The effect of Wharton's jelly-derived stem cells seeded/boron-loaded acellular scaffolds on the healing of full-thickness burn wounds in the rat model.

Burn wounds are the most destructive and complicated type of skin or underlying soft tissue injury that are exacerbated by a prolonged inflammatory response. Several cell-based therapeutic systems through the culturing of potent stem cells on modified scaffolds have been developed to direct the burn healing challenges. In this context, a new regenerative platform based on boron (B) enriched-acellular sheep small intestine submucosa (AOSIS) scaffold was designed and used as a carrier for mesenchymal stem cells derived from Wharton's jelly (WJMSCs) aiming to promote the tissue healing in burn-induced rat models. hWJMSCs have been extracted from human extra-embryonic umbilical cord tissue. Thereafter, 96 third-degree burned Wistar male rats were divided into 4 groups. The animals that did not receive any treatment were considered as group A (control). Then, group B was treated just by AOSIS scaffold, group C was received cell-seeded AOSIS scaffold (hWJMSCs-AOSIS), and group D was covered by boron enriched-cell-AOSIS scaffold (B/hWJMSCs-AOSIS). Inflammatory factors, histopathological parameters, and the expression levels of epitheliogenic and angiogenic proteins were assessed on 5, 14 and 21 d post-wounding. Application of the B/hWJMSCs-AOSIS on full-thickness skin-burned wounds significantly reduced the volume of neutrophils and lymphocytes at day 21 post-burning, whilst the number of fibroblasts and blood vessels enhanced at this time. In addition, molecular and histological analysis of wounds over time further verified that the addition of boron promoted wound healing, with decreased inflammatory factors, stimulated vascularization, accelerated re-epithelialization, and enhanced expression levels of epitheliogenic genes. In addition, the boron incorporation amplified wound closure via increasing collagen deposition and fibroblast volume and activity. Therefore, this newly fabricated hWJMSCs/B-loaded scaffold can be used as a promising system to accelerate burn wound reconstruction through inflammatory regulation and angiogenesis stimulation.

The association of Treg and Th17 cells development factors and anti-TPO autoantibodies in patients with recurrent pregnancy loss.

OBJECTIVES: Thyroid autoimmunity is considered as the most prevalent autoimmune condition in women in fertility age. There are different clinical evidences indicating the association between thyroid autoimmunity and increased risk of RPL. This study aimed to analyze the association of Tregs and Th17 cells development factors and anti-thyroid peroxidase (anti-TPO) antibodies in RPL patients. Healthy controls (n = 36), TPO + controls (n = 25) and TPO + RPL (n = 32) participated in this study. After blood sampling, the frequency of Th17 and Tregs was evaluated using flow cytometry. Real-time PCR and ELISA was used to assess the status of Tregs and Th17 related transcription factors and cytokines in mRNA and protein level, respectively. RESULTS: TPO + RPL group showed a higher Th17 frequency compared to healthy controls and TPO + controls groups (p = 0.0002 and p = 0.04, respectively). Additionally, mRNA expression levels of RORγT and IL-17 were significantly higher in TPO + RPL compared to healthy controls and TPO + controls groups. In contrast, Foxp3 and TGFß expression was lower in TPO + RPL. ELISA findings also indicated a significantly higher IL-17 and lower TGFß secretion in TPO + RPL compared to healthy controls and TPO + controls. Thyroid autoimmunity should intensely be controlled specially in patients with RPL history.

Lipid Profile as a Predictive Marker for Organ Dysfunction after Thoracoabdominal Surgery: A Cross-sectional Study.

Background: Plasma total cholesterol is considered a negative acute phase reactant. In various pathological conditions, such as trauma, sepsis, burns, and liver dysfunction, as well as post-surgery, serum cholesterol level decreases. This study aimed to investigate the role of lipid profiles in determining the probability of organ dysfunction after surgery. Methods: This cross-sectional study included patients who underwent thoracoabdominal surgery and were admitted to the intensive care unit of Imam Reza Hospital in Tabriz, Iran, between October 2016 and September 2018. During the first two days of admission, blood samples were taken, and serum levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), Low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and albumin were measured. The relation between the changes in these laboratory markers and six organ functions including cardiovascular, respiratory, renal, central nervous system, hepatic, and hematologic, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use were investigated. The independent t test was used to compare continuous variables. The association between different variables and organ dysfunction and mortality was evaluated by using logistic regression. Results: The serum TC increased the risk of mortality (OR=1.09, 95%CI=1.06-1.11, P<0.001), renal dysfunction (OR=1.09, 95%CI=1.06-1.12; P<0.001), liver dysfunction (OR=1.07, 95%CI=1.03-1.10; P<0.001), respiratory dysfunction (OR=1.08, 95%CI=1.05-1.13; P<0.001). Moreover, LDL, HDL, and TG were found to be inversely related to mortality, organ dysfunction, length of stay in the hospital and intensive care unit, mechanical ventilation duration, and vasopressor use. Conclusion: TC could be considered a risk factor for mortality, organ dysfunction, and clinical outcomes. On the other hand, LDL, HDL, and TG played a protective role in the patients' mortality, organ dysfunction, and clinical outcomes.

A novel portable immuno-device for the recognition of lymphatic vessel endothelial hyaluronan receptor-1 biomarker using GQD-AgNPrs conductive ink stabilized on the surface of cellulose.

Lymphatic vessel endothelium expresses various lymphatic marker molecules. LYVE-1, the lymphatic vessel endothelial hyaluronan (HA) receptor, a 322-residue protein belonging to the integral membrane glycoproteins which is found on lymph vessel wall and is completely absent from blood vessels. LYVE-1 is very effective in the passage of lymphocytes and tumor cells into the lymphatics. As regards cancer metastasis, in vitro studies indicate LYVE-1 to be involved in tumor cell adhesion. Researches show that, in neoplastic tissue, LYVE-1 is limited to the lymphovascular and could well be proper for studies of tumor lymphangiogenesis. So, the monitoring of LYVE-1 level in human biofluids has provided a valuable approach for research into tumor lymphangiogenesis. For the first time, an innovative paper-based electrochemical immune-platform was developed for recognition of LYVE-1. For this purpose, graphene quantum dots decorated silver nanoparticles nano-ink was synthesized and designed directly by writing pen-on paper technology on the surface of photographic paper. This nano-ink has a great surface area for biomarker immobilization. The prepared paper-based biosensor was so small and cheap and also has high stability and sensitivity. For the first time, biotinylated antibody of biomarker (LYVE-1) was immobilized on the surface of working electrode and utilized for the monitoring of specific antigen by simple immune-assay strategy. The designed biosensor showed two separated linear ranges in the range of 20-320 pg ml-1 and 0.625-10 pg ml-1, with the acceptable limit of detection (LOD) of 0.312 pg ml-1. Additionally, engineered immunosensor revealed excellent selectivity that promises its use in complex biological samples and assistance for biomarker-related disease screening in clinical studies.

The effect of lymphocyte immunotherapy (LIT) in modulating immune responses in patients with recurrent pregnancy loss (RPL).

In order to prevent miscarriage in RPL patients, the goal of this study was to determine how well lymphocyte immunotherapy (LIT) works in modifying immunological responses produced by cells, cytokines, transcription factors, and microRNAs. 200 RPL patients and 200 healthy controls were included in the study. Using flow cytometry, it was possible to compare the frequency of cells before and after lymphocyte treatment. Real-time PCR was used to assess the gene expression levels of transcription factors, cytokines, and microRNAs. ELISA method was used to evaluate the level of secretion of cytokines in the serum. Primary evaluation of the immune profile between healthy controls and RPL cases showed a higher frequency of Th17, NK, B cells and a lower frequency of Treg cells in RPL cases. Also, pro-inflammatory cytokines showed increased expression at mRNA and protein levels in the RPL group in comparison with the control group. Whereas, anti-inflammatory cytokines showed decreased expression in RPL patients. Decreased and increased frequency of Th17 and Treg lymphocytes observed in RPL cases following LIT, respectively. The same results obtained for RORγt and FoxP3 mRNA expression as transcription factor of Th17 and Treg cells, respectively. NK cell cytotoxicity decreased after LIT in RPL patients. miR-326a and miR-155 expression after LIT reduced, but miR-146a and miR-10a expression increased in RPL instances. LIT in RPL cases causes to elevation and modulation of anti-inflammatory and pro-inflammatory cytokines. Our data showed that lymphocyte therapy can be proposed as an effective therapeutic agent in RPL patients with immunological background by a modulating inflammatory condition.

Label-free immunosensing of telomerase using bio-conjugation of biotinylated antibody to poly(chitosan) gold nanoparticles.

Aim: This study aimed to establish a label-free electrochemical biosensor for telomerase detection in human biofluid. Method: Synthesized green nanocomposite (poly[chitosan] decorated by gold nanoparticles) was used for the efficient immobilization of biotinylated antibody of telomerase and immunocomplex of antigen-antibody. Poly(chitosan) was decorated by gold nanoparticles on the surface of a glassy carbon electrode using an electrochemical coating technique. Results: The constructed immunosensor exhibited wide dynamic range (0.078-160 IU/ml-1) with a low limit of quantification of 0.078 IU/ml-1, which present a unique manner for telomerase assays in early prognosis for cancers. Conclusion: This study encourages scientists and scholars to design and develop new biosensor platforms for point-of-care diagnostics for telomerase management, an interesting reference for future research.

Evaluation of the immune checkpoint factors in idiopathic membranous nephropathy.

Idiopathic membranous nephropathy (IMN), a single-organ autoimmune disease, is recognized by autoantibodies to podocyte proteins and identified as the most frequent cause of nephrotic syndrome in adults. T cells are important contributors in autoimmunity since they promote B-cell development, antibody production, direct inflammation, and organ tissue cytotoxicity. This study investigated the inhibitory immune checkpoint (ICP) receptors expressed on T lymphocytes and other immune cells. Thus, PBMCs from IMN patients were obtained before treatment, and the levels of ICPs such as programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated protein 4 (CTLA4), lymphocyte activation gene-3 (LAG-3), and T cell immunoglobulin-3 (TIM-3) were examined at both gene and protein expression using real time PCR and Western blot tests respectively. The results illustrated that gene expression levels of ICPs reduced significantly in comparison to the control which were verified by related fold changes of protein expression sequentially. Our study revealed that CTLA-4, PD-1, TIM-3, and LAG-3 expression is impaired in IMN patients before treatment which could be a potential target for therapy.

Observation of increased levels of autophagy-related genes and proteins in women with preeclampsia: a clinical study.

BACKGROUND: Preeclampsia is a type of pregnancy-related disease that is not fully understood underlying mechanisms of it till now. Reported results from autophagy-related studies in PE show some controversial roles of this mechanism in PE development and progression. In this study, we aimed to evaluate the autophagy process in preeclampsia women. MATERIALS AND METHODS: Peripheral blood was taken from 50 preeclampsia women and 50 healthy pregnant women. After PBMC isolation, Total RNA and total protein were extracted from PBMCs to cDNA synthesis and real-time PCR and western blotting, respectively. Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes were evaluated using real-time PCR. Atg5, beclin1, LC3B, and FOXO1 expression at the protein level was evaluated by the western blot technique. RESULTS: Real-time PCR results showed an increased expression of Atg5, Atg7, beclin1, LC3B, FOXO1, FOXO3a, FOXO4, and FOXO6 genes in PE patients compared to the healthy pregnant women and also in LOPE patients in comparison with EOPE cases. Western blotting results revealed higher expression of Atg5, beclin1, LC3B, and FOXO1 proteins in PE women compared to healthy pregnant group and in LOPE patients in comparison with EOPE cases. Our findings revealed a positive correlation between proteinuria and protein levels of Atg5, beclin1, LC3B, and FOXO1 in LOPE patients. CONCLUSION: Our investigation showed an elevated activation of autophagy in PE women in comparison with healthy pregnant women which is in controversy with some other studies. More targeted and comprehensive studies regarding the relationship of autophagy in pre-eclamptic women are needed.

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.

MicroRNA-21: A critical underestimated molecule in diabetic retinopathy.

Diabetes mellitus (DM) has grown in attention in recent years as a result of its debilitating complications and chronic disabilities. Diabetic retinopathy (DR) is a chronic microvascular complication of DM and is considered as the primary reason for blindness in adults. Early diagnosis of diabetes complications along with targeted therapy options are critical in avoiding morbidity and mortality associated with complications of diabetes. miR-21 is an important and widely studied non-coding-RNA (ncRNA) with considerable roles in various pathologic conditions including diabetic complications. miR-21 is one of the most elevated miRNAs in response to hyperglycemia and its role in angiogenesis is a major culprit of a wide range of disorders including DR. The main role of miR-21 in DR pathophysiology is believed to be through regulating angiogenesis in retina. This article aims to outline miR-21 biogenesis and distribution in human body along with discussions about its role in DR pathogenesis and its biomarker value in order to facilitate understanding of the new characteristics of miR-21 in DR management.

Dominant immune cells in pregnancy and pregnancy complications: T helper cells (TH1/TH2, TH17/Treg cells), NK cells, MDSCs, and the immune checkpoints.

