Therapeutic approaches in patients with β-thalassemia

Beta-thalassemia (β-thal) is a congenital hemoglobinopathy explained by a decreased level (β+) or absence (βο) of β-globin gene expression. Microcytic hypochromic anemia and various clinical symptoms comprising severe anemia to clinically nonsymptomatic features. Treatment with an ordered blood transfusion and iron chelator agents can decrease transfusion iron overload that causes normal maturation. These patients also are at high risk for secondary iron overload because of erythropheron (GF15–TWSG1) release from erythroblasts resulting in erythroid hyperplasia. Based on the previous studies, chemicals such as hydroxyurea and 5-azacytidine are useful in treating β-hemoglobinopathy, including β-thal and sickle cell disease (SCD). Regarding both side effects and lifelong treatment of these chemical components, researchers have recently regarded gene-based treatments. These techniques, such as micro RNA gene silencing, viral-mediated gene editing, and clustered regulatory interspaced short palindromic repeats (CRISPR)-CAS9 systems, are the most commonly used gene therapy methods. Nowadays, ɣ-globin (fetal globin) gene reactivation is one of the most popular treatments for β-thal. Researches showed that these gene modification methods for γ-globin gene reactivation are also useful in increasing hemoglobin F (HbF) and helping patients with β-thal. In this review study, new therapeutic approaches to manage this disorder are regarded.

Chronic loneliness: neurocognitive mechanisms and interventions

Loneliness has been associated with detrimental effects on mental and physical health and is increasingly recognized as a critical public health issue which may be further exacerbated by societal challenges such as increasing urbanization, an aging society as well as the COVID-19 pandemic. We here review recent findings on the neurocognitive mechanisms and brain alterations that underpin social disconnectedness, therapeutic approaches for chronic loneliness and how these lines of research can be integrated to improve the efficacy of loneliness interventions in healthy individuals and patients with mental disorders.

Case Report: Recurrence of Testicular Myofibroblastic Tumor After Surgery

Inflammatory myofibroblastic tumour (IMT), also known as plasma cell granuloma (PCG) or inflammatory pseudotumour (IPT), is a distinctive, rarely metastasizing neoplasm composed of myofibroblastic and fibroblastic spindle cells accompanied by inflammatory infiltration of plasma cells, lymphocytes and/or eosinophils. IMT predominantly affects children and young adults, and the age at presentation ranges from 3 to 89 years. We present a very rare case of recurrent testicular IMT without ALK rearrangement. This case highlights the clinical characteristics and diagnostic factors associated with primary and recurrent foci of this rare tumour, along with key therapeutic approaches.

Structure and function of a family of tick-derived complement inhibitors targeting properdin

Activation of the serum-resident complement system begins a cascade that leads to activation of membrane-resident complement receptors on immune cells, thus coordinating serum and cellular immune responses. Whilst many molecules act to control inappropriate activation, Properdin is the only known positive regulator of the human complement system. By stabilising the alternative pathway C3 convertase it promotes complement self-amplification and persistent activation boosting the magnitude of the serum complement response by all triggers. In this work, we identify a family of tick-derived alternative pathway complement inhibitors, hereafter termed CirpA. Functional and structural characterisation reveals that members of the CirpA family directly bind to properdin, inhibiting its ability to promote complement activation, and leading to potent inhibition of the complement response in a species specific manner. We provide a full functional and structural characterisation of a properdin inhibitor, opening avenues for future therapeutic approaches.

Overview of the pre-clinical and clinical studies about the use of CAR-T cell therapy of cancer combined with oncolytic viruses

Background Cancer is one of the critical issues of the global health system with a high mortality rate even with the available therapies, so using novel therapeutic approaches to reduce the mortality rate and increase the quality of life is sensed more than ever. Main body CAR-T cell therapy and oncolytic viruses are innovative cancer therapeutic approaches with fewer complications than common treatments such as chemotherapy and radiotherapy and significantly improve the quality of life. Oncolytic viruses can selectively proliferate in the cancer cells and destroy them. The specificity of oncolytic viruses potentially maintains the normal cells and tissues intact. T-cells are genetically manipulated and armed against the specific antigens of the tumor cells in CAR-T cell therapy. Eventually, they are returned to the body and act against the tumor cells. Nowadays, virology and oncology researchers intend to improve the efficacy of immunotherapy by utilizing CAR-T cells in combination with oncolytic viruses. Conclusion Using CAR-T cells along with oncolytic viruses can enhance the efficacy of CAR-T cell therapy in destroying the solid tumors, increasing the permeability of the tumor cells for T-cells, reducing the disturbing effects of the immune system, and increasing the success chance in the treatment of this hazardous disease. In recent years, significant progress has been achieved in using oncolytic viruses alone and in combination with other therapeutic approaches such as CAR-T cell therapy in pre-clinical and clinical investigations. This principle necessitates a deeper consideration of these treatment strategies. This review intends to curtly investigate each of these therapeutic methods, lonely and in combination form. We will also point to the pre-clinical and clinical studies about the use of CAR-T cell therapy combined with oncolytic viruses.

