First Iranian guidelines for the diagnosis, management, and treatment of hyperlipidemia in adults.

This guideline is the first Iranian guideline developed for the diagnosis, management, and treatment of hyperlipidemia in adults. The members of the guideline developing group (GDG) selected 9 relevant clinical questions and provided recommendations or suggestions to answer them based on the latest scientific evidence. Recommendations include the low-density lipoprotein cholesterol (LDL-C) threshold for starting drug treatment in adults lacking comorbidities was determined to be over 190 mg/dL and the triglyceride (TG) threshold had to be >500 mg/dl. In addition to perform fasting lipid profile tests at the beginning and continuation of treatment, while it was suggested to perform cardiovascular diseases (CVDs) risk assessment using valid Iranian models. Some recommendations were also provided on lifestyle modification as the first therapeutic intervention. Statins were recommended as the first line of drug treatment to reduce LDL-C, and if its level was high despite the maximum allowed or maximum tolerated drug treatment, combined treatment with ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, or bile acid sequestrants was suggested. In adults with hypertriglyceridemia, pharmacotherapy with statin or fibrate was recommended. The target of drug therapy in adults with increased LDL-C without comorbidities and risk factors was considered an LDL-C level of <130 mg/dl, and in adults with increased TG without comorbidities and risk factors, TG levels of <200 mg/dl. In this guideline, specific recommendations and suggestions were provided for the subgroups of the general population, such as those with CVD, stroke, diabetes, chronic kidney disease, elderly, and women.

Microfluidic-based technologies in cancer liquid biopsy: Unveiling the role of horizontal gene transfer (HGT) materials.

Liquid biopsy includes the isolating and analysis of non-solid biological samples enables us to find new ways for molecular profiling, prognostic assessment, and better therapeutic decision-making in cancer patients. Despite the conventional theory of tumor development, a non-vertical transmission of DNA has been reported among cancer cells and between cancer and normal cells. The phenomenon referred to as horizontal gene transfer (HGT) has the ability to amplify the advancement of tumors by disseminating genes that encode molecules conferring benefits to the survival or metastasis of cancer cells. Currently, common liquid biopsy approaches include the analysis of extracellular vesicles (EVs) and tumor-free DNA (tfDNA) derived from primary tumors and their metastatic sites, which are well-known HGT mediators in cancer cells. Current technological and molecular advances expedited the high-throughput and high-sensitive HGT materials analyses by using new technologies, such as microfluidics in liquid biopsies. This review delves into the convergence of microfluidic-based technologies and the investigation of Horizontal Gene Transfer (HGT) materials in cancer liquid biopsy. The integration of microfluidics offers unprecedented advantages such as high sensitivity, rapid analysis, and the ability to analyze rare cell populations. These attributes are instrumental in detecting and characterizing CTCs, circulating nucleic acids, and EVs, which are carriers of genetic cargo that could potentially undergo HGT. The phenomenon of HGT in cancer has raised intriguing questions about its role in driving genomic diversity and acquired drug resistance. By leveraging microfluidic platforms, researchers have been able to capture and analyze individual cells or genetic material with enhanced precision, shedding light on the potential transfer of genetic material between cancer cells and surrounding stromal cells. Furthermore, the application of microfluidics in single-cell sequencing has enabled the elucidation of the genetic changes associated with HGT events, providing insights into the evolution of tumor genomes. This review also discusses the challenges and opportunities in studying HGT materials using microfluidic-based technologies. In conclusion, microfluidic-based technologies have significantly advanced the field of cancer liquid biopsy, enabling the sensitive and accurate detection of HGT materials. As the understanding of HGT's role in tumor evolution and therapy resistance continues to evolve, the synergistic integration of microfluidics and HGT research promises to provide valuable insights into cancer biology, with potential implications for precision oncology and therapeutic strategies.

The potential interplay between opioid and the toll-like receptor 4 (TLR-4).