Pregnancy problems including recurrent pregnancy loss, repeated implantation failure and pre-eclampsia  are common problems in the reproductive ages. Different reasons such as genetic, immunological, and environmental agents and also infections could develop these complications. In those cases in which the cause of the abortion is diagnosed, the chance of a successful pregnancy is increased by eliminating defective factors. However, in patients with unknown causes, there may be an imbalance in immune cells pattern. As a matter of fact, an inappropriate immune response is often associated with a failed pregnancy. Hence, the focus of treatment is to increase tolerance, not to suppress maternal immune system. These findings are linked to an elevated number of Treg cells and immune checkpoints through normal pregnancy. The present review discusses the balance of myeloid-derived suppressor cells, natural killer cells, T cells, and immune checkpoints, and also targeting them to maintain pregnancy and prevent associated complications.

The effect of an anti-inflammatory in comparison with a low caloric diet on physical and mental health in overweight and obese women with knee osteoarthritis: a randomized clinical trial.

PURPOSE: To evaluate the effect of an anti-inflammatory compared to a low-calorie diet on the physical and mental health of patients with knee OA. METHODS: In this randomized parallel clinical trial, participants were selected among overweight and obese women aged 40 years or older with mild to moderate OA. Sixty women with a ratio of 1:1 were randomly assigned to receive either low-calorie or anti-inflammatory accompanied by a low-calorie diet for two months. The dietary intake and weight of participants were measured. Study variables were assessed using the Western Ontario and McMaster Index (WOMAC), visual analog pain scale (VAS), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI-I), and the Short Form 36 Health Survey Questionnaire (SF-36) to indicate the quality of life (QoL). RESULTS: There was no statistically significant difference between the two groups in demographic and baseline variables except for the emotional well-being subscale of QoL. There was significant difference in anti-inflammatory compared to low-calorie diet in terms of weight (MD (95% CI): - 4.02 kg (- 6.77 to - 1.28); p = 0.005), VAS (MD (95% CI): - 0.97 (- 1.53 to - 0.41); p = 0.001), WOMAC-total score (MD (95% CI): - 9.91 (- 15.05 to - 4.78); p < 0.001), WOMAC-pain subscale (MD (95% CI): - 3.30 (- 5.30 to - 1.29); p = 0.002), WOMAC-physical function (MD(95% CI): - 5.48 (- 9.41 to - 1.53); p = 0.007), depression (p = 0.003), anxiety (p = 0.011), QoL-physical functioning (0.041), and QoL-pain (0.010) after the intervention. CONCLUSION: An anti-inflammatory accompanied by a low-calorie diet resulted in greater weight loss and greater improvement in pain intensity, functional status, depression, anxiety, and some dimension of QoL in overweight and obese women with knee OA compared to the low-calorie diet. Trial registration number and date of registration: IRCT201610220030424N2; 2018-04-23.

The impact of Hyssop (Hyssopus officinalis) extract on activation of endosomal toll like receptors and their downstream signaling pathways.

OBJECTIVES: From the ancient, medicinal benefits of Hyssop (Hyssopus officinalis L.) have been implicated for respiratory and digestive diseases despite the effects of Hyssop on viral infections have not been mechanistically investigated. In this study, we examined whether the Hyssop extract activated anti-viral innate immunity, as a sentinel for immune system, through activation of endosomal TLRs recognizing nucleic acids and their downstream signaling. The Hyssop herb extracts was prepared and co-cultured with healthy individual's peripheral blood mononuclear cells (PBMCs). After viability assay, gene expression levels of TLR3,7,8,9, as well as MyD88 and NF-κB, were evaluated in treated PBMCs using Real-time PCR. Next, the secretion level of immune related cytokines was quantified via ELISA. RESULTS: Post 24 h, 40 µg/ml of the extract significantly inhibited the viability of less than 50% of cells compared to the control and had a maximum effect on cellular function. The Hyssop-treated PBMCs demonstrated an elevated expression of endosomal TLRs genes, as well as MyD88 and NF-κB. Moreover, the release of INF-α and ß notably enhanced in cell culture supernatant, while the content of inflammatory cytokines remarkably diminished (P < 0.05). The Hyssop extract was capable of inducing antiviral innate immune responses so can be promising in antiviral drug strategies.

Hypertonic saline for traumatic brain injury: a systematic review and meta-analysis.