Potential therapeutic options for COVID-19: an update on current evidence

SARS-CoV-2, a novel coronavirus, is the agent responsible for the COVID-19 pandemic and is a major public health concern nowadays. The rapid and global spread of this coronavirus leads to an increase in hospitalizations and thousands of deaths in many countries. To date, great efforts have been made worldwide for the efficient management of this crisis, but there is still no effective and specific treatment for COVID-19. The primary therapies to treat the disease are antivirals, anti-inflammatories and respiratory therapy. In addition, antibody therapies currently have been a many active and essential part of SARS-CoV-2 infection treatment. Ongoing trials are proposed different therapeutic options including various drugs, convalescent plasma therapy, monoclonal antibodies, immunoglobulin therapy, and cell therapy. The present study summarized current evidence of these therapeutic approaches to assess their efficacy and safety for COVID-19 treatment. We tried to provide comprehensive information about the available potential therapeutic approaches against COVID-19 to support researchers and physicians in any current and future progress in treating COVID-19 patients.

Emerging Role of LncRNA Regulation for NLRP3 Inflammasome in Diabetes Complications

Diabetes is a widespread metabolic disease with various complications, including diabetic nephropathy, retinopathy, cardiomyopathy, and other cardiovascular or cerebrovascular diseases. As the prevalence of diabetes increases in all age groups worldwide, diabetes and its complications cause an emerging public health burden. NLRP3 inflammasome is a complex of several proteins that play a critical role in inflammatory response and various diseases, including diabetes and its complications. Accumulating evidences indicate that NLRP3 inflammasome contributes to the development of diabetes and diabetic complications and that NLRP3 inflammation inactivation is beneficial in treating these illnesses. Emerging evidences suggest the critical role of long non-coding RNAs (lncRNAs) in regulating NLRP3 inflammasome activity in various diseases. LncRNAs are non-coding RNAs exceeding 200 nucleotides in length. Its dysregulation has been linked to the development of diseases, including diabetes. Recently, growing evidences hint that regulating lncRNAs on NLRP3 inflammasome is critical in developing and progressing diabetes and diabetic complications. Here, we discuss the role of lncRNAs in regulating NLRP3 inflammasome as well as its participation in diabetes and diabetic complications, providing novel insights into developing future therapeutic approaches for diabetes.

Differences and Similarities in Motives to Decrease Drinking, and to Drink in General Between Former and Current Heavy Drinkers—Implications for Changing Own Drinking Behaviour

The evidence on why people initiate or cease drinking is vast; however, little is known regarding why people change their frequency and amount of drinking from intense (heavy or dependent drinking) to recreational (with little risk). Therefore, the purpose of this study was to investigate how drinking motives and motives to decrease drinking differ between former heavy drinkers (problematic and dependent), current dependent, and current recreational drinkers. Data were obtained from four groups of individuals (n = 263) using alcohol with different severity. The participants were Polish young adults aged between 18 and 35 years. About 53% of the sample were women. The Alcohol Use Disorder Identification Test (AUDIT) was used to assess the level of drinking; the Drinking Motive Questionnaire-Revised Short Form (DMQ-R SF) was used to assess drinking motives (social, coping, enhancement, and conformity). The reasons for abstaining and limiting drinking (RALD) instrument was used to assess the RALD. Additionally, a set of questions regarding motives to decrease drinking were analysed. The results show that differences were observed between the investigated groups: the current dependent group scored significantly higher on all the dimensions of drinking motives than the current low-risk group and significantly higher on coping, social, and enhancement motives than former heavy drinkers (both groups). The two groups of former heavy drinkers did not differ from each other on drinking motives. The investigated groups differed on the motives to reduce drinking—low-risk users scored the lowest on all the motives, whereas current dependent—the highest. The differences in motives to decrease drinking between current-depended and former heavy drinkers indicate which motives can be associated with the prevention strategies, programmes, and therapeutic approaches.

Induction and Maintenance Treatment of Lupus Nephritