Evaluation of T helper17 as skeletal homeostasis factor in peripheral blood mononuclear cells and T helper cells of end-stage renal disease cases with impaired parathyroid hormone.

BACKGROUND: Chronic renal failure is mainly connected with high and low parathyroid hormone (PTH) levels and immunological impairments. The present study aimed to evaluate T helper 17 (Th17) cells as a crucial modulator of the immune system and skeletal homeostasis in hemodialysis patients with impaired intact PTH (iPTH). METHODS: In this research, blood samples were taken from ESRD patients with high (> 300 pg/mL), normal (150-300 pg/mL), and low (< 150 pg/mL) serum intact parathyroid hormone (iPTH( levels (n = 30 in each group). The frequency of Th17 (CD4+ IL17+) cells was evaluated by flow cytometry in each group. The expression levels of Th17 cell-related master transcription factors, cytokines in peripheral blood mononuclear cells (PBMC), and Th cells, and the level of the mentioned cytokines were determined in the supernatant of PBMCs. RESULTS: The number of Th17 cells remarkably increased in subjects with high iPTH against low and normal iPTH. Also, RORÉ£t and STAT3 levels were significantly higher in high iPTH ESRD patients than in other groups in the expression of mRNA and protein levels. These findings are confirmed by evaluating the IL-17 and IL-23 in the supernatant of cultured PBMCs and isolated Th cells. CONCLUSION: Our findings indicated that increased serum PTH levels in hemodialysis cases may be involved in increasing the differentiation of CD4 + cells to Th17 cells in PBMC.

Efficacy of Topical Losartan in Management of Mammoplasty and Abdominoplasty Scars: A Randomized, Double-Blind Clinical Trial.

BACKGROUND: Annually, millions of people suffer from skin scars' psychological and physical disadvantages. Pathologic scars prevention is challenging and requires developing feasible and effective therapeutic strategies. Regarding promising results of losartan (an angiotensin 1 receptor inhibitor) on skin scar in preclinical studies, we aimed to assess the losartan ointment's impact on surgical scars in a clinical setting. MATERIAL AND METHOD: Twenty-four patients with surgical wounds were enrolled from Razi hospital's plastic and reconstructive surgery department. The patients were trained to apply ointments 14-18 days post-surgery on the determined scar side, twice a day for 6 months. Two dermatologists independently evaluated scar formation at 3 and 6-month follow-ups using the Vancouver Scar Scale (VSS) score. RESULT: Twenty-four female patients with cosmetic surgeries were included. The mean VSS score of losartan-treated sides was 7.1 ± 2.06 (at month 3) and 5.21 ± 1.71 (at month 6) that significantly were different from placebo-treated sides (9.77 ± 1.55 and 8.31 ± 1.88 at 3 and 6 months, respectively) (P value < 0.001 and < 0.001, respectively, for months 3 and 6). The subset analysis demonstrated a significant improvement in height (P value < 0.001 at 3 and 6 months), pliability (P value < 0.001 at 3 and 6 months), and vascularity (P value < 0.001 at 3 and 6 months) subsets at losartan compared to placebo-treated side. Losartan ointment was well tolerated with no complication. CONCLUSION: Losartan ointment successfully improved scar formation in mammoplasty and abdominoplasty patients. The losartan preventive effect should be confirmed in future large-scale studies with long-term follow-ups. LEVEL OF EVIDENCE II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors   www.springer.com/00266 .

Application of Emerging Plant-Derived Nanoparticles as a Novel Approach for Nano-Drug Delivery Systems.

Nanotechnology has enabled the delivery of small molecular drugs packaged in nanosized vesicles to the target tissues. Plant-Derived Nanoparticles (PDNPs) are vesicles with natural origin and unique properties. These nanoparticles have several advantages over synthetic exosomes and liposomes. They provide bioavailability and biodistribution of therapeutic agents when delivered into different tissues. These nanoparticles can be modified according to the specificity of their functions in target tissues. When PDNPs are internalized, they can induce stem cells proliferation, reduce colitis injury, activate intrinsic and extrinsic apoptosis pathways, and inhibit tumor growth and progression. These properties make them potential drug delivery systems in targeting diseased tissues, such as inflammatory regions and different cancers.