BACKGROUND: Traumatic brain injury (TBI) causes mortality and long-term disability among young adults and imposes a notable cost on the healthcare system. In addition to the first physical hit, secondary injury, which is associated with increased intracranial pressure (ICP), is defined as biochemical, cellular, and physiological changes after the physical injury. Mannitol and Hypertonic saline (HTS) are the treatment bases for elevated ICP in TBI. This systematic review and meta-analysis evaluates the effectiveness of HTS in the management of patients with TBI. METHODS: This study was conducted following the Joanna Briggs Institute (JBI) methods and PRISMA statement. A systematic search was performed through six databases in February 2022, to find studies that evaluated the effects of HTS, on increased ICP. Meta-analysis was performed using comprehensive meta-analysis (CMA). RESULTS: Out of 1321 results, 8 studies were included in the systematic review, and 3 of them were included in the quantitative synthesis. The results of the meta-analysis reached a 35.9% (95% CI 15.0-56.9) reduction in ICP in TBI patients receiving HTS, with no significant risk of publication bias (t-value = 0.38, df = 2, p-value = 0.73). The most common source of bias in our included studies was the transparency of blinding methods for both patients and outcome assessors. CONCLUSION: HTS can significantly reduce the ICP, which may prevent secondary injury. Also, based on the available evidence, HTS has relatively similar efficacy to Mannitol, which is considered the gold standard therapy for TBI, in boosting patients' neurological condition and reducing mortality rates.

A novel immuno-device based on the specific binding of AuNP-supported CTAB with biotinylated antibody of hyaluronic acid toward an early-stage recognition of a biomarker: a bioanalytical assay in real samples using disposal biosensor technology.

Hyaluronic Acid (HA) is a non-sulfated glycosaminoglycan, which is a potential biomarker that could be evaluated in the diagnosis of some cancers. For the first time, a novel label-free electrochemical immunosensor was developed based on modified ITO-PET (indium tin oxide-polyethylene terephthalate) electrodes for the sensitive recognition of hyaluronic acid (HA) in real samples. A disposable ITO-coated PET electrode was modified with gold nanoparticles (AuNPs) to construct a suitable substrate for the efficient immobilization of biotinylated antibodies of HA. Importantly, the encapsulation of biotinylated antibody of HA in KCC1-NH-CS2 was performed successfully, which was another innovative part of this bio-device construction. For determining the immobilization steps and optimization of the biosensor, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) techniques were used. Furthermore, the morphological characterization of each ITO electrode surface was performed by field emission scanning electron microscopy (FESEM). Specific binding of gold nanoparticles supported CTAB to ITO-PET and its bioconjugation with the biotinylated antibody of HA was studied using the electroanalysis of the sensor performance. For the better performance of the antibody to generate an immunocomplex with HA (antigen), its encapsulation was performed, which led to the excellent behavior of the immunosensor. The proposed HA immunosensor indicated excellent reproducibility, high selectivity, and long-term stability. The HA electrochemical immunosensor performed perfectly with a wide determination range (0.078 to 160 ng mL-1) and a low limit of quantification (0.078 ng mL-1) in human plasma samples. It is recommended that the designed biosensor can be used as a diagnostic tool in clinical bioassays in the near future.

Anti-thyroid antibodies and underlying generalized immunologic aberrations in patients with reproductive failures.

The link between autoimmune thyroid diseases and reproductive failures, including implantation failure and pregnancy loss, has been attracted a great deal of attention in the last two decades. In this regard, a considerable progress has been achieved in understanding the etiopathogenesis of the adverse pregnancy consequences related to the presence of anti-thyroid antibodies, however, the exact action mechanisms of these antibodies are not fully comprehended. Thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs) and TSH receptor antibodies (TRAbs) are the anti-thyroid antibodies which are present in autoimmune thyroid disorder (AITD) patients, such as Hashimoto's thyroiditis. In this condition, the thyroid hormones production, which are essential for normal implantation and pregnancy, are disrupted, and compromise the embryo or fetus development. In addition, a hypothesis suggests that there is underlying generalized immune abnormalities behind the presence of these antibodies. On the other hand, similar immunologic aberrations have been observed in thyroid autoimmunity and reproductive complications, which are postulated to be the proper answer for the scientists who seek for the pathophysiology behind the presence of these antibodies. Elevated inflammatory responses and decreased immunoregulatory actions, seem to be the main interfering pathologic factors in maternal tolerance toward fetus. In addition, cross reactivity of these antibodies with antigenic determinants of egg, embryo and placenta is another suggested mechanism, causing implantation and pregnancy complications. The ability of anti-thyroid antibodies in passing through the placental barrier and affecting the fetal thyroid gland, makes them more threatening for maintenance of a pregnancy.

