The effect of l‐carnitine supplementation on serum levels of omentin‐1, visfatin and SFRP5 and glycemic indices in patients with pemphigus vulgaris: A randomized,double‐blind,placebo‐controlled clinical trial

Pemphigus vulgaris (PV) is a chronic autoimmune disorder with potentially fatal outcomes. The aim of this study was to investigate the effect of l ‐carnitine (LC) on secreted frizzled‐related protein‐5 (SFRP5), omentin, visfatin, and glycemic indices in PV patients under corticosteroid treatment. In this randomized, double‐blind, placebo‐controlled clinical trial, 52 patients with PV were divided randomly into two groups to receive 2 g of LC or a placebo for 8 weeks. Serum levels of SFRP5, omentin, visfatin, and also glycemic indices were evaluated at the baseline and end of the study. LC supplementation significantly decreased the serum level of visfatin (95% CI [?14.718, ?0.877], p = .05) and increased the serum levels of SFRP5 (95%CI [1.637, 11.380], p < .006) and omentin (95% CI [9.014, 65.286], p < .01). However, LC supplementation had no significant effects on the serum levels of glycemic factors such as insulin (95% CI [?1.125, 3.056], p = .426), fasting blood sugar (95% CI [?4.743, 3.642], p = .894), homeostatic model assessment of insulin resistance (95% CI [?0.305, 0.528], p = .729), and quantitative insulin‐sensitivity check index (95% CI [?0.016, ?0.010], p = .81). LC supplementation decreased visfatin serum level and increased omentin‐1 and SFRP5 serum levels in patients with PV. However, it has no significant effect on the serum levels of insulin and glycemic indices.     

Investigation of the biological activity,mechanical properties and wound healing application of a novel scaffold based on lignin–agarose hydrogel and silk fibroin embedded zinc chromite nanoparticles

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles. Considering the cell viability technique, red blood cell hemolysis in addition to anti-biofilm assays, it was determined that after three days, the toxicity of the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite was less than 13%. Moreover, the small hemolytic effect (1.67%) and high level of prevention in forming a P. aeruginosa biofilm with low OD value (0.18) showed signs of considerable hemocompatibility and antibacterial activity. Besides, according to an in vivo assay study, the wounds of mice treated with the cross-linked lignin–agarose/SF/ZnCr₂O₄ nanobiocomposite scaffold were almost completely healed in five days. Aside from these biological tests, the structural features were evaluated by FT-IR, EDX, FE-SEM, and TG analyses, as well as swelling ratio, rheological, and compressive mechanical study tests. Additionally, it was concluded that adding silk fibroin and ZnCr₂O₄ nanoparticles could enhance the mechanical tensile properties of cross-linked lignin–agarose hydrogel, and also an elastic network was characterized for this designed nanobiocomposite.

Given the important aspects of wound healing approaches, in this work, an innovative biocompatible nanobiocomposite scaffold was designed and prepared based on cross-linked lignin–agarose hydrogel, extracted silk fibroin solution, and zinc chromite (ZnCr₂O₄) nanoparticles.     

Haplotype-Based Association and In Silico Studies of OPRM1 Gene Variants with Susceptibility to Opioid Dependence Among Addicted Iranians Undergoing Methadone Treatment

The associations of OPRM1 gene variants with opioid dependence have been demonstrated. This study investigated the association of rs495491, rs1799971 (A118G), rs589046, and rs10457090 variants of OPRM1 gene with opium dependence and their haplotypes among addicted individuals undergoing methadone treatment. Moreover, we investigated whether any of these variants were associated with libido dysfunction or insomnia among addicted people. A total of 404 individuals were genotyped by amplification refractory mutation system (ARMS) PCR. In silico studies were designed through homology modeling of A118G structures (N40 and D40) and docked with 41 FDA-approved drugs of OPRM1 protein by SWISS-MODEL, COACH, MolProbity, ProSA, Errat, Glide XP, and Autodock 4. Results revealed that rs495491, A118G, rs589046, and rs10457090 were significantly associated with opium dependence under recessive (P = 6.66E-10), dominant (P = 0.017), co-dominant (P = 0.001), and recessive (P = 9.28E-6) models of inheritance, respectively. Further analyses indicated three significant haplotypes including A-A-A-C (P-permutation < 1E-9), G-G-A-C (P-permutation = 0.04), and G-A-G-C (P-permutation = 8.69E-4). Genotype-phenotype associations of OPRM1 variants with insomnia and libido dysfunction showed no significant association. Docking showed the higher binding affinity of N40 rather than D40 model; however, methadone and morphine were bonded with D40 structure more powerful. Consequently, rs495491, A118G, rs589046, and rs10457090 were associated with opioid dependence among Iranians; also, A118G might be the most remarkable marker of OPRM1 owing to its vital structural roles.     

