Evaluation of the safety and efficacy of biosimilar recombinant growth hormone in children with growth hormone deficiency: non-inferiority, randomized, parallel, multicentric and Phase III trial.

OBJECTIVES: This study is designed in order to compare the efficacy and safety of recombinant human growth hormone (rhGH) with the reference brand. METHODS: According to the inclusion criteria, 85 people in 13 Iranian centers were randomly selected to receive biosimilar Somatropin (Somatin®) (44 people) and reference Somatropin (Norditropin®) (41 people) at a dose of 35 µg/kg/d, seven days/week for 12 months. The primary outcomes included height velocity (HV) was measured during 12 months of treatment. RESULTS: The two intervention groups' Height changes were similar. The mean HV was 10.96 cm/year in the biosimilar group and 10.05 cm/year in the reference groups after 12 months. Estimates of the lower bounds of 95% CI for mean height differences in the biosimilar intervention group compared to the reference intervention group did not exceed the 2 cm margin. Therefore, the non-inferiority of biosimilar intervention compared to the brand product is verified. Common ADRs in both groups were nausea in two patients (2.4%), diarrhea in two patients (2.4%), increased body temperature in one patient (1.2%), and headache in one patient (1.2%). CONCLUSIONS: The finding of this study indicated that Somatin® and Norditropin® have comparable efficacy and safety profiles. CLINICAL TRIAL REGISTRATION: www.IRCT.irIRCT20171122037571N1.

Effects of coenzyme Q10 supplementation on lipid profiles and liver enzymes of nonalcoholic fatty liver disease (NAFLD) patients: A systematic review and meta-analysis of randomized controlled trials.

As an antioxidant, coenzyme Q 10 (CoQ10) has been proposed as a possible treatment for non-alcoholic fatty liver disease (NAFLD). In the present meta-analysis, we aimed to determine the effects of CoQ10 supplementation on lipid profiles and liver enzymes of NAFLD patients. We searched PubMed, Web of Science, Scopus, and Cochrane Library on 21 April 2022 to retrieve randomized controlled trials on NAFLD patients in which CoQ10 was utilized as a treatment. Data were pooled using the random-effects model and weighted mean difference (WMD) was considered as the summary effect size. The analysis of the six included studies indicated an overall non-significant decrease in the lipid profiles (total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TG)), and liver enzymes (aspartate transaminase (AST), alanine transaminase (ALT), and gamma-glutamyltransferase (GGT)) of NAFLD patients who received CoQ10. Sensitivity analysis using "leave-one out" method showed a significant reduction in AST, and GGT after excluding certain studies. Also, subgroup analyses showed significant difference based on CoQ10 dose for TC, AST, and GGT, and also a significant decrease in AST based on the duration of the intervention. No publication bias was found between the studies. Although an overall non-significant decrease was observed in lipid profiles and liver enzymes of NAFLD patients, the results of sensitivity and subgroup analyses showed significant effects of CoQ10 in certain conditions. Further RCTs should be done in light of our findings.

Risk factors associated with vitamin D deficiency in preterm neonates: a single-center step-wise regression analysis.

BACKGROUND: Vitamin D deficiency is particularly concerning in pregnant women, leading to various health-related issues in mothers and their babies, especially those born prematurely, including neonatal skeletal and respiratory disorders. In addition, there have been several reports indicating the presence of multiple impactful factors in the development of vitamin D deficiency. Therefore, we aimed to evaluate the vitamin D level in very preterm and moderately preterm newborns and investigate its association with presumed influential factors. METHODS: This cross-sectional descriptive study was performed on 54 mothers and their preterm neonates with gestational ages less than 34 weeks at delivery (i.e., very preterm and moderately preterm). After the serum vitamin D levels were determined from samples obtained in the first 24 h after birth, the babies were divided into two groups based on the presence or absence of deficiency. The relationship between several factors and the neonatal serum vitamin D level was investigated separately and in a linear step-wise regression model. RESULTS: The differences between the groups regarding maternal age, gestational age, neonate's gender, birth weight, and delivery method with neonatal vitamin D levels were not statistically significant. However, maternal vitamin D levels strongly correlated with neonatal vitamin D levels (P-value < 0.001, r = 0.636). The regression model also yielded a strong predictive capability (P-value < 0.001, Adjusted R2 = 0.606), with the maternal vitamin D level demonstrating a significant impact. CONCLUSIONS: Low vitamin D levels in pregnant mothers correlate with deficient levels in their preterm neonates. Therefore, as vitamin D deficiency significantly affects both the mother's and newborn's health, it is recommended that healthcare providers provide comprehensive plans for vitamin D supplementation during pregnancy.

The effects of chicory supplementation on liver enzymes and lipid profiles in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of clinical evidence.