CONTEXT: Opioids are available for the management of severe and chronic pain. However, long-term use of high-dose opioids could lead to physiologic tolerance, hyperalgesia, gastrointestinal immobility, addiction, respiratory depression, tumor progression, and inhibition of the immune system. It seems some of these adverse effects of opioids might be induced by TLR-4 signaling. OBJECTIVE: The review aims to investigate the potential interplay between opioids and TLR-4 in CNS, gastrointestinal, cancer, and immune system. METHODS: The search of PubMed, Embase, Scopus, web of sciences, and Google scholar was performed for all relevant studies published. From a total of 513 papers obtained at the initial database search, publications including in silico, in vitro, and in vivo studies were selected for the review. RESULTS: A comprehensive review of studies indicated that using opioids for the reduction of pain might induce adverse effects such as analgesic tolerance, hyperalgesia, cancer progression, and suppression of the immune system. Some studies have indicated these effects may be due to a change in the level of expression and signaling pathway of TLR-4. The generalizability of the results was limited due to the inconsistency of findings. CONCLUSIONS: More studies are needed to clarify TLR-4-mediated opioid effects on the biology or stages of the disease as well as the role of different types of opioids, appropriate dosage, and exposure in various contexts. Designing the drug candidate and doing many formulation studies for different diseases and various stages of disease could be associated with effective treatment and pain management.

Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice.

BACKGROUND: Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice. METHODS: Mice melanoma cells (B16F10) were cultured with morphine (0.1, 1 and 10 µM) for 24 h. In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). In in-vivo model, B16F10 cells were subcutaneously injected to C57BL/6 mice, and morphine was administrated in three different treatment protocols after developing palpable tumors (acute treatment, chronic daily injections, escalating doses of morphine). In another set of experiments, B16F10 cells were pretreated with LPS (5 µg/ml) 24 h before injection into mice. Control group received normal saline. We measured cell proliferation, the expression level of Tlr4, Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (Nf-κb1) genes, TLR4 protein expression, and tumor volume. RESULTS: Chronic, acute, and escalating doses of morphine increased tumor. Morphine increased the expression of Tlr4 and Nf-κb1 regardless of the treatment protocol used. CONCLUSION: Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.

Antimicrobial activity and wound healing effect of a novel natural ointment: an in vitro and in vivo study.

Infection and pathological disorders, such as cellular disorders, ischaemia, neuropathy and angiogenesis, are considered the most critical factors which cause a delay in the wound healing process in patients with diabetes. This study aimed to investigate the effect of an ointment based on ostrich oil containing honey, beeswax, and ethanolic extracts of Nigella sativa, propolis and Cassia angustifolia on the wound healing process of diabetic rats. Gas chromatography/mass spectrometry analysis showed caffeic acid and pinostrobin chalcone molecules present in propolis, giving antibacterial and antifungal properties to the compound. The antibacterial assessment showed the ointment had remarkable antibacterial activity against Staphylococcus aureus (8.6±0.28mm), Escherichia coli (9.4±0.31mm), Acinetobacter baumannii (7.2±0.23mm) and Pseudomonas aeruginosa (13.9±0.42mm). In vivo results showed the ointment significantly accelerated wound healing and increased collagen deposition compared with the control (p<0.05). Histopathology evaluation also showed hair follicles, sebaceous glands and vessels in the group that used the ointment. These results proved successful and diabetic wound healing was rapid. Therefore, it could be concluded that the fabricated ointment could be a suitable candidate for wound healing.

Shared Lifestyle-Related Risk Factors of Cardiovascular Disease and Cancer: Evidence for Joint Prevention.

Cardiovascular disease (CVD) and cancer are leading causes of mortality and morbidity worldwide and are the major focus of the World Health Organization's joint prevention programs. While, diverse diseases, CVD and cancer, have many similarities. These include common lifestyle-related risk factors and shared environmental, metabolic, cellular, inflammatory, and genetic pathways. In this review, we will discuss the shared lifestyle-related and environmental risk factors central to both diseases and how the strategies commonly used to prevent atherosclerotic vascular disease can be applied to cancer prevention.

Effect of serum magnesium levels on outcomes of patients hospitalized with COVID-19.

BACKGROUND:  The coronavirus disease 2019 (COVID-19) causes acute respiratory illness and multi-organ failure. The critical roles of magnesium in human health suggest that it could have an active role in the prevention and treatment of COVID-19. We measured magnesium levels in hospitalized COVID-19 patients concerning disease progression and mortality. MATERIALS AND METHODS:  This study was conducted in 2321 hospitalized COVID-19 patients. Clinical characteristics from each patient were recorded, and blood samples were collected from all patients upon their first admission to the hospital to determine serum magnesium levels. Patients were divided into two groups based on discharge or death. The effects of magnesium on death, severity, and hospitalization duration were estimated by crude and adjusted odds ratio using Stata Crop (version 12) software. RESULTS:  Mean magnesium levels in patients who died were higher than in discharged patients (2.10 vs 1.96 mg/dl, p 0.05). CONCLUSIONS: We found no relation between hypomagnesaemia on COVID-19 progression, although hypermagnesaemia could affect COVID-19 mortality (Tab. 4, Ref. 34).

