecular mechanisms of the action of SVF on wound healing in healthy subjects. Our study is an experimental animal study. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

AimOne of the serious complications of sepsis is liver damage and liver failure. This study aimed to evaluate the protective and therapeutic potential of melatonin in rats with lipopolysaccharide-induced sepsis.Main methodsFemale Spraque-Dawley rats received single a dose of 7.5 mg/kg lipopolysaccharide in saline to create a 24-h sepsis model. One of the other groups received melatonin at a dose of 10 mg/kg/day beginning 1 week before sepsis induction to the end of the experiment. The melatonin group received the same doses of melatonin for the same duration but not lipopolysaccharide. The vehicle group received the same doses of saline, the vehicle of melatonin, for the same duration. Twenty-four hours after the last injection, the rats were decapitated. By appropriate histochemical, immunohistochemical, biochemical, and molecular techniques, anti-necrotic, anti-apoptotic, anti-necroptotic, anti-inflammatory, and antioxidant effects of melatonin were assessed.Key findingsLipopolysaccharide has disrupted liver functions by inducing oxidative stress, inflammation, necrotic, apoptotic, and necroptotic cell death, thus disrupting liver functions. Melatonin was found to be beneficial in terms of inhibiting the intrinsic pathway of apoptosis and tissue oxidant levels, stimulating tissue antioxidant enzyme levels, and restoring hepatocyte functions.SignificanceMelatonin, at those doses and duration, was found to be hepatoprotective by mainly modulating oxidative status and apoptosis rate, however, failed to significantly reduce histopathological damage. We suggest that longer-term melatonin administration may produce anti-inflammatory and anti-necrotic effects as well.

Aim: To investigate the effects of adipose tissue-derived stromal vascular fraction on busulfan-induced testicular damage.Main methods: Stromal vascular fraction(SVF) was obtained from human adipose tissue by using Lipocube SVFTM. Twenty-four male rats were divided into 4 groups. In two of the groups, testicular damage was induced by busulfan. SVF was given to one of the groups alone and to one of the groups with busulfan. The rats were sacrificed at the end of the 8th week. Histopathological, biochemical, and western-blotting analyses were performed on testicular tissues and serum.Key findings: SVF alone was not harmful to testis tissue and sperm parameters. On the contrary oxidative stress parameters obtained from the tissue and serum showed supportive effects of SVF on the oxidative status of the healthy tissue. Similarly, SVF improved busulfan-induced increased oxidative stress index of the tissue (p<0.05) and serum (p≤0.001). Additionally, the beneficial effects of SVF on busulfan-induced damage were detected in terms of induced spermatogenesis, increased healthy sperm numbers (p<0.001), and decreased abnormal tail numbers (p<0.001). Significance: Various significant clues related to the beneficial effects of SVF on busulfan-induced testis damage were obtained by using histopathological, immunohistochemical, western-blotting, and sperm analysis methods. Since the volume of the rat testis is very small, injected SVF caused minimal damage. We suggest that larger testicular volume in men should make the application of SVF harmless. SVF which is easily obtainable might be a promising effective therapeutic agent in the removal of the testis and organ damage induced by busulfan toxicity.

Cardiac hypertrophy (CH) is an adaptational enlargement of the myocardium, in exposure to altered stress conditions or in case of injury which can lead to heart failure and death. MicroRNAs (miRNAs) are noncoding RNAs that play a significant role in modulating gene expression. Here, we aimed to identify new miRNAs effective in an experimental CH model and to find an epigenetic biomarker that could demonstrate therapeutic targets responsible for the pathology of heart tissue and serum. In this study, Sprague-Dawley male rats were divided into the training group (TG, n=9) and the control group (CG, n=6). Systolic and diastolic dimensions of the left ventricle and myocardial wall thickness were measured by echocardiography to assess CH. After the exercise program of the rats, miRNA expression measurements and histological analyses were performed. The 25,000 genes in the rat genome were searched using microarray analysis. A total of 128 miRNAs were selected according to the fold change rates, and nine miRNAs were validated for expression analysis. The terminal deoxynucleotidyl transferase dUTP nick (TUNEL) method was used to detect apoptotic cells. Cell proliferation was evaluated by the proliferative cell nuclear antigen (PCNA) method. Necrosis, bleeding, and intercellular edema were detected in TG. The mean histopathological score was higher in TG (p=0.03). There were rarely positive cells for apoptosis of both groups in cardiomyocytes. In the receiver characteristic curve analysis (ROC), the heart tissue rno-miR-290 had an area under the curve (AUC) of 0.920 with 100% sensitivity and 89.90% specificity (p=0.045), rno-miR-194-5p had AUC of 0.940 with 83.33% sensitivity and 100% specificity (p=0.003), and the serum rno-miR-132-3p AUC was 0.880 with 66.67% sensitivity and 100% specificity (p=0.004) in TG. miR-194-5p was used as a therapeutic target for remodeling the cardiac process. While miR-290 contributes to CH as a negative regulator, miR-132 in serum is effective in the pathological and physiological cardiac remodeling process and is a candidate biomarker.