T lymphocytes and preeclampsia: The potential role of T-cell subsets and related MicroRNAs in the pathogenesis of preeclampsia.

Innate and adaptive immune systems have a crucial role in initiating and progressing some pregnancy disorders such as preeclampsia (PE), which is one of the pregnancy-specific disorders that could result in neonatal and maternal morbidity and mortality. The dysregulation of the spiral artery and inadequate trophoblast invasion lead to PE symptoms through producing various inflammatory cytokines and anti-angiogenic factors from the placenta. T lymphocytes play a special role in the epithelium and stroma of the human endometrium. CD4+ T helper (Th) cells, Th1/Th2, and Th17/T regulatory (Treg) balance mainly contribute to the establishment of a pregnancy-favorable environment. This review examined the dysregulation of some cytokines produced from T cells, the dysregulation of the transcription factors of Th cells, the expression of chemokine receptors on T cells, as well as the effects of some factors including vitamin D on the activity of T cells, and finally, the dysregulation of various miRNAs related to T cells, which could cause PE.

Any closer to successful therapy of multiple myeloma? CAR-T cell is a good reason for optimism.

Despite many recent advances on cancer novel therapies, researchers have yet a long way to cure cancer. They have to deal with tough challenges before they can reach success. Nonetheless, it seems that recently developed immunotherapy-based therapy approaches such as adoptive cell transfer (ACT) have emerged as a promising therapeutic strategy against various kinds of tumors even the cancers in the blood (liquid cancers). The hematological (liquid) cancers are hard to be targeted by usual cancer therapies, for they do not form localized solid tumors. Until recently, two types of ACTs have been developed and introduced; tumor-infiltrating lymphocytes (TILs) and chimeric antigen receptor (CAR)-T cells which the latter is the subject of our discussion. It is interesting about engineered CAR-T cells that they are genetically endowed with unique cancer-specific characteristics, so they can use the potency of the host immune system to fight against either solid or liquid cancers. Multiple myeloma (MM) or simply referred to as myeloma is a type of hematological malignancy that affects the plasma cells. The cancerous plasma cells produce immunoglobulins (antibodies) uncontrollably which consequently damage the tissues and organs and break the immune system function. Although the last few years have seen significant progressions in the treatment of MM, still a complete remission remains unconvincing. MM is a medically challenging and stubborn disease with a disappointingly low rate of survival rate. When comparing the three most occurring blood cancers (i.e., lymphoma, leukemia, and myeloma), myeloma has the lowest 5-year survival rate (around 40%). A low survival rate indicates a high mortality rate with difficulty in treatment. Therefore, novel CAR-T cell-based therapies or combination therapies along with CAT-T cells may bring new hope for multiple myeloma patients. CAR-T cell therapy has a high potential to improve the remission success rate in patients with MM. To date, many preclinical and clinical trial studies have been conducted to investigate the ability and capacity of CAR T cells in targeting the antigens on myeloma cells. Despite the problems and obstacles, CAR-T cell experiments in MM patients revealed a robust therapeutic potential. However, several factors might be considered during CAR-T cell therapy for better response and reduced side effects. Also, incorporating the CAT-T cell method into a combinational treatment schedule may be a promising approach. In this paper, with a greater emphasis on CAR-T cell application in the treatment of MM, we will discuss and introduce CAR-T cell's history and functions, their limitations, and the solutions to defeat the limitations and different types of modifications on CAR-T cells.

Merkel Cell Polyomavirus Gene Expression and Mutational Analysis of Large Tumor Antigen in Non-Merkel Cell Carcinoma Tumors of Iranian Patients.

