Investigating the level of vitamin D receptor gene expression in two tumoral and healthy breast tissues in breast cancer patients and its association with prognostic factors.

BACKGROUND: Breast cancer is one of the most common cancers known among women. This study aimed to investigate the level of vitamin D receptor gene expression in two tumoral and healthy breast tissues in breast cancer patients and its association with prognostic factors. METHODS: This descriptive cross-sectional study was conducted in 2022 on 50 patients with high suspicion of breast cancer who were candidates for mastectomy and lumpectomy in a learning hospital. From the patients, two tissue samples were prepared, and there was a total of 100 samples. The samples were subjected to H/E staining and evaluated by a pathologist. The presence or absence of malignancy in each sample was confirmed by two pathologists, and HER2/ER/PR indices were determined. Descriptive and analytical statistical methods and SPSS version 22 software were used. RESULTS: The average age of the patients was 51.60 ± 11.22 years old, and the average tumor size was 3.17 ± 1.28. Most tumors were grade 2 (48%). The expression of HER2, ER, and PR was positive in 24, 64, and 54%, respectively. The largest number of cases were in stage 2A. The expression level of vitamin D receptor (VDR) gene in healthy tissue (2.08 ± 1.01) was higher than tumoral tissue (0.25 ± 1.38) (P = 0.001). In tumoral and healthy tissue, VDR expression was not significant according to tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size. CONCLUSIONS: The expression level of VDR in healthy tissue was significantly higher than tumoral tissue. However, there was no significant relationship between VDR and tumor grade, HER2, ER, PR, LVI, LN, disease stage, age, and tumor size.

Impact of Season Variation on Semen Quality: A Comprehensive Retrospective Analysis of Data From Patients at an Eastern Iranian Tertiary Care Fertility Center Over a Decade.

Seasonal changes are assumed to affect various sperm characteristics based on photoperiods, temperature, and air pollution. According to the literature, most studies were performed on populations of Western countries, and there are limited studies performed in the Middle East with variable results. This study evaluated the seasonality of sperm characteristics among men of reproductive age in an andrology center in Kerman, Iran, where the seasonal temperature varies significantly, with average temperatures ranging from 50 °F (10 °C) to 75.2 °F (24 °C). We retrospectively evaluated the sperm analysis test record. Sperm samples were obtained from 2,948 men during 10 years, excluding those with azoospermia. Samples were assessed for volume, concentration, motility, and morphology according to the World Health Organization (WHO) criteria. We performed a comprehensive comparative literature review of the studies investigating the association between seasonal variation and sperm quality. The mean semen volume was higher in the summer compared with other seasons (p = .04). The mean percentage of sperm motility was higher in the spring and less in winter (p = .03). Sperm morphology-related parameters, measured by the percent of normal morphology, were significantly better in winter (p = .03). Our findings suggest seasonality of sperm characteristics among men of fertility age. Semen volume, motility, and morphology were affected by the photoperiod of reproductive seasons. Results might support the influential role of seasonal variations in the possibility of fertility, especially among those using assisted reproductive technologies and those with oligospermia.

Hsa-miR-194-5p and hsa-miR-195-5p are down-regulated expressed in high dysplasia HPV-positive Pap smear samples compared to normal cytology HPV-positive Pap smear samples.

BACKGROUND: The human papillomavirus (HPV) infection may affect the miRNA expression pattern during cervical cancer (CC) development. To demonstrate the association between high-risk HPVs and the development of cervix dysplasia, we examined the expression patterns of hsa-miR-194-5p and hsa-miR-195-5p in Pap smear samples from southeast Iranian women. We compared samples that were HPV-positive but showed no abnormality in the cytological examination to samples that were HPV-positive and had severe dysplasia. METHODS: Pap smear samples were obtained from 60 HPV-positive (HPV-16/18) patients with histologically confirmed severe dysplasia (cervical intra-epithelial neoplasia (CIN 3) or carcinoma in situ) and the normal cytology group. The expression of hsa-miR-194-5p and hsa-miR-195-5p was analyzed by real-time quantitative PCR, using specific stem-loop primers and U6 snRNA as the internal reference gene. Clinicopathological features were associated with miRNA expression levels. Furthermore, functional enrichment analysis was conducted using in silico tools. The Kaplan-Meier survival method was also obtained to discriminate survival-significant candidate miRNAs in CC, and receiver operating characteristic (ROC) curves were constructed to assess the diagnostic value. RESULTS: Compared to HPV-positive cytologically normal Pap smear samples, hsa-miR-194-5p and hsa-miR-195-5p relative expression decreased significantly in HPV-positive patients with a severe dysplasia Pap smear. Kaplan-Meier analysis indicated a significant association between the miR-194 decrease and poor CC survival. In essence, ROC curve analysis showed that miR-194-5p and miR-195-5p could serve as valuable markers for the development of cervix dysplasia in individuals who are positive for high-risk HPVs. CONCLUSIONS: This study revealed that hsa-miR-194-5p and hsa-miR-195-5p may possess tumor suppressor capabilities in the context of cervical dysplasia progression. However, it remains uncertain whether these microRNAs are implicated in the transition of patients with high dysplasia to cervical cancer. We also showed the potential capability of candidate miRNAs as novel diagnostic biomarkers related to cervical dysplasia progression.