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity.

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

Clinical characteristics of COVID-19-infected cancer patients, Isfahan, Iran.

Background: Cancer patients, as a highly vulnerable population, are receiving a great deal of attention in the current crisis of coronavirus 2019 (COVID-19). To date, shreds of evidence are not sufficient to the description of COVID-19 outcomes in patients with cancer. This study was performed to evaluate the demographic and clinical characteristics and subsequent outcomes of COVID-19 in cancer patients. Materials and Methods: A hospital-based study was conducted involving 66 cancer patients with a confirmed diagnosis of COVID-19 from January 15, 2020, to December 21, 2020, in Isfahan, Iran. The clinical information was collected by interview and medical records. The statistical analyses were performed to describe categorical variables as well as mean, standard deviation, median, and the interquartile range for quantitative variables. Results: In our study, 66 cancer patients with confirmed COVID-19 (age: 17-97 years; 50% female) were included. Leukemia and bone marrow cancer with a frequency of 25.7% were the most common types of cancer among them. Cancer patients mostly complained of fever, cough and fatigue, and shortness of breath. Among 76.9% of patients discharged from the hospital with relative recovery, 23% died; the most common cause of death was acute respiratory distress syndrome. Age, gender, and type of cancer did not affect cancer mortality. COVID-19 had no potential effect to increase the risk of side effects of anticancer therapies. Conclusion: The results of our studies revealed that cancer is an important risk factor for the higher rate of mortality in patients with COVID-19. These findings could help physicians for the management, treatment, and supportive care of COVID-19 cancer patients.

Pharmacological interventions for preventing anthracycline-induced clinical and subclinical cardiotoxicity: A network meta-analysis of metastatic breast cancer.

OBJECTIVE: Doxorubicin- and epirubicin-induced cardiotoxicities are life threatening for those suffering from breast cancer. Comparing the effects of different strategies on the prevention of these agent-induced cardiotoxicities remains unexplored.Data sources: A comprehensive review of clinical trials was performed on the prevention of epirubicin- and/or doxorubicin-induced cardiotoxicity in HER2-positive metastatic breast cancer patients. The reduction in ejection fraction was directed at evaluating cardiac toxicity.Data summary: Fourteen articles evaluated cardiotoxicity as a condition among 2945 individuals, evaluating doxorubicin, epirubicin, Liposomal Doxorubicin (LD), Pegylated Liposomal Doxorubicin (PLD), dexrazoxane plus doxorubicin or epirubicin, and Angiotensin-Converting Enzyme Inhibitors (ACEIs) plus doxorubicin. Pooled Odds Ratio (OR) of 0.043 with a 95% credible interval (CrI) between 0.005 and 0.22 indicated that the dexrazoxane plus epirubicin reduced the number of cardiac events compared with doxorubicin. Furthermore, doxorubicin and epirubicin represented the most effective interventions with a 52% probability of success. Also, the best treatment for reducing Congestive Heart Failure (CHF) was dexrazoxane plus epirubicin with a probability of 43%. For the Left Ventricular Ejection Fraction (LVEF) reduction outcome, ACEIs plus doxorubicin was ranked first with a success probability of 61.2% and they could significantly prevent the reduction in LVEF compared with LD, epirubicin, or doxorubicin. CONCLUSION: Our data suggested that angiotensin-converting enzyme inhibitors and dexrazoxane plus epirubicin were the most effective interventions for preventing cardiotoxicity and CHF. However, ACEIs plus doxorubicin was the best treatment for preventing LVEF reduction.

Magnesium intake and lung cancer risk: A systematic review and meta-analysis.

Magnesium may reduce the risk of lung cancer by affecting cell proliferation, inflammation and by preserving lung function; however, the results of epidemiological studies on the potential benefits of magnesium in lung pathology are inconclusive. We conducted this meta-analysis to investigate the association between magnesium intake and the risk of lung cancer. A total of 5 studies were extracted from PubMed, SCOPUS, and the Cochrane Review (to May 2018). These studies involved 58,5821 participants with 8,977 lung cancer cases. The pooled relative risk (RR) indicated a significant association between lung cancer incidence and magnesium intake (RR = 0.88, 95% CI = 0.79 to 0.98; p = 0.018). To investigate the cause of heterogeneity of these studies (I2 = 75.8%, p < 0.001), we performed a subgroup analysis which was affected by the mean dose of magnesium intake, where doses of magnesium intake lower than 300 mg/d significantly decreased lung cancer risk (RR = 0.83, 95% CI = 0.70 to 0.99; p = 0.034). Increasing magnesium intake doses to over 300 mg/d did not reduce the incidence of lung cancer (RR = 0.89, 95% CI = 0.78 to 1.01; p = 0.076). Our meta-analysis suggests that magnesium intake of less than 300 mg/d may have protective effects in lung cancer.

