Regulatory NK cells in autoimmune disease

NK cells are defined as the major components of the immunological network which exerts defense against tumors and viral infections as well as regulation of innate and adaptive immunity, shaped through interaction with other cells like T cells. According to the surface markers, NK cells can be divided into CD56dim NK and CD56bright NK subsets. CD56bright NK cells usually are known as regulatory NK cells. Once the immune system loses its self-tolerance, autoimmune diseases develop. NK cells and their subsets can be altered during autoimmune diseases, indicative of their prominent regulatory roles and even pathological and protective functions in autoimmune disorders. In this regard, activation of CD56bright NK cells can suppress activated autologous CD4+ T cells and subsequently prevent the initiation of autoimmunity. In this review article, we summarize the roles of regulatory NK cells in autoimmune disease occurrence which needs more research to uncover their exact related mechanism. It seems that targeting NK cells can be a promising therapeutic platform against autoimmune diseases

Proinflammatory Activation of Osteoclasts Due to High Prolactin Level

High concentrations of prolactin (PRL) during the lactation period have an essential role in milk production by mammary glands stimulation. PRL may have an impact on calcium regulation and bone mineral density. We investigated if the PRL concentration during the lactation period could influence osteoclast (OC) activation and bone mineral density (BMD). In vivo, the Calcium Detection Assay, and ELISA were used to detect serum calcium, PRL, and inflammatory cytokines, respectively. BMD was evaluated by µ-CT in six months old female mice during lactation. The osteoclast (OC) activity was detected by Tartrate-resistant acid phosphatase (TRAP), Immunohistochemistry (IHC), and hematoxylin and eosin (H&E). In vitro, osteoclast differentiation, resorption and their activity markers TRAP, Matrix metallopeptidase 9 (MMP-9), Cathepsin K (CTSK), C-reactive protein (CRP), Receptor activator of nuclear factor kappa-Β (RANK) and inflammatory cytokines were measured in osteoclasts stimulated with recombinant prolactin protein (rPRL) or with an anti-prolactin blocker. We found that serum calcium, PRL, and inflammatory markers were increased. BMD was significantly reduced in lactating mice; TRAP activity was increased and tubercular was reduced in lactating mice compared to normal mice. In vitro, the osteoclast number, resorption, and activation markers TRAP, MMP-9, CTSK, CRP, and RANK were significantly increased after treatment with rPRL protein, but not in osteoclasts treated with anti-prolactin receptor antibody and rPRL. The gene expression of TNF-α, IL-6, and Monocyte chemoattractant protein-1 (MCP-1) but not IL-1b were significantly increased in osteoclasts with PRL treatment compared to the untreated osteoclasts. Taken together, the high level of PRL could activate osteoclasts and proinflammatory cytokines expression which reduce BMD in the lactation period

Assessment of COVID-19 vaccination among healthcare workers in Iraq; adverse effects and hesitancy

Several messenger ribonucleic acid (mRNA) and inactivated COVID-19 vaccines are available to the global population as of 2022. The acceptance of the COVID-19 vaccine will play a key role in combating the worldwide pandemic. Public confidence in this vaccine is largely based on its safety and effectiveness. This study was designed to provide independent evidence of the adverse effects associated with COVID-19 vaccines among healthcare workers in Iraq and to identify the attitudes of healthcare workers who rejected the vaccination. We conducted a cross-sectional study to collect data on the adverse effects of the Pfizer, AstraZeneca, and Sinopharm vaccines. Data were collected between October 2021 and February 2022. A total of 2,202 participants were enrolled in the study: (89.97%) received injections of the COVID-19 vaccines and (10.03%) were hesitant to receive the vaccination. Participants received either the Pfizer vaccine (62.9%), AstraZeneca vaccine (23.5%) or Sinopharm vaccine (13.6%). Most adverse effects were significantly less prevalent in the second dose than in the first dose. Notably, the adverse effects associated with the Pfizer vaccine were significantly more prevalent in females than in males. Following the first dose, the participants experienced more adverse effects with the AstraZeneca vaccine. Following the second dose, more adverse effects were associated with the Pfizer vaccine. Interestingly, the prevalence of COVID-19 infection in participants who received two doses of the Pfizer vaccine was significantly reduced compared to those who received two doses of either the AstraZeneca or Sinopharm vaccines. According to vaccine-hesitated participants, insufficient knowledge (29.9%), expeditious development (27.6%) and lack of trust in the vaccines (27.1%) were the three major reasons for refusing the vaccines. The results of our study indicated that these adverse effects do not present a significant problem and should not prevent successful control of the COVID-19 pandemic

Immune modulation in the prevention of pathologies relating to diet-induced obesity