Time Course of Biochemical and Metabolic Parameters During and After COVID-19.

BACKGROUND: Long COVID is characterized by the persistence of symptoms among individuals who are infected with the SARS-CoV-2 virus. The enduring impact of these long-term effects on the health and well-being of those affected cannot be denied. METHOD: About 470 patients with SARS-CoV-2 were consecutively recruited in this longitudinal study. The participants were entered into moderate, severe, and critical groups. 235 out of 470 participants were female. The levels of fasting blood sugar (FBS), alanine transaminase (SGPT), aspartate aminotransferase (SGOT), alkaline phosphatase (ALP), creatinine (Cr), urea, uric acid (UA), and total protein (TP) were measured during hospitalization and again at one and three months after infection. The levels of Zn and hemoglobin A1c (HbA1c) were also measured only during hospitalization. RESULT: COVID-19 severity was associated with high levels of glucose, urea, Cr, ALT, AST, ALP, and HbA1c, and low levels of Zn, UA, and TP. There were significant sex differences for these markers at all three-time points. Glucose, urea, Cr, ALT, AST, and ALP all decreased three months after infection, whereas the levels of UA and TP returned towards normal. CONCLUSION: COVID-19 infection affects the levels of multiple biochemical factors in a gender-dependent manner. The biochemical changes become more tangible with increasing disease severity, and several of these predict mortality. Levels begin to return to normal after the acute phase of the disease, but in some individuals, at three months, several markers were still not within the normal range. Whether the trajectory of these changes can predict long COVID requires further testing.

Comparison of cytotoxicity of Miltefosine and its niosomal form on chick embryo model.

Various drugs have been used for the treatment of leishmaniasis, but they often have adverse effects on the body's organs. In this study, we aimed to explore the effects of one type of drug, Miltefosine (MIL), and its analogue or modifier, liposomal Miltefosine (NMIL), on several fetal organs using both in silico analysis and practical tests on chicken embryos. Our in silico approach involved predicting the affinities of MIL and NMIL to critical proteins involved in leishmaniasis, including Vascular Endothelial Growth Factor A (VEGF-A), the Kinase insert domain receptor (KDR1), and apoptotic-regulator proteins (Bcl-2-associate). We then validated and supported these predictions through in vivo investigations, analyzing gene expression and pathological changes in angiogenesis and apoptotic mediators in MIL- and NMIL-treated chicken embryos. The results showed that NMIL had a more effective action towards VEGF-A and KDR1 in leishmaniasis, making it a better candidate for potential operative treatment during pregnancy than MIL alone. In vivo, studies also showed that chicken embryos under MIL treatment displayed less vascular mass and more degenerative and apoptotic changes than those treated with NMIL. These results suggest that NMIL could be a better treatment option for leishmaniasis during pregnancy.

Implication of Novel BMP15 and GDF9 Variants in Unexpected Poor Ovarian Response.