Co-infection between the severe acute respiratory syndrome coronavirus 2 and the influenza Type B in Isfahan, Iran.

BACKGROUND: Some studies have been reported the rates of co-infection between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus in the different regions. In this study, we report the co-infection rates between SARS-CoV-2 and influenza type B in Isfahan, Iran. MATERIALS AND METHODS: All patients with a definite diagnosis of coronavirus disease 2019 (COVID-19) from Isfahan COVID-19 registry (I-core) study were enrolled from February 2020. RESULTS: Of the 1639 laboratory COVID-19 confirmed in Isfahan province, only two persons were positive for Influenza B from Isfahan COVID-19 registry (I-core). Both patients were symptom-free after 3 months' follow-up. CONCLUSION: During influenza season, differentiating other causes of respiratory illness from COVID-19 is difficult, because common clinical manifestations of COVID-19 mimic those of influenza. It seems that evaluating for co-infection with different types of influenza viruses in patients with specific settings should be considered.

The value of thoracic computed tomography scan comparing to reverse transcription-polymerase chain reaction for the diagnosis of COVID-19.

BACKGROUND: Novel coronavirus disease of 2019 (COVID-19) is the current pandemic causing massive morbidity and mortality worldwide. The gold standard diagnostic method in use is reverse transcription-polymerase chain reaction (RT-PCR) which cannot be solely relied upon. Computed tomography (CT) scan is a method currently used for diagnosis of lung disease and can play a substantial role if proved helpful in COVID-19 diagnosis. We conducted this study to evaluate the diagnostic value of CT scan compared to RT-PCR in the diagnosis of COVID-19. MATERIALS AND METHODS: We recruited 291 hospitalized patients suspicious of COVID-19 according to typical clinical findings during February-March 2020. The patients underwent CT-scan and RT-PCR procedures on the day of hospital admission. CT scans were reported by two radiologists as typical, indeterminate, negative, and atypical. Statistical indices were calculated twice: once considering "typical" and "indeterminate" categories as positive and the other time counting "typical" results as positive. RESULTS: The CT reports were classified as typical (64.95%), indeterminate (10.31%), atypical (11%), and negative (13.75%). Considering "typical" and "intermediate" as positive, sensitivity and specificity were 85.3% and 38.8%, respectively, and using the second assumption, the mentioned indices were 75.9% and 50.4%, respectively. CONCLUSION: According to our study, CT results do not create enough diagnostic benefit and could result in incorrect confidence if negative. Since widely available, CT integration in the clinical process may be helpful in screening of suspected patients in epidemics. Yet, suspected patients should be isolated till confirmed by (multiple) PCRs.

Apolipoprotein B gene mutation related to familial hypercholesterolemia in an Iranian population: With or without hypothyroidism.

BACKGROUND: Familial hypercholesterolemia (FH) leads to elevated low-density lipoprotein cholesterol (LDL-C) levels in plasma. Mutations of its related gene; apolipoprotein B (APOB) is seen in about two percent of the patient with FH. Thyroid disease is usually part of the exclusion criteria for the detection of FH which alters the lipid profile. We evaluated mutations in the APOB gene in patients with high LDL-C levels. MATERIALS AND METHODS: Patients aged between 2 and 80 years with at least one LDL-C level of more than 190 mg/dl were selected (120 patients) from Isfahan Laboratories. Blood samples were obtained from all patients. Genomic DNA was extracted. Primer sequences were designed by Oligo 7.60 to amplify the desired 844 bp region of exon 26 of the APOB gene containing R3500Q and R3500W variants associated with FH. RESULTS: Overall, two patients showed a heterozygous form of a common pathogenic variant in exon 26 named c. 10579 C > T (R3500W, cDNA.10707), and one patient was hypothyroidism. We also recognized another nonpathognomonic variant c. 10913G > A (rs1801701, cDNA.11041) in 13 patients, two of them were hypothyroidism. CONCLUSION: This study for the first time shows the coexistence of APOB mutation in hypothyroidism, which emphasis screening of patients with hypothyroid for FH detection.