INTRODUCTION: The presence of Merkel cell polyomavirus (MCPyV) was identified in Merkel cell carcinoma (MCC). However, there was sparse information on the link of other common nonmelanoma skin cancers - basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) - to MCPyV infection. The current study describes the phylogenetic information of MCPyV isolated from Iranian non-MCC (nonmelanoma skin cancers) focusing on tumorigenesis of mutations in large tumor (LT) antigen (LT-Ag) fragment. METHODS: Sixty patients with BCC and 20 patients with SCC were included in this study (48 males and 32 females; average age 65 years). The MCPyV-DNA copy number in positive samples was measured by quantitative real-time PCR. Then, mutational analysis of the MCPyV LT gene was carried out by direct sequencing. RESULTS: While MCPyV DNA was detected in 6 (10%) of 60 BCC samples, no viral genome was found in SCCs. There was no distinct association of MCPyV positivity with gender, age, or type of tumor (BCC or SCC) (p value >0.05). Quantitative real-time PCR revealed that the median number of viral DNA copies per cell was 0.7 in 6 MCPyV-positive BCC samples. Furthermore, full-length LT-Ag sequencing of positive samples indicated no stop codon or frameshift mutations compared to reference sequences. CONCLUSION: Considering the important role of the LT-Ag in the pathogenicity of MCPyV, non-synonymous mutations compared with the reference proteins triggered relevant amino acid substitutions. Overall, the results showed no tumor-associated mutations in the LT-Ag sequence of MCPyVs from positive samples.

Effect of Dextrose Prolotherapy, Platelet Rich Plasma and Autologous Conditioned Serum on Knee Osteoarthritis: A Randomized Clinical Trial.

Knee osteoarthritis (OA) is one of the common degenerative articular disorders that are related to decreased quality of life. Currently, novel biologic therapeutic approaches are introduced in the literature for OA management. In this study, the clinical efficiency of Dextrose prolotherapy, platelet-rich plasma (PRP) and autologous conditioned serum (ACS) injection on the level of pain and function in Knee OA were compared. A randomized clinical trial was directed on 92 knee OA patients. Patients were randomly divided into three groups: 30 were received dextrose prolotherapy once in a week for three weeks, 30 received autologous PRP for two times with seven days interval, and in the remaining 32 patients 2ml of ACS were injected two times every seven days. Study participants were measured through the Western Ontario and McMaster Universities (WOMAC) score, the visual analogue scale (VAS), at baseline, 1 and 6 months post-intervention. Both ACS and PRP treated patients showed improvement in pain intensity and knee function during 1 and 6 months pursue; however, this progress was more significant in the ACS group. Dextrose prolotherapy showed no substantial changes in pain and function of the affected knee in treated patients. Treatment of Knee OA with ACS and PRP injections are associated with pain reduction and knee function improvement. Not only, ACS therapy is more effective than that of PRP, but also due to its less variability in processing and less reported side effects, it could be considered as a safe and effective non-surgical alternative for OA management.

A Dual-Type L2 11-88 Peptide from HPV Types 16/18 Formulated in Montanide ISA 720 Induced Strong and Balanced Th1/Th2 Immune Responses, Associated with High Titers of Broad Spectrum Cross-Reactive Antibodies in Vaccinated Mice.

E. coli-derived concatenated, multitype L2-conserved epitopes of human papillomavirus (HPV) L2 protein might represent a less expensive and pan-type vaccine alternative (compared to type-specific HPV L1 virus-like particles), if stable protein expression and strong immunogenicity features could be met. Herein, three dual-type- (DT-) HPV L2 fusion peptides comprising the three head-to-tail tandem repeats (multimers) of either HPV 16 epitope "17-36" or "69-81" or one copy (monomer) of 11-88 fused to the same residues of HPV 18 were constructed and expressed in E. coli. SDS-PAGE and Western blot analyses indicated the proper expression and stability of the E. coli-derived DT peptides. Mice immunized by formulation of the purified DT peptides and Freund's adjuvant (CFA/IFA) raised neutralizing antibodies (NAbs; the highest for DT: 11-88 peptide) which showed proper cross-reactivity to HPV types: 18, 16, 31, and 45 and efficiently neutralized HPV 18/16 pseudoviruses in vitro. Immunization studies in mice by formulation of the DT: 11-88 × 1 peptide with various adjuvants (alum, MF59, and Montanides ISA 720 and 50) indicated that Montanide adjuvants elicited the highest cross-reactive titers of NAbs and similar levels of IgG1 and IgG2a (switching towards balanced Th1/Th2 responses). The results implied development of low-cost E. coli-derived DT: 11-88 peptide formulated in human compatible ISA 720 adjuvant as a HPV vaccine.