Unexpected poor ovarian response (UPOR) occurs when nine or fewer oocytes are retrieved from a young patient with normal ovarian reserve. Bone morphogenetic protein15 (BMP15) and growth differentiation factor 9 (GDF9) are two oocyte-specific factors with pivotal role in folliculogenesis. The aim of this study was to assess the relation between BMP15 and GDF9 variants with UPOR. Hundred women aged ≤ 39 with AMH ≥ 1.27 IU/ml participated as UPOR and normal ovarian responders (NOR) based on their oocyte number. Each group consisted of 50 patients. After genomic DNA extraction, the entire exonic regions of BMP15 and GDF9 were amplified and examined by direct sequencing. Western blotting was performed to determine the expression levels of BMP15 and GDF9 in follicular fluid. Additionally, in silico analysis was applied to predict the effect of discovered mutations. From four novel variants of BMP15 and GDF9 genes, silent mutations (c.744 T > C) and (c.99G > A) occurred in both groups, whereas missense variants: c.967-968insA and c.296A > G were found exclusively in UPORs. The latter variants caused reduction in protein expression. Moreover, the mutant allele (T) in a GDF9 polymorphism (C447T) found to be more in NOR individuals (58% NOR vs. 37% UPOR (OR = 2.3, CI 1.32-4.11, p = 0.004).The novel missense mutations which were predicted as damaging, along with other mutations that happened in UPORs might result in ovarian resistance to stimulation. The mutant allele (T) in C447T polymorphism has a protective effect. It can be concluded that there is an association between BMP15 and GDF9 variants and follicular development and ovarian response.

Preparation and Evaluation of Preventive Effects of Inhalational and Intraperitoneal Injection of Myrtenol Loaded Nano-Niosomes on Lung Ischemia-Reperfusion Injury in Rats.

INTRODUCTION: Ischemia-reperfusion injury (IRI) is directly related to forming reactive oxygen species, endothelial cell injury, increased vascular permeability, and the activation of neutrophils and cytokines. Niosomes are nanocarriers and an essential part of drug delivery systems. We aimed to investigate the effects of myrtenol's inhaled and intraperitoneal niosomal form, compared to its simple form, on lung ischemia reperfusion injury (LIRI). MATERIAL AND METHOD: Wistar rats were divided into ten groups. Simple and niosomal forms of myrtenol were inhaled or intraperitoneally injected daily for one week prior to LIRI. We evaluated oxidative stress, apoptotic, and inflammatory indices, nitric oxide, inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS) and histopathological indices. RESULTS: Pretreatment with simple and niosomal forms of myrtenol significantly inhibited the indices of pulmonary edema, pro-inflammatory cytokines and proteins, oxidant agents, nitric oxide, iNOS, apoptotic proteins, congestion of capillaries, neutrophil infiltration, and bleeding in the alveoli. Furthermore, myrtenol increased anti-inflammatory cytokines, anti-oxidants agents, eNOS, anti-apoptotic proteins and the survival time of animals. The niosomal form of myrtenol showed a more ameliorative effect than its simple form. CONCLUSION: The results showed the superior protective effect of the inhalation of myrtenol niosomal form against LIRI compared to its simple form and systemic use.

Hematocytological Clues of Peripheral Blood in Different Clinical Presentations of COVID-19.

Background: To gain insight into the pathogenesis and clinical course of COVID-19 from a historical perspective, we reviewed paraclinical diagnostic tools of this disease and prioritized the patients with a more severe form of disease admitted to intensive care units (ICUs). The objective was to better predict the course and severity of the disease by collecting more paraclinical data, specifically by examining the relationship between hematological findings and cytological variation of blood neutrophils and monocytes. Methods: This retrospective study was conducted on 112 patients with confirmed COVID-19 admitted to Imam Hossein Hospital (Tehran, Iran) from August to September 2020. Peripheral blood smears of these patients were differentiated according to several cytological variations of neutrophils and monocytes, and the correlation to the severity of the disease was specified. Results: The mean percentages of degenerated monocytes, degenerated granulocytes, and spiky biky neutrophils were significantly different among critical and non-critical patients (P<0.05). Degenerated monocytes and granulocytes were higher in critical patients as opposed to spiky biky neutrophils, which were higher among non-critical ones. Comparing the peripheral blood smears of COVID-19 patients (regarding pulmonary involvement in chest computed tomography [CT] scans [subtle, mild, moderate, and severe groups]), the twisted form of neutrophils was significantly higher in the subtle group than in the mild and moderate groups (P=0.003). Conclusion: Different cytological morphologies of neutrophils and monocytes, including degenerated monocytes, degenerated granulocytes, and spiky biky and twisted neutrophils, could help to predict the course and severity of the disease.

Advanced Sinonasal Malignant Melanoma; A Case Report.

Malignant melanoma of the sinonasal area is a rare tumor that arises from melanocytes in the nasal mucosa and is more aggressive than the cutaneous type with a poor prognosis. We report a 60-year-old female with the initial chief complaint of nasal cavity fullness, continuous epistaxis, and nasal bone deformity in the past two months. In a primary examination, a black mass was found, and in an excisional biopsy, the pathologist reported sinonasal malignant melanoma, which was confirmed after IHC staining. In spindle cell tumors of the head and neck area, we should be aware of mucosal malignant melanoma as a differential diagnosis.