Therapeutic inhibition of microRNA-21 (miR-21) using locked-nucleic acid (LNA)-anti-miR and its effects on the biological behaviors of melanoma cancer cells in preclinical studies.

BACKGROUND: Melanoma is a cancer that has a high mortality rate in the absence of targeted therapy. Conventional therapies such as surgery, chemotherapy, and radiotherapy are associated with poor prognosis. The expression of miR-21 appears to be of clinical importance, and the regulation of its expression appears to be an opportunity for treatment. METHODS: In this current study, we aimed to evaluate the effects of miR-21 inhibition in- vitro and in-vivo. In-vitro studies have investigated LNA-anti-miR-21 in mouse melanoma cells (B16F10), and in-vivo studies have proposed a model of melanoma in male C57BL/6 mice. To evaluate the anticancer effects of LNA-anti-miR-21, a QRT-PCR analysis was performed using the 2-ΔΔCT method to determine the degree of inhibition of oncomiR-21. The MTT test, propidium iodide/AnnexinV in-vitro, and tumor volume measurement using the QRT-PCR test with the 2-ΔΔCT method were used to estimate the inhibition of miR-21 and the expression of downstream genes including: SNAI1, Nestin (Nes), Oct-4, and NF-kB following miR-21 inhibition. Finally, immunohistochemistry was conducted for an in-vivo animal study. RESULTS: MiR-21 expression was inhibited by 80% after 24 h of B16F10 cell line transfection with LNA-anti-miR-21. The MTT test showed a significant reduction in the number of transfected cells with LNA-anti-miR-21. The transfected cells showed a significant increase in apoptosis in comparison with the control and scrambled LNA groups. According to our in vivo findings, anti-miR-21 could reduce tumor growth and volume in mice receiving intraperitoneal anti-miR after 9 days. The expression of the SNAI1gene was significantly reduced compared to the controls. Immunohistochemical analysis showed no change in CD133 and NF-kB markers. CONCLUSION: Our findings suggest LNA-anti-miR-21 can be potentially used as an anticancer agent for the treatment of melanoma.

Protective effects of doxepin cream on radiation dermatitis in breast cancer: A single arm double-blind randomized clinical trial.

AIMS: Breast cancer is the most frequently occurring cancer in women. Lumpectomy followed by radiotherapy is suggested to be as effective as a total mastectomy. Radiation-induced dermatitis often occurs as a result of breast radiotherapy. Recent studies suggest that doxepin has promising anti-inflammatory properties. This study was undertaken to evaluate the effects of doxepin therapy on radiation dermatitis. METHODS: A double-blind randomized clinical trial was launched from 2016 to 2017, with a total of 48 patients who had undergone breast-conserving surgery and received postoperative radiation therapy. Radiotherapy was applied 5 days per week for 5 weeks. Adverse dermatological effects were evaluated by a physician at the beginning of the fifth week of radiotherapy and the patients were then randomly assigned (1:1 ratio) to receive either doxepin (5%) or placebo cream for 7 days. RESULTS: There were no significant differences in the dermatitis grade between doxepin and placebo groups at baseline (P > .5). The occurrence of acute dermatitis (grade 2 or higher) was significantly lower with the use of doxepin than with placebo (P ≤ .0001, Zα = 1.96 at 95% confidence interval). CONCLUSION: Doxepin cream prevents dermatitis grade 2 or higher during post-operative breast irradiation. Doxepin cream is easy to use, affordable and prevents pain and irritation.

Preventive Effect of L-Carnitine on Scar Formation During Acute Pyelonephritis: A Randomized Placebo-Controlled Trial.