Cis‐diamminedichloroplatinum (II) (cisplatin, Cis) is widely employed to treat several types of cancer. It has many important toxic side effects; one of the most important of which is nephrotoxicity. Clemizole hydrochloride (Clem) as the most potent inhibitor of TRPC5 channels was tested in an animal model of Cis‐induced nephrotoxicity. Rats were divided into the following groups: control; Cis (8 mg/kg); Cis + 1 mg/kg Clem; Cis + 5 mg/kg Clem; Cis + 10 mg/kg Clem. Kidney injury was detected by histopathological and biochemical analysis. Urine urea nitrogen (UUN), creatinine, urine neutrophil gelatinase‐associated lipocalin (NGAL), serum catalase (CAT), and malondialdehyde (MDA) levels were determined by enzyme‐linked immunosorbent assay. Total antioxidant status (TAS) and total oxidant status (TOS) were studied using a colorimetric assay. Nephrin, synaptopodin, and Rac family small GTPase 1 (RAC1) expressions were detected by Western blot analysis. Cis was found to induce histopathological alterations, including tubular degeneration, congestion, hemorrhage, hyaline casts, glomerular collapse, and apoptotic cell death. Clem at a dose of 1 and 5 mg/kg attenuated histopathological alterations. UUN, creatinine, and NGAL levels increased in the Cis‐administered group, while all doses of Clem decreased in those. CAT and TAS levels decreased, while TOS and oxidative stress index levels increased in the Cis‐treated group. A dose of 1 and 5 mg Clem showed antioxidant effects against oxidative stress. Cis induced lipid peroxidation by increasing MDA levels. All doses of Clem reduced MDA levels. Nephrin and synaptopodin expressions were decreased by Cis, and all doses of Clem increased that. All doses of Clem successfully depressed RAC1 expression. Clem showed a highly ameliorating effect on toxicity caused by Cis by blocking TRPC5 calcium channels.

Background:Wound healing following periodontal soft tissue procedures can differ owing to different techniques, the feasibility of which can be determined through detailed macroscopic and microscopic observations. Aims:This study aimed to clinically and histologically evaluate palatal wound healing in rats by secondary intention after excision using a steel scalpel, diode laser, and radiofrequency. Materials and Methods:An excision was made in the edentulous anterior maxilla of 42 4-month-old male Wistar rats weighing 289-428 g. Part of the connective tissue was left in the surgical area to observe the dynamics of secondary intention wound healing. Three experimental groups were established: the steel scalpel, an 810-nm diode laser at a power output of 1.5 W in continuous mode, and a monopolar radiofrequency in a fully rectified waveform at 15 W. Clinical and histological analyses were performed on days 2, 4, and 7. Hemostasis, changes in body weight, defect size, epithelial gap, and inflammatory infiltration were evaluated. Results:The epithelial gap closed completely in all groups on day 7. Bleeding occurred significantly more in the scalpel group (P < 0.001). No significant changes were observed in body weight between the groups. Macroscopically, the mean wound area decreased over time in all groups. Wound healing was significantly slower in the laser group on day 2 and in the radiofrequency group on days 4 and 7 (P < 0.001). Microscopically, the laser created the cleanest wound area, with minimal inflammatory infiltration and no thermal injury. More damage occurred in the connective tissue of the radiofrequency group. Wound healing was observed on day 7 in all groups. Conclusions:Palatal wound healing with secondary intention yielded different outcomes in a rat model when different techniques were used. However, almost complete healing was observed in all wounds, which highlights the importance of the soft tissue left in the surgical area. Wound healing in periodontal soft tissue procedures is not compromised by different techniques, as long as the clinician has sufficient knowledge and experience.