Evaluation of Laboratory Findings of Patients with Coronavirus Disease 2019 in Kerman, Iran.

Background & Objective: Since December 2019 in Wuhan, China there is a new form of pneumonia and after expansion in other countries, World Health Organization (WHO) called it Coronavirus Disease 2019 (COVID-19). Since the clinical laboratory findings have played an important role in the progression of the disease, this study aimed to evaluate the laboratory findings in COVID-19 patients (before vaccination). Methods: In this case-control study that was conducted from February to August 2020; the laboratory test status in 101 positive COVID-19 patients was evaluated and compared with 101 healthy individuals. Results: The results of our study showed that 21% of patients had low WBC, 24.75% low RBC, 37.62%, low Hb, 18.81% with low HCT, 29.7%, low Plt, 41.58% had High PT, 71.29% high CRP, 17.82% high urea, 11.88% high CR, 15.84% high LDH, 10.89% low sodium, 14.75% low potassium (K). The quantitative examination of blood factors showed that lymph%, mixed%, PLT, HCT, Hb, and RBC were higher in the control group than in the case group. While Neu%, WBC, PTT, CRP, UREA, LDH, K in the patient group were higher than in the control group. Conclusion: According to the results of the study, it can be concluded that in the clinical treatment of COVID-19 patients, much attention should be paid to the laboratory indicators to identify and intervene early in critically ill patients.

Exploring mesoporous silica nanoparticles as oral insulin carriers: In-silico and in vivo evaluation.

The advancements in nanoscience have brought attention to the potential of utilizing nanoparticles as carriers for oral insulin administration. This study aims to investigate the effectiveness of synthesized polymeric mesoporous silica nanoparticles (MSN) as carriers for oral insulin and their interactions with insulin and IR through in-silico docking. Diabetic rats were treated with various MSN samples, including pure MSN, Amin-grafted MSN/PEG/Insulin (AMPI), Al-grafted MSN/PEG/Insulin (AlMPI), Zinc-grafted MSN/PEG/Insulin (ZNPI), and Co-grafted MSN/PEG/Insulin (CMPI). The nanocomposites were synthesized using a hybrid organic-inorganic method involving MSNs, graphene oxide, and insulin. Characterization of the nanocomposites was conducted using X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, and scanning electron microscopy (SEM). In vivo tests included the examination of blood glucose levels and histopathological parameters of the liver and pancreas in type 1 diabetic rats. The MSN family demonstrated a significant reduction in blood glucose levels compared to the diabetic control group (p < 0.001). The synthesized nanocomposites exhibited safety, non-toxicity, fast operation, self-repairing pancreas, cost-effectiveness, and high efficiency in the oral insulin delivery system. In the in-silico study, Zn-grafted MSN, Co-grafted MSN, and Al-grafted MSN were selected. Docking results revealed strong interactions between MSN compounds and insulin and IR, characterized by the formation of hydrogen bonds and high binding energy. Notably, Co-grafted MSN showed the highest docking scores of -308.171 kcal/mol and -337.608 kcal/mol to insulin and IR, respectively. These findings demonstrate the potential of polymeric MSN as effective carriers for oral insulin, offering promising prospects for diabetes treatment.

Rhinocerebral Mucormycosis Following COVID-19 Infection in Iran.

Background & Objective: Mucormycosis (also called black fungus) is an opportunistic serious fungal infection caused by mucormycetes. It can occur in diabetes mellitus patients and other immunosuppressive conditions with recent predisposing factors such as maxillofacial surgery and corticosteroid usage. Methods: In this study, 14 patients were referred to the otorhinolaryngology or ophthalmology ward of Shafa Hospital (Kerman, Iran) with primary symptoms of nasal fullness and facial nerve dysfunction; they were admitted to the hospital to rule out the fungal infection. An endoscopic biopsy was taken from facial sinuses or orbit, and a microscopic evaluation was performed using hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining methods to rule out mucormycosis. Results: In the histopathological examination, broad-based nonseptate branching fungal hyphae were found in nasal sinuses through the endoscopic biopsy. Most of the patients had diabetes mellitus with a primary symptom of facial nerve palsy; also, most of them received corticosteroids (intravenous [IV] or intramuscular [IM] injection). All patients have recently been infected with COVID-19 (less than 1 month ago). Conclusion: COVID-19 infection might be a predisposing factor for many opportunistic infections, such as fungal elements); thus, the physician should be aware of the dosage and duration of corticosteroid therapy to prevent the development of these infections.

