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.

Characterization of the first microRNA in human CDH1 that affects cell cycle and apoptosis and indicates breast cancers progression.

The E-cadherin protein (Cadherin 1, gene: CDH1), a master regulator of the human epithelial homeostasis, contributes to the epithelial-mesenchymal transition (EMT) which confers cell migratory features to the cells. The EMT is central to many pathophysiological changes in cancer. Therefore, a better understanding of this regulatory scenario is beneficial for therapeutic regiments. The CDH1 gene is approximately 100 kbp long and consists of 16 exons with a relatively large second intron. Since none microRNA (miRNA) has been identified in CDH1 up to now we screened the CDH1 gene for promising miRNA hairpin structures in silico. Out of the 27 hairpin structures we identified, one stable RNA fold with a promising sequence motive was selected for experimental verification. The exogenous validation of the hairpin sequence was performed by transfection of HEK293T cells and the mature miRNA sequences could be verified by quantitative polymerase chain reaction. The endogenous expression of the mature miRNA provisionally named CDH1-i2-miR-1 could be confirmed in two normal (HEK293T, HUVEK) and five cancer cell lines (MCF7, MDA-MB-231, SW480, HT-29, A549). The functional characterization by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed a suppression of HEK293T cell proliferation. A flow cytometry-based approach showed the ability of CDH1-i2-miR-1 to arrest transfected cells on a G2/M state while annexin staining exemplified an apoptotic effect. BAX and PTEN expression levels were affected following the overexpression with the new miRNA. The in vivo expression level was assessed in 35 breast tumor tissues and their paired nonmalignant marginal part. A fourfold downregulation in the tumor specimens compared to their marginal controls could be observed. It can be concluded that the sequence of the hub gene CDH1 harbors at least one miRNA but eventually even more relevant for the pathophysiology of breast cancer.

The brain neuropeptides and STAT3 mediate the inhibitory effect of 17-ß Estradiol on central leptin resistance in young but not aged female high-fat diet mice.

Aging and menopause effect on body composition and energy balance. Estrogen (E2) plays an important role in body's metabolism. The aim of the present study was to determine changes in leptin function in young intact and ovariectomized (OVX) animals in comparison to the aged animals treated with E2. Young (Intact and OVX 4 months) and aged (19-21 months) female mice were fed High-fat diet (HFD) for 12 weeks and, then they were divided into eight groups including: Intact + OIL, Intact + E2, Intact + Pair body weight (PBW), OVX + OIL, OVX + E2, OVX + PBW, Aged + OIL, and Aged + E2. E2 was administered subcutaneously every four days for four weeks. Responsiveness to leptin was assessed by measuring energy balance components. Results showed that eating HFD increased weight and calorie consumption in young mice, and chronic treatment with E2 decreased both these variables in young animals. E2 only improved the sensitivity to leptin in young animals. Treatment with E2 resulted in increased α-MSH neuropeptide, reduced NPY and AgRP neuropeptides in the brain, and decreased serum leptin in the young animals. Also, treatment with E2 increased the expression of p-STAT3 molecular level in the hypothalamic arcuate nucleus (ARC) in the young animals. Our results indicated that response to E2 depended on age and E2 protects young HFD fed mice from obesity and improves leptin sensitivity.

An intelligent DNA nanorobot for detection of MiRNAs cancer biomarkers using molecular programming to fabricate a logic-responsive hybrid nanostructure.

Herein, we designed a DNA framework-based intelligent nanorobot using toehold-mediated strand displacement reaction-based molecular programming and logic gate operation for the selective and synchronous detection of miR21 and miR125b, which are known as significant cancer biomarkers. Moreover, to investigate the applicability of our design, DNA nanorobots were implemented as capping agents onto the pores of MSNs. These agents can develop a logic-responsive hybrid nanostructure capable of specific drug release in the presence of both targets. The prosperous synthesis steps were verified by FTIR, XRD, BET, UV-visible, FESEM-EDX mapping, and HRTEM analyses. Finally, the proper release of the drug in the presence of both target microRNAs was studied. This Hybrid DNA Nanostructure was designed with the possibility to respond to any target oligonucleotides with 22 nucleotides length.

Immunopathology of anthroponotic cutaneous leishmaniasis and incidental diagnostic tool of metastatic granuloma: A case-control study.