BACKGROUND & AIMS: The beneficial effects of Cichorium intybus L., chicory, in patients with non-alcoholic fatty liver disease (NAFLD) are controversial. This review aimed to systematically summarize the evidence on the effects of chicory on liver function and lipid profile in patients with NAFLD. METHODS: Online databases of Scopus, Web of Science, PubMed, EMBASE, Cochrane Library, and grey literature were searched for relevant randomized clinical trials. Weighted mean differences (WMD) with 95% confidence intervals (CIs) were used as effect sizes and a random-effects model was used to pool the data. Besides, sensitivity analyses and publication bias analysis were performed. RESULTS: In total, five articles containing 197 patients with NAFLD were included. The study showed that chicory significantly decreased the levels of both aspartate transaminase (WMD: -7.07 U/L, 95%CI: -13.82 to -0.32) and alanine transaminase (WMD: -17.53 U/L, 95%CI: -32.64 to -2.42). However, no significant effects on alkaline phosphatase and gamma-glutamyl transferase levels and the components of the lipid profile were observed with the use of chicory. CONCLUSIONS: This meta-analysis showed that chicory supplementation may exert potential hepatoprotective effects in patients with NAFLD. However, for widespread recommendations, more studies with a higher number of patients and longer periods of intervention are mandatory.

Streptococcus-related acute suppurative thyroiditis in a COVID-19-positive child: A rare case report.

In this case report, we present a 10-year-old girl with acute suppurative thyroiditis (AST) symptoms, such as fever, sore throat, and swelling in the suprasternal region, who had a positive PCR test for COVID-19. The result of the secretions culture obtained from the abscess drainage was positive for nonhemolytic Streptococcus.

The first presentation of Wolcott-Rallison syndrome in a four-month-old infant with diabetic ketoacidosis (DKA) precipitating by COVID-19: A case report.

Monogenic diabetes mellitus (eg, Wolcott-Rallison syndrome) is a rare condition. It associates with neonatal or early-infancy insulin-dependent diabetes. We reported DKA in the four-month infant as the first presentation of monogenic diabetes that has accelerated by COVID-19 infection. Therefore, considering the concurrency of COVID-19 and DKA is crucial.

Down-regulation of microRNA-19b in hormone receptor-positive/HER2-negative breast cancer.

miR-19b (miR-19b-3p) has been reported to be correlated with either favorable or unfavorable events in several cancers. However, no study has been conducted to evaluate the expression level of miR-19b in patients with breast cancer (BC). This study was aimed to investigate the expression level of miR-19b in human malignant and healthy breast tissues with histopathology of ER+/PR+/HER2-. We performed a miRNA real-time PCR to detect differential expression of miR-19b in 40 BC, including 17 BC with familial background and 23 BC without familial background, and 12 non-tumoral tissues. Moreover, a bioinformatics prediction upon miR-19b functionality in BC cells was performed. The miR-19b expression level was significantly down-regulated in BC, BC with familial background, and BC without familial background compared with its expression in normal tissue (p value, <0.0001; fold change, -7.45; p value, 0.0003; fold change, -6.45; and p value, 0.0005; fold change, -8.41, respectively). Moreover, according to the AUCs (area under curve) of receiver operating characteristic (ROC) curves, miR-19b can significantly distinguish all defined categories. Last, in agreement with our experimental findings, proteoglycans in cancer, pathways in cancer, FoxO signaling pathway, central carbon metabolism in cancer, p53 signaling pathway, transcriptional misregulation in cancer, and prolactin signaling pathway were predicted as miR-19b-related signaling pathways. In summary, down-regulation of miR-19b in BC vs healthy tissue suggests that mir-19b can function as a tumor suppressor. Our results shed additional information on controversial expression pattern of miR-19b depending on different cancer types.

Phylogenetic typing and detection of extended-spectrum ß-lactamases in Escherichia coli isolates from broiler chickens in Ahvaz, Iran.

This study was conducted to reveal the phylogenetic background, to detect the genes encoding TEM, SHV and CTX-M-15 extended-spectrum ß-lactamases (ESBL), and to analyze their distribution in phylo-groups of 150 Escherichia coli isolates from broiler chickens in Ahvaz (Southwest of Iran). Seventy- five cloacal swabs from healthy birds (fecal isolates), and 75 heart blood samples from birds with colibacillosis (septicemic isolates) were obtained. All isolates were phylotyped and screened for ESBL genes by polymerase chain reaction (PCR). The fecal isolates belonged to four main phylo-groups, including 41 isolates (54.67%) to A, 9 (12.00%) to B1, 5 (6.67%) to B2, and 20 (26.67%) to D. Of septicemic isolates, 37 isolates (49.33%) were classified as phylotype A, 5 (6.67%) as B1, 10 (13.33%) as B2, and 23 (30.67%) as D. In molecular analysis, a total of 72 isolates (35 fecal and 37 septicemic) were identified to harbor ESBL genes, which were distributed in phylo-groups A, B1, B2, and D. Regardless of the type of isolate, blaCTX-M-15 gene was the most common genotype, followed by blaTEM and blaSHV genes. This study suggests that broiler chickens in Iran are infected to ESBL genes- harboring Escherichia coli strains which may be spread to the food chain through fecal contamination of carcasses during slaughtering.

Effects of Crocin Supplementation during In Vitro Maturation of Mouse Oocytes on Glutathione Synthesis and Cytoplasmic Maturation.