Evaluation of hematological parameters alterations in different waves of COVID-19 pandemic: A cross-sectional study.

BACKGROUND: The occurrence of variations in routine hematological parameters is closely associated with disease progression, the development of severe illness, and the mortality rate among COVID-19 patients. This study aimed to investigate hematological parameters in COVID-19 hospitalized patients from the 1st to the 5th waves of the current pandemic. METHODS: This cross-sectional study included a total of 1501 hospitalized patients with laboratory-confirmed COVID-19 based on WHO criteria, who were admitted to Shahid Sadoughi Hospital (SSH) in Yazd, Iran, from February 2020 to September 2021. Throughout, we encountered five COVID-19 surge waves. In each wave, we randomly selected approximately 300 patients and categorized them based on infection severity during their hospitalization, including partial recovery, full recovery, and death. Finally, hematological parameters were compared based on age, gender, pandemic waves, and outcomes using the Mann-Whitney U and Kruskal-Wallis tests. RESULTS: The mean age of patients (n = 1501) was 61.1±21.88, with 816 (54.3%) of them being men. The highest mortality in this study was related to the third wave of COVID-19 with 21.3%. There was a significant difference in all of the hematological parameters, except PDW, PLT, and RDW-CV, among pandemic waves of COVID-19 in our population. The highest rise in the levels of MCV and RDW-CV occurred in the 1st wave, in the 2nd wave for lymphocyte count, MCHC, PLT count, and RDW-SD, in the 3rd wave for WBC, RBC, neutrophil count, MCH, and PDW, and in the 4th wave for Hb, Hct, and ESR (p < 0.01). The median level of Hct, Hb, RBC, and ESR parameters were significantly higher, while the mean level of lymphocyte and were lower in men than in women (p < 0.001). Also, the mean neutrophil in deceased patients significantly was higher than in those with full recovered or partial recovery (p < 0.001). CONCLUSION: The findings of our study unveiled notable variations in hematological parameters across different pandemic waves, gender, and clinical outcomes. These findings indicate that the behavior of different strains of the COVID-19 may differ across various stages of the pandemic.

Sodium hydrogen sulfide may not protect the kidney against ischemia/reperfusion damage in male and female rats.

Background and purpose: Renal ischemia/reperfusion (IR) injury is a pathologic phenomenon that caused to increase risk of mortality. The main objective of this study was to investigate the effect of sodium hydrogen sulfide (NaHS) on renal IR injury in male and female rats. Experimental approach: Fifty-eight male and female rats were randomized into 4 groups of control, sham, IR, and IR + NaHS. The IR was performed by 45 min of ischemia by vessel clamping followed by 24 h reperfusion. The NaHS (100 µmol/kg) treatment was applied 10 min prior to IR. Finally, after 24 h of reperfusion, the measurements were performed. Findings/Results: The serum levels of blood urea nitrogen, creatinine, tissue level of malondialdehyde, and kidney tissue damage score (KTDS) were increased by IR. Urine volume, creatinine, and urea clearances decreased by IR. NaHS administration improved some parameters in males but exacerbated KTDS and serum markers related to renal function. Conclusions and implications: Our data demonstrated that NaHS didn't protect female rats against renal IR injury. In males, it has null effects or just a few protective effects via antioxidant activity.

Design of ion channel blocking, toxin-like Kunitz inhibitor peptides from the tapeworm, Echinococcus granulosus, with potential anti-cancer activity.

Over-expression of K+ channels has been reported in human cancers and is associated with the poor prognosis of several malignancies. EAG1, a particular potassium ion channel, is widely expressed in the brain but poorly expressed in other normal tissues. Kunitz proteins are dominant in metazoan including the dog tapeworm, Echinococcus granulosus. Using computational analyses on one A-type potassium channel, EAG1, and in vitro cellular methods, including major cancer cell biomarkers expression, immunocytochemistry and whole-cell patch clamp, we demonstrated the anti-tumor activity of three synthetic small peptides derived from E. granulosus Kunitz4 protease inhibitors. Experiments showed induced significant apoptosis and inhibition of proliferation in both cancer cell lines via disruption in cell-cycle transition from the G0/G1 to S phase. Western blotting showed that the levels of cell cycle-related proteins including P27 and P53 were altered upon kunitz4-a and kunitz4-c treatment. Patch clamp analysis demonstrated a significant increase in spontaneous firing frequency in Purkinje neurons, and exposure to kunitz4-c was associated with an increase in the number of rebound action potentials after hyperpolarized current. This noteworthy component in nature could act as an ion channel blocker and is a potential candidate for cancer chemotherapy based on potassium channel blockage.