BACKGROUND: Cutaneous leishmaniasis (CL) is a neglected disease with important public health concerns in many parts of the world including Iran. OBJECTIVES: We aimed to explore the histological changes and immunohistochemical quantification of inflammatory cells and their role in the immunopathology of acute, chronic non-lupoid, and chronic lupoid skin lesions in anthroponotic CL (ACL). METHODS: In this study, skin biopsies of 53 patients with ACL were taken. Samples were studied by light microscopy and immunohistochemistry to quantify the immune and inflammatory cells. RESULTS: Of the 53 skin lesions, 38 were acute, nine chronic non-lupoid and six chronic lupoid. CD68+ macrophages were the most common cells. CD3+ T-lymphocytes were present as diffuse and focal dermal infiltrates and CD8+ cytotoxic T-lymphocytes were the dominant lymphocyte type, constituting more than 50% of the lymphocyte population. CD4+ T-lymphocytes in chronic non-lupoid (10.57 ± 2.37%) and chronic lupoid (14.40 ± 1.28%) lesions were more than those observed in the acute form (8.61 ± 1.31%), but the differences were not statistically significant. CD20+ B-lymphocytes constituted a small percentage of inflammatory cell infiltrates. CD1a + Langerhans cells showed progressively higher percentages from acute to chronic non-lupoid to chronic lupoid lesions. The differences were statistically significant (P < 0.05) between acute and chronic lupoid lesions. CD68+ macrophages were the most common cells and CD8+ T lymphocytes remained the predominant T-lymphocytes in acute, chronic non-lupoid, and chronic lupoid lesions, suggesting their central role in the pathogenesis and possible healing of CL. CONCLUSION: Focusing on the deep dermis, periadnexal and/or peripheral margins or even papillary tip of inflammatory sites of sandfly bites, we sometimes find granuloma inside lymphatic vessels (lymphangiectatic metastatic granuloma) or even infected macrophages with engulfed Leishman bodies faraway. Knowledge of the histopathological and immunohistochemical findings for various forms of ACL is essential in improving clinical and medical strategies and crucial for proper prophylactic and therapeutic plans.

Vascular apoptosis associated with meglumine antimoniate: In vivo investigation of a chick embryo model.

The vasculo-toxic effect of meglumine antimoniate (MA) was confirmed in our previous investigation. The current study investigates the association of this effect with altered VEGF-A and VEGF-R2 expression. Additional mechanisms by which MA causes vascular toxicity are not clearly understood. We hypothesized that MA may alter normal expression of apoptotic genes and cause vascular toxicity. The current investigation was designed to address this issue using a chick embryo model. Fertile chicken eggs were treated with MA and the extra-embryonic membrane (EEM) vasculature was evaluated by morphometric, molecular and immunohistochemistry assays. The results showed that MA not only altered apoptotic gene expression, but that this alteration may disturb the normal development of the vascular network and cause embryo malformation. The relative expression level of the CASP3, CASP7, CASP9, APAF1, AIF1 and TP53 genes increased in drug-exposed EEMs. In addition, IHC assay confirmed the low expression BCL2 and increased expression of Bax, which are associated with a high rate of apoptosis. We suggest that induction of an apoptotic signaling pathway can lead to vascular defects during embryo development and the consecutive cascade of events can lead to the embryo malformation.

The effect of interleukins 27 and 35 and their role on mediating the action of insulin Like Growth Factor -1 on the inflammation and blood flow of chronically inflamed rat knee joint.

INTRODUCTION: Previous studies have shown that some cytokines mediate the effect of IGF-1 on inflammation and also association between IGF-1 and vascular endothelial dysfunction. Due to the discrepancies in the inflammatory and anti-inflammatory roles of IL-27 and IL-35, the effects of these cytokines and their IGF-1-mediating role were investigated regarding chronic joint inflammation and synovial blood flow. METHOD: Male rats were divided into two main groups of histopathology (n=80) and blood flow (n=72). These were further divided into ten subgroups of control, vehicle, IGF-1, IL-27, IL-35, their antagonists, IGF-1+IL-27 antagonist, and IGF-1+IL-35 antagonist. Inflammation was induced by intra-articular injection of complete Freund adjuvant. Two weeks later (in order to induce chronic inflammation), vehicle or drugs were injected into the joint space every other day until day 28, on which inflammatory indices were assessed histopathologically. In the second subgroups, vehicle or drugs were administered by super-fusion on day 28 and their effects on the joint blood flow (JBF, laser Doppler perfusion method) and the systemic blood pressure were assessed. RESULTS: Endogenous IL-27 and IL-35 had inflammatory roles and IGF-1 had no effect. IL-27 and IL-35 antagonists had the highest anti-inflammatory and anti-angiogenesis effects and these effects were inhibited by IGF-1. Total inflammation score was 4.5 ± 0.42, 3.50 ± 0.5, 2.25 ± 0.45 and 1.50 ± 0.42 for vehicle, IGF-1 antagonist, IL-27 antagonist and IL-35 antagonist respectively. A significant increase was induced in JBF by IGF-1 antagonist and combination of IGF-1+IL-35 antagonist. CONCLUSION: IL-27 and IL-35 antagonists may be suitable goals for the treatment of chronic joint inflammation while their anti-inflammatory effects are not exerted via the changes in JBF.

Coadministration of Atorvastatin and Amiodarone Increases the Risk of Pulmonary Fibrosis in Rats.