SARS-CoV-2 vaccines: A double-edged sword throughout rapid evolution of COVID-19.

After more than 2 years of the coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome coronavirus 2, several questions have remained unanswered that affected our daily lives. Although substantial vaccine development could resist this challenge, emerging new variants in different countries could be considered as potent concerns regarding the adverse effects of reinfection or postvaccination. Precisely, these concerns address some significant and probable outcomes in vaccinated or reinfected models, followed by some virus challenges, such as antibody-dependent enhancement and cytokine storm. Therefore, the importance of evaluating the effectiveness of neutralizing antibodies (nAbs) elicited by vaccination and the rise of new variants must be addressed.

Platelet lysate and tendon healing: comparative analysis of autologous frozen-thawed PRP and ketorolac tromethamine in the treatment of patients with rotator cuff tendinopathy.

Platelet-rich blood derivatives are being nowadays increasingly used in the treatment of tendon-related pathologies as a rich source of growth factors. We sought to ascertain if local application of platelet lysate (PL) to augment rotator cuff repair ameliorates patient outcomes compared to ketorolac tromethamine treated group. A total of forty patients, with clinical diagnosis of Rotator Cuff Tendinopathy were randomized to receive sub acromial injections of PL every week for a total of 3 injections and two injection of ketorolac tromethamine once every two weeks. Subjective assessments included VAS, SPADI and shoulder range of motion were assessed at baseline and at 1 and 6 months after injection. Taking both control and PL groups, it was vividly seen that the outcomes were identical at the initial state, as well as the short-term one; whereas, when considering the 6-month period, there is a seemingly remarkable superiority in PL group in all parameters.

The effect of osteoporotic and non-osteoporotic individuals' T cell-derived exosomes on osteoblast cells' bone remodeling related genes expression and alkaline phosphatase activity.

OBJECTIVES: Osteoporosis is a common skeletal disorder attributed to age and is defined as a systematic degradation of bone mass and the microarchitecture leading to bone fractures. Exosomes have been reported in almost all biological fluids and during the failure of bone remodeling. 20 ml of blood samples were obtained from osteoporotic and non-osteoporotic postmenopausal women. After the isolation of peripheral blood mononuclear cells (PBMCs), T cells were separated via the magnetic-activated cell sorting (MACS) technique. Exosomes were driven from T cells of non-osteoporotic and osteoporotic volunteers. Subsequently, normal osteoblasts were treated with obtained T cell exosomes to assess osteoblastic function and gene expression. RESULTS: Runx2, type I collagen, osteopontin, and osteocalcin expression decreased in osteoblasts treated by osteoporotic T cell exosomes. In contrast, an increased expression of the mentioned genes was observed following non-osteoporotic T cell exosome treatment. Additionally, osteoblast alkaline phosphatase (ALP) activity treated with non-osteoporotic T cell exosomes increased. However, this activity decreased in another group. Our data demonstrated that T cell exosomes obtained from osteoporotic and non-osteoporotic individuals could alter the osteoblastic function and gene expression by affecting the genes essential for bone remodeling.

Expression level of immune checkpoint inhibitory factors in preeclampsia.

Preeclampsia (PE) is a severe complication in pregnancy, and its symptoms (proteinuria and hypertension) manifest after 20 weeks of gestation, affecting up to 8 % of pregnancies. The pregnant women's immune system uses different tolerance mechanisms to deal with a semi-allogeneic fetus. The T-cell subsets including CD8+, CD4+, and Treg play a critical role in maintaining pregnancies. The expression of immune checkpoint molecules in T-cells can ensure pregnancy at the feto-maternal interface by controlling immune responses. This research aims to evaluate the expression level of immune checkpoint factors, including PD-1, LAG-3, CTLA-4, and TIM-3 in normal pregnant women and PE patients. Decidual tissue was collected from 50 participants (25 PE and 25 control). For evaluating the genes expression, real-time PCR was employed. The western blot was used to assess the proteins level. The results of real-time PCR indicated significantly decreased expression level of these immune checkpoints in PE patients. In parallel to gene expression results, the protein level of PD-1, LAG-3, CTLA-4, and TIM-3 in the PE group was also reduced. We revealed that the profile of proteins and genes expression of immune checkpoints in the decidua of PE mothers are different from normal pregnancy and these results indicate aberrant expression of immune checkpoints such as PD-1, LAG-3, CTLA-4, and TIM-3 may cause maladaptation immune response which results in PE manifestation.