A case report of transmural rectosigmoid ischemia in an elderly patient.

INTRODUCTION AND IMPORTANCE: While acute colonic ischemia is frequently observed in the elderly, rectal ischemia is a rare occurrence. We presented a case of transmural rectosigmoid ischemia in a patient who had not undergone any significant interventions and had no underlying diseases. Conservative treatment methods were unsuccessful, and surgical resection was necessary to prevent the development of gangrene or sepsis. CASE PRESENTATION: Upon arrival at our health center, a 69-year-old man reported experiencing left lower quadrant pain and rectorrhagia. The CT scan revealed thickening in the sigmoid and rectum. Subsequent colonoscopy revealed circumferential ulcers, severe edema, erythema, discoloration, and ulcerative mucosa in both the rectum and sigmoid. Due to persistent severe rectorrhagia and worsening pathologic parameters, another colonoscopy was performed three days later. CLINICAL DISCUSSION: Initially, conservative treatments were administered, but as the tenderness worsened, surgical exploration of the abdomen was necessary. During the procedure, a large ischemia from the sigmoid to the rectal dentate line was observed, and the lesion was resected. A stapler was then inserted into the rectum, followed by the use of the Hartman pouch method to deviate the tract. Finally, colectomy, sigmoidectomy, and rectal resection were performed. CONCLUSION: Due to the worsening pathological condition of our patient, surgical resection was necessary. It is important to note that rectosigmoid ischemia, although rare, can develop without a known underlying cause. Therefore, it is crucial to consider and evaluate potential causes beyond the most common ones. Furthermore, any pain or rectorragia should be assessed immediately.

Langerhans cell histiocytosis presented as bilateral otitis media with effusion, a rare case report.

Background: Langerhans cell histiocytosis (LCH) or histiocytosis X is considered as a rare disease that may have effect on multiple organs. The initial presentation of LCH is varied. The signs and symptoms of otologic histiocytosis can be the same as the acute or chronic infectious ear diseases. Definitive diagnosis of LCH is confirmed by biopsy and immunohistochemically staining of S-100 protein and CD1a antigen. Chemotherapy is the main mode of treatment. Case presentation: In this report, we explained the clinical manifestation, diagnosis and treatment of a case of 15 month-old girl with diagnosed of LCH that initially presented with otitis media with effusion (OME). Conclusion: LCH is a rare disease that presented with variable sign and symptoms and have an effect on multiple organs. LCH should be regarded in cases with recurrent ear infection without response to medical treatments. Moreover, biopsy with IHC is the gold standard of diagnosis and chemotherapy is the main form of treatment.

Protective effects of calorie restriction and 17-ß estradiol on cardiac hypertrophy in ovariectomized obese rats.

Obesity and menopause lead to cardiovascular diseases. Calorie restriction (CR) can modulate estrogen deficiency and obesity-related cardiovascular diseases. The protective effects of CR and estradiol on cardiac hypertrophy in ovariectomized obese rats were explored in this study. The adult female Wistar rats were divided into sham and ovariectomized (OVX) groups that received a high-fat diet (60% HFD) or standard diet (SD) or 30% CR for 16 weeks, and then, 1mg/kg E2 (17-ß estradiol) was injected intraperitoneally every 4 days for four weeks in OVX-rats. Hemodynamic parameters were evaluated before and after each diet. Heart tissues were collected for biochemical, histological, and molecular analysis. HFD consumption led to weight gain in sham and OVX rats. In contrast, CR and E2 led to body weight loss in these animals. Also, heart weight (HW), heart weight/body weight (HW/BW) ratio, and left ventricular weight (LVW) were enhanced in OVX rats that received SD and HFD. E2 reduced these indexes in both diet conditions but reduction effects of CR were seen only in HFD groups. HFD and SD feeding increased hemodynamic parameters, ANP (atrial natriuretic peptide) mRNA expression, and TGF-ß1(transforming growth factor-beta 1) protein level in the OVX animals, while CR and E2 reduced these factors. Cardiomyocyte diameter and hydroxyproline content were increased in the OVX-HFD groups. Nevertheless, CR and E2 decreased these indicators. The results showed that CR and E2 treatment reduced obesity-induced-cardiac hypertrophy in ovariectomized groups (20% and 24% respectively). CR appears to have almost as reducing effects as estrogen therapy on cardiac hypertrophy. The findings suggest that CR can be considered a therapeutic candidate for postmenopausal cardiovascular disease.