BACKGROUND: Urinary tract infection and pyelonephritis are clinical problems that frequently occur in children. Several factors are responsible for renal tissue injury, morbidity, and renal scarring after pyelonephritis. The aim of this study was to evaluate the preventive effect of L-carnitine on renal scarring in acute pyelonephritis. METHODS: A randomized double-blind clinical trial was conducted on 65 children aged 6 months to 10 years. Patients were randomized into 2 groups to receive 7-day treatment with only antibiotics without L-carnitine (control group; n = 32) and 7-day treatment with L-carnitine (case group; n = 33) during the acute phase of infection. Technetium-99m-labeled dimercaptosuccinic acid (DMSA) scintigraphy was performed for all children during the acute phase (in 2-7 days of hospitalization) and late phase. P-value less than 0.05 was statistically significant. RESULTS: We recruited 65 participants in the study: 32 children in control group and 33 children in case group. Three children in the control group and 2 children in the case group refused to perform the second DMSA scan. Overall, data analysis at the end of the study was done on 60 patients. Age distribution of girl patients with upper urinary infection was 6.5% in girl children aged between 6 months and 12 months, 41.1% aged between 1 and 5 years, 33.3% aged between 5 and 10 years, respectively. There was no significant difference between 2 groups in age and sex. There was no significant difference between 2 groups in systolic blood pressure, diastolic blood pressure, the lab data including urine white blood cells and serum erythrocyte sedimentation rate, and antibiogram profiles. Voiding dysfunction was detected in 10% of the participants. The baseline DMSA was not significantly difference in 2 groups, but worsening of kidney lesions was significantly higher in control group after 6 months (P = 0.012). CONCLUSION: Our study showed that L-carnitine significantly decreased renal scarring because of acute pyelonephritis.

Visceral Obesity and Its Shared Role in Cancer and Cardiovascular Disease: A Scoping Review of the Pathophysiology and Pharmacological Treatments.

The association between obesity, cancer and cardiovascular disease (CVD) has been demonstrated in animal and epidemiological studies. However, the specific role of visceral obesity on cancer and CVD remains unclear. Visceral adipose tissue (VAT) is a complex and metabolically active tissue, that can produce different adipokines and hormones, responsible for endocrine-metabolic comorbidities. This review explores the potential mechanisms related to VAT that may also be involved in cancer and CVD. In addition, we discuss the shared pharmacological treatments which may reduce the risk of both diseases. This review highlights that chronic inflammation, molecular aspects, metabolic syndrome, secretion of hormones and adiponectin associated to VAT may have synergistic effects and should be further studied in relation to cancer and CVD. Reductions in abdominal and visceral adiposity improve insulin sensitivity, lipid profile and cytokines, which consequently reduce the risk of CVD and some cancers. Several medications have shown to reduce visceral and/or subcutaneous fat. Further research is needed to investigate the pathophysiological mechanisms by which visceral obesity may cause both cancer and CVD. The role of visceral fat in cancer and CVD is an important area to advance. Public health policies to increase public awareness about VAT's role and ways to manage or prevent it are needed.

Isfahan COvid-19 REgistry (I-CORE): Design and methodology.

Health authorities usually exploit after-action reports to collect data on their experience in responding to public health emergencies. To develop an effective approach to manage and learning from health emergencies, we have launched Isfahan COvid-19 REgistry for data collection during routine clinical care as a first "critical incident registry" in Iran. Registries can be employed to explain the natural history of the disease, learn about a particular disease in terms of patient outcomes, the cost-effectiveness of clinical management, monitoring the quality of health-care service, and developing research hypotheses.

PPAR γ agonist, pioglitazone, suppresses melanoma cancer in mice by inhibiting TLR4 signaling.

BACKGROUND: Although previous studies demonstrated an anticancer effect for the ligands of peroxisome proliferator-activated receptor gamma (PPARγ) through activation of its anti-inflammatory responses, nevertheless the anti-tumor mechanism of PPARγ has not been intensively investigated. One of the molecules involved in cancer progression is toll-like receptor 4 (TLR4). METHODS: B16F10 melanoma cells were cultured with or without LPS for 24 hr. The cells were subcutaneously injected to two groups of C57BL/6 mice. After the development of palpable tumors each group of animals were divide to four sub-groups and received pioglitazone in different dose ranges (0,10,50,100 mg/kg/day) for 10 days. At the end of the study, the expression of Tlr4, Myd-88, Nf-kb1 genes was evaluated by qRT-PCR in different groups in mice tumor. The TLR-4 protein expression was evaluated by IHC. TNF-α level in mice tumor and serum were measured by ELISA kits. Tumor volume was measured with Vernier calipers. RESULTS: We observed that activation of PPARγ by its agonist, pioglitazone, reduces tumor volume, Tlr-4, Myd-88, Nf-kb1 mRNA expression, TLR4 protein expression and TNF-α production in melanoma tumor especially in groups that were injected with LPS -stimulated cells. Moreover, treatment of melanoma cells with pioglitazone showed that the inhibitory effects of pioglitazone on LPS-induced inflammatory responses were TLR4 dependent. CONCLUSIONS: The results indicate that pioglitazone, a PPARγ agonist, has a beneficial protective effect against melanoma via interfering with the TLR4-dependent signaling pathways.