Non-alcoholic fatty liver disease (NAFLD) results from accumulation of fat in liver, so-called steatosis. Fatty liver may lead to the development of inflammation (steatohepatitis). This study analysed the role of high fat diet, Vitamin D, and complement properdin in mouse models of high fat diet. Properdin knockout mice, and properdin wild type mice on LDLR-/- and LDLR+/+ background were fed a high fat –high sugar diet or Western (high fat) diet. Body weight, fat pad weight, liver histopathology, immunohistochemistry were analysed. Hepatic expression of candidate genes (TNF-α, srebp-1c, TLR4, HMGCR, SR-B1, PPAR-y) was performed by qPCR. ELISA was used to quantify serum insulin, Adiponectin, MDA. Liver function test, endotoxin, complement activation, Western blot were evaluated. in vivo results showed that a high fat–high sugar diet and so-called Western diet led to the development steatosis, inflammation, and properdin has a role in the prevention of obesity, and metabolic syndrome diseases. Vitamin D given to mice fed high fat –high sugar diet led to the prevention of obesity, and associated complications. Exercising mice combined with supplemented Vitamin D had a better effect to prevent metabolic syndrome diseases. in vitro results shown that DHA, Vitamin D, and Allicin had anti-inflammatory roles by reducing TNF-α to LPS stimulation

Complement Properdin Regulates the MetaboloInflammatory Response to a High Fat Diet

open access articleBackground and objectives: Overnutrition leads to a metabolic and inflammatory response that includes the activation of Complement. Properdin is the only amplifier of complement activation and increases the provision of complement activation products. Its absence has previously been shown to lead to increased obesity in mice on a high fat diet. The aim of this study was to determine ways in which properdin contributes to a less pronounced obese phenotype. Materials and Methods: Wild type (WT) and properdin deficient mice (KO) were fed a high-fat diet (HFD) for up to 12 weeks. Results: There was a significant increase in liver triglyceride content in the KO HFD group compared to WT on HFD. WT developed steatosis. KO had an additional inflammatory component (steatohepatitis). Analysis of AKT signalling by phosphorylation array supported a decrease in insulin sensitivity which was greater for KO than WT in liver and kidney. There was a significant decrease of C5L2 in the fat membranes of the KO HFD group compared to the WT HFD group. Circulating microparticles in KO HFD group showed lower presence of C5L2. Expression of the fatty acid transporter CD36 in adipose tissue was increased in KO on HFD and was also significantly increased in plasma of KO HFD mice compared to WT on HFD. CD36 was elevated on microparticles from KO on HFD. Ultrastructural changes consistent with obesity associated glomerulopathy were observed for both HFD fed genotypes, but tubular strain was greater in KO. Conclusion: Our work demonstrates that complement properdin is a dominant factor in limiting the severity of obesity-associated conditions that impact on liver and kidney. The two receptors, C5L2 and CD36, are downstream of the activity exerted by properdin

Immunoglobulin A response to SARS-CoV-2 infection and immunity

The novel coronavirus disease (COVID-19) and its infamous “Variants” of the etiological agent termed Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) has proven to be a global health concern. The three antibodies, IgA, IgM, and IgG, perform their dedicated role as main workhorses of the host adaptive immune system in virus neutralization. Immunoglobulin-A (IgA), also known as “Mucosal Immunoglobulin”, has been under keen interest throughout the viral infection cycle. Its importance lies because IgA is predominant mucosal antibody and SARS family viruses primarily infect the mucosal surfaces of human respiratory tract. Therefore, IgA can be considered a diagnostic and prognostic marker and an active infection biomarker for SARS CoV-2 infection. Along with molecular analyses, serological tests, including IgA detection tests, are gaining ground in application as an early detectable marker and as a minimally invasive detection strategy. In the current review, it was emphasized the role of IgA response in diagnosis, host defense strategies, treatment, and prevention of SARS-CoV-2 infection. The data analysis was performed through almost 100 published peer-reviewed research reports and comprehended the importance of IgA in antiviral immunity against SARS-CoV-2 and other related respiratory viruses. Taken together, it is concluded that secretory IgA- Abs can serve as a promising detection tool for respiratory viral diagnosis and treatment parallel to IgG-based therapeutics and diagnostics. Vaccine candidates that target and trigger mucosal immune response may also be employed in future dimensions of research against other respiratory viruses

Functional interplay between long non-coding RNAs and Breast CSCs

Abstract Breast cancer (BC) represents aggressive cancer affecting most women’s lives globally. Metastasis and recurrence are the two most common factors in a breast cancer patient's poor prognosis. Cancer stem cells (CSCs) are tumor cells that are able to self-renew and differentiate, which is a significant factor in metastasis and recurrence of cancer. Long non-coding RNAs (lncRNAs) describe a group of RNAs that are longer than 200 nucleotides and do not have the ability to code for proteins. Some of these lncRNAs can be mainly produced in various tissues and tumor forms. In the development and spread of malignancies, lncRNAs have a significant role in influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic and prognostic markers in treating the disease and guiding clinical therapy. However, it is not well known how the interaction of lncRNAs with CSCs will affect cancer development and progression. Here, in this review, we attempt to summarize recent findings that focus on lncRNAs affect cancer stem cell self-renewal and differentiation in breast cancer development and progression, as well as the strategies and challenges for overcoming lncRNA's therapeutic resistance