Adverse effects of methamphetamine on vital organs of male rats: Histopathological and immunohistochemical investigations.

Objectives: Methamphetamine (named crystal, ice, and crank), is a strong psychostimulant drug with addictive and neurotoxic properties. It is absorbed by various organs and induces tissue damage in abusers. Most METH studies have focused on the central nervous system and its effects on other organs have been neglected. Experimental investigations of animal models are used to provide significant additional information. We have studied the histopathological effects of methamphetamine in the brains, hearts, livers, testes, and kidneys of rats. Materials and Methods: Methamphetamine (0.5 mg/kg) was administered subcutaneously for 21 days. Immunohistochemistry was carried out with markers including glial fibrillary acidic protein (GFAP) for reactive astrocytes, vimentin as an intermediate filament in different cells, and CD45 marker for the detection of reactive microglia in the brain. Also, some samples were taken from livers, kidneys, hearts, and testes. Results: Degenerative changes and necrosis were the most common histopathological effects in the liver, kidneys, heart, testes, and brains of rats treated with methamphetamine. Immunohistochemical analyses by vimentin and GFAP markers revealed reactive microglia and astrocytes with the appearance of swollen cell bodies and also short, thickened, and irregular processes. Moreover, the number of CD45-positive cells was higher in this group. Reactive cells were more noticeable in the peduncles and subcortical white matter of the cerebellum. Conclusion: Our results showed the toxic effects of methamphetamine on the vital organs and induction of neurotoxicity, cardiomyopathy, renal damage, and infertility in male rats. We could not attribute observed hepatic changes to METH and further evaluation is needed.

Beneficial effects of berberine against pulmonary complications of experimental pulmonary arterial hypertension in rats and some relevant mechanisms.

Pulmonary arterial hypertension (PAH) is a severe disease that leads to pulmonary vascular remodeling characterized by a rise in pulmonary vascular resistance and pressure. We assessed the effects of an herbal compound, berberine (BB), and some related mechanisms on PAH in rats. Male Wistar rats were assigned to seven groups: control, monocrotaline (MCT), MCT+vehicle, and MCT+BB (with doses of 10, 20, 30, and 40 mg/kg) groups. Three weeks after induction of PAH by MCT, treatment groups received daily intraperitoneal injections of vehicle or BB for 3 weeks. On Day 43, the right ventricular systolic pressure (RVSP, as an index of pulmonary arterial pressure) and the ratio of RV to LV+septum weight (as RV hypertrophy index, right ventricle hypertrophy [RHVI]) were measured. Inflammatory and oxidative stress indices and histopathology of the lungs were also assessed. RVSP (89.4 ± 8.2 vs. 23 ± 3.3), RVHI (0.63 ± 0.08 vs. 0.26 ± 0.04), and lung inflammatory cytokines TNF-α (2.03 ± 0.25 vs. 1.21 ± 0.3) and IL-6 (8.8 ± 0.59 vs. 6.3 ± 0.95) significantly increased in the MCT group compared to the control group. MCT also raised the level of Malondialdehyde (0.11 ± 0.01 vs. 0.09 ± 0.01) and diminished total antioxidant capacity (6.5 ± 0.51 vs. 8.3 ± 0.62), the activity of superoxide dismutase (1.19 ± 0.22 vs. 1.93 ± 0.2), glutathione peroxidase (0.02 ± 0.002 vs. 0.03 ± 0.005), catalase (2.1 ± 0.29 vs. 2.8 ± 0.20) and Bax/Bcl-2 ratio (0.41 ± 0.07 vs. 0.61 ± 0.09) in the lungs. Treatment with BB significantly recovered all of these alterations. BB ameliorated pulmonary vascular remodeling by decreasing inflammation and fibrosis and increasing apoptosis and antioxidant/oxidant balance. Therefore, this herbal derivative may be considered a therapeutic goal against PAH.