OBJECTIVE: The purpose of this study was to evaluate the effect of atorvastatin administration on amiodarone-induced pulmonary fibrosis in rats. MATERIALS AND METHODS: Thirty-six male Wistar rats were randomly divided into 4 groups. The control group (CTL) received distilled water (0.3 ml intratracheally on days 0 and 2 and 0.5 ml orally from day 0 for 3 weeks). The atorvastatin group (AT), in addition to intratracheal distilled water, received 1 mg/kg of atorvastatin orally from day 0 for 3 weeks. The amiodarone group (AMI) received 2 intratracheal instillations of amiodarone (6.25 mg/kg in 0.3 ml of water) on days 0 and 2 and 0.5 ml of distilled water (like the CTL). The amiodarone plus atorvastatin group (AMI + AT) received both these drugs (same doses and methods as for the AMI and AT). After 28 days, the rate of lung fibrosis was estimated according to pathological criteria of lung sections and measurements of hydroxyproline in pieces of left lung tissue. RESULTS: The lung hydroxyproline content was higher in the treated groups (CTL: 0.35 ± 0.017, AT: 0.38 ± 0.012, AMI: 0.375 ± 0.018 and AMI + AT: 0.38 ± 0.012 unit/mg protein), but did not reach significance when compared with the CTL (p = 0.56). Amiodarone administration significantly increased the score of pulmonary fibrosis (0.5) in comparison with the AT (0.125) and CTL (0) (p < 0.5). The combination of amiodarone and atorvastatin exacerbated the pulmonary fibrosis (1.5; p < 0.01) compared to the AMI (0.5; p < 0.001), AT (0.125) and CTL (0). CONCLUSION: In this study, the concomitant administration of amiodarone and atorvastatin increased pulmonary fibrosis in rats.

The effects of Melissa officinalis (lemon balm) pretreatment on the resistance of the heart to myocardial injury.

CONTEXT: The antihyperlipidemic, antiarrhythmic, neuroprotective and hepatoprotective effects of Melissa officinalis L. (Lamiaceae) have been reported. However, no study has examined its effects on the resistance of the heart to stressful conditions. OBJECTIVE: The objective of this study is to evaluate the effects of aqueous extract of M. officinalis aerial parts on Wistar rat heart with/without cardiac injury. MATERIALS AND METHODS: Animals were grouped as control, isoproterenol (ISO), M. officinalis without (M50, M100, and M200) and with isoproterenol (M50 + ISO, M100 + ISO, and M200 + ISO). The aqueous extract of M. officinalis was orally administered at dosages of 50, 100, and 200 mg/kg/d, respectively, for 7 consecutive days. On the 6th and 7th day, ISO, M50 + ISO, M100 + ISO, and M200 + ISO groups received 85 mg/kg of isoproterenol for myocardial injury induction. On day 8, hemodynamic parameters were recorded and samplings were done. RESULTS: The extract (50, 100, and 200 mg/kg) significantly reduced the heart rate (264 ± 5, 259 ± 5 and 281 ± 3 versus 377 ± 13 in control group, p < 0.01). Blood pressure was significantly decreased in M50 + ISO (75 ± 5) versus M50 (110 ± 6) and M100 + ISO (72 ± 6) versus M100 (105 ± 5 mmHg, p < 0.01). The malondialdehyde levels of the injured hearts were lower in M50 + ISO and M100 + ISO groups than in the ISO group (p < 0.05). Serum cardiac troponin I was higher in the M200 + ISO group (5.1 ± 1.7) than in the ISO group (2.7 ± 0.7 ng/ml, p < 0.05). CONCLUSION: The lower dose of extract, by improving the balance of the redox system and by reducing the heart rate, may increase the heart resistance to injury. However, the higher doses of extract may intensify the injury of ischemic heart.

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.

Diagnostic Value of Dermoscopic Structures in Predicting Superficial Basal Cell Carcinoma in the Skin of Color.

Background: Basal cell carcinoma (BCC) manifests different dermoscopic patterns in individuals with dark skin complexion compared to those with fair skin types. This study aimed to investigate the diagnostic utility of dermoscopy in discerning superficial BCC from other types of BCC, specifically in patients with dark skin complexion. Materials and Methods: This cross-sectional study focuses on patients diagnosed with BCC who were referred for skin biopsy between July 2020 and September 2022. Initially, the demographic characteristics of patients, clinical attributes of lesions, and pathological sub-types of BCC were documented. Subsequently, videodermoscopy was employed to capture comprehensive views and dermoscopic images of the lesions. Univariate logistic regression analysis was then utilized to assess the reliability of dermoscopic structures in distinguishing superficial BCC from other BCC types. Last, the study evaluated the sensitivity, specificity, positive predictive value, and negative predictive value of dermoscopy in the differentiation of superficial BCC from other BCC sub-types. Results: The study enrolled 49 patients diagnosed with BCC, with a mean age of 66.22 ± 10.41 years. The most prevalent pathological sub-type observed was nodular (53.1%). Dermoscopy exhibited a higher specificity compared to the naked eye in the differentiation of superficial BCC from other types (55% vs. 35%, respectively). Univariate analysis revealed a significant association between spoke-wheel structures and superficial BCC (P = 0.02, odds ratio = 7.2, 95% confidence interval = 1.35-38.32). Conclusion: Dermoscopy exhibited superior specificity compared to the naked eye in differentiating superficial BCC from other BCC types. Notably, the spoke-wheel structure demonstrated the most robust correlation with superficial BCC.

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.

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.

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.

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.

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.

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.

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.

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.