BACKGROUND: Crocin is an active ingredient of saffron (Crocus sativus L.) and its antioxidant properties have been previously investigated. This carotenoid scavenges free radicals and stimulates glutathione (GSH) synthesis; consequently, it may protect cells against oxidative stress. The aim of this research is to protect oocytes from oxidative stress by the addition of a natural source antioxidant. MATERIALS AND METHODS: In the present in vitro experimental study, we collected cumulus oocyte complexes (COCs) from mouse ovaries of euthanized, 6-8 week-old female Naval Medical Research Institute (NMRI) mice. Oocytes were subjected to in vitro maturation (IVM) in the presence of either crocin (5 or 10 µg/ml), 5 mM buthionine-[S-R]- sulfoximine (BSO), or the combination of crocin plus BSO. Oocytes that matured in vitro in a medium without crocin or BSO supplements were considered as controls. Following 16-18 hours of IVM, matured oocytes (n=631) were fertilized by capacitated sperm from NMRI male mice, and cultured in vitro for up to 96 hours to assess preimplantation embryonic development. The levels of GSH in metaphase II (MII) oocytes after IVM (n=240) were also assessed by the 5, 5-dithio-bis (2-nitrobenzoic acid) (DTNB)-GSH reductase recycling assay. RESULTS: Supplementation of IVM media with 10 µg/ml crocin significantly (P<0.05) increased nuclear maturation, preimplantation development and GSH concentrations compared with the control group. Maturation of oocytes in IVM medium supplemented with BSO alone or the combination of 5 µg/ml crocin and BSO drastically decreased GSH concentrations and subsequently resulted in low rates of maturation, fertilization and blastocyst development. However, the combination of 10 µg/ml crocin with 5 mM BSO increased the level of nuclear maturation which was comparable to the control group. CONCLUSION: Supplementation of IVM media with crocin can improve nuclear maturation rates and subsequent developmental potential of mouse oocytes. This may occur by its beneficial effect in increasing GSH concentrations in MII oocytes.

A comparative study of saffron aqueous extract and its active ingredient, crocin on the in vitro maturation, in vitro fertilization, and in vitro culture of mouse oocytes.

OBJECTIVE: Reactive oxygen species have effects on gamete quality and gamete interaction; they influence spermatozoa, oocytes, embryos, and their environment. In this study, we evaluated the antioxidant effect of different concentrations of saffron (Crocus sativus L.) aqueous extract (SAE) and its ingredient, crocin, on the improvement of in vitro maturation (IVM) and subsequent in vitro fertilization (IVF) and embryo development of mouse oocytes. MATERIALS AND METHODS: Cumulus oocyte complexes were collected from ovaries, and germinal vesicle oocytes were cultured in the presence of SAE and crocin. SAE was added at dosages of 5 µg/mL, 10 µg/mL, and 40 µg/mL; dosages of crocin were 50 µg/mL, 100 µg/mL, and 400 µg/mL. All dosages were added to maturation medium and a group without SAE or crocin was considered as the control group. Following IVM, metaphase II oocytes were fertilized and cultured in vitro in order to observe embryo development. RESULTS: Both SAE and crocin improved the rate of IVM, IVF, and in vitro culture. Addition of 40 µg/mL SAE to maturation medium significantly increased the rate of IVM, IVF, and in vitro culture (p < 0.05). Furthermore 100 µg/mL crocin significantly increased the IVM rate compared to the control group (p < 0.05). CONCLUSION: Use of SAE during IVM can affect on IVM, IVF, and early embryo development in a dose-dependent manner. SAE appears to have a stronger effect than pure crocin.

Evaluation effects of allopurinol and FSH on reduction of ischemia-reperfusion injury and on preservation of follicle after heterotopic auto-transplantation of ovarian tissue in mouse.

Purpose: Allopurinol and FSH injection are applied to reduce ischemia-reperfusion injury and to increase survival rate for ovarian follicles after ovarian heterotopic autotransplantation in mice. Methods: Ovarian tissues from 6-week-old mice were grafted into back muscle then collected after 3 weeks. A total of five groups were included in this experiment as follows: control group (n = 5), sham-operated group (n = 5), allopurinol treatment group (AP) (n = 5), follicle stimulating hormone (FSH) treatment group (n = 5), as well as, allopurinol and FSH treatment group (APF) (n = 5). We investigated survival, number and development of follicles, vaginal cytology along with plasma malondialdehyde (MDA) concentration in grafted ovary. Results: Total follicles count significantly increased in APF group compared with other treatment groups (p < 0.05). MDA concentration significantly decreased in AP group and APF treatment group compared with sham-operated group. In AP group, vaginal smears showed presence of cornified epithelial cells three-five day after surgery. Conclusions: We demonstrated that allopurinol, as a XO inhibitor, plays an important role in order to decrease ischemia injury and to increase survival rate for follicles. Also, FSH, as a folliculogenesis and angiogenesis factor, increases development of follicles. It seems that allopurinol can cause re-establishing hypothalamus-pituitary axis and finally can restore estrous cycle earlier than for the sham operated group, so it explains the increasing survival rate for follicles.