Head and neck non-Hodgkin's lymphoma: a 20-year demographic study of 381 cases

Malignant lymphoma is a lymphoreticular malignancy with considerable geographic variation. The objective of the present study was to provide a preliminary report on patients with head and neck non-Hodgkin's lymphoma (NHL) in a selected Iranian population. In a retrospective review from 1981 through 2001, all cases of NHL occurring in the head and neck region were selected. Histological slides were reviewed and classified according to the Working Formulation. Clinical data including patients’ age, sex, initial anatomic site of disease and presenting symptoms were also recorded. Information on 381 cases of NHL was retrieved from the archived medical records; 281 cases were nodal and 100 extranodal. The mean age of the patients with nodal and extranodal disease was 39.3 and 47.7 years, respectively. A significant difference in gender was noted in the nodal group (P < 0.001), but not in the extranodal cases. The most common site of involvement in the extranodal subjects was Waldayer's ring. According to histopathologic evaluation, 72% of the specimens were intermediate-, 14% were high-, and 12% were low-grade malignancies. Considering the relative frequency of head and neck lymphoma, establishment of a uniform reporting method seems necessary in order to compare different reports from various populations.     

Ultrastructural changes in rat ovarian cells of fetuses and neonates from diabetic mothers

Maternal diabetes leads to increased blood glucose concentration in the mother and consequently in the fetus, causing various neonatal problems. This study was conducted to evaluate the effect of maternal diabetes on fetal ovarian structure. Forty adult female rats were divided into two equal groups. Diabetes was induced in one group by alloxan. Both groups became pregnant by natural mating. At days 14 to 20 of pregnancy and day 30, day 60, and day 90 after birth, the fetuses and neonates were collected from both groups and the female genital system was isolated from them. The numbers of germ cells were measured using routine histological techniques in fetuses. In the neonatal ovarian samples, various cellular parameters were determined using transmission electron microscopy (TEM) technique. Results revealed a significant decrease in the number of germ cells in the fetal female gonads in the gonads of fetuses from diabetic mothers compared to those of control. Results of TEM revealed some differences in the luteal cells and oocytes of primordial follicles in ovaries of neonates from diabetic mothers compared to that of control. Mitochondrial abnormalities were seen as mitochondrial cristae were destroyed and vacuolation occurred in the mitochondria and the nuclei of luteal cells were darken and condensed. It is generally concluded that maternal hyperglycemia affects fetal female gonads illustrated by a decrease in the oocytes and alteration in the mitochondria and nuclei of oocytes and luteal cells in neonatal ovaries.     

Adenovirus-mediated p53 gene therapy in pediatric soft-tissue sarcoma cell lines: sensitization to cisplatin and doxorubicin

Sarcomas, or tumors of connective tissue, represent roughly 20% of childhood cancers. Although the cure rate for sarcomas in general has significantly improved in the last 10 years, there continue to be subgroups that are difficult to treat. High-grade or metastatic soft-tissue sarcomas and rhabdomyosarcomas (RMS) of the extremities remain therapeutic challenges and their prognosis is often poor. The future of sarcoma therapy will likely include molecular approaches including gene/protein expression profiling and gene-based therapy. Most sarcomas harbor defects in the p53 or pRb pathways. The tumor suppressor p53 is central to regulation of cell growth and tumor suppression and restoring wild-type p53 function in pediatric sarcomas may be of therapeutic benefit. Studies with adenoviral-mediated p53 gene transfer have been conducted in many cancer types including cervical, ovarian, prostatic and head and neck tumors. Studies of this approach, however, remain limited in pediatric cancers, including sarcomas. Using three viral constructs containing cDNA for wild-type p53, mutant p53 (C135S) and lacZ, we studied the effect of adenoviral-mediated gene therapy in four pediatric sarcoma cell lines, RD and Rh4 (RMS), Rh1 (Ewing's sarcoma) and A204 (undifferentiated sarcoma). Using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay, we have shown a dose-dependent decrease in cell viability 72 h post-treatment that occurs with Ad-wtp53 but not with Ad-mutp53. Cells treated with Ad-wtp53 show upregulation of the p53 downstream targets, p21(CIP1/WAF1) and bax. Growth curves demonstrate suppression of cell growth over a period of 4 days and cells treated with Ad-wtp53 demonstrate a significant increase in sensitivity to the chemotherapeutic agents, cisplatin and doxorubicin. Our results indicate that restoration of wild-type p53 function in pediatric sarcoma cells could provide a basis for novel approaches to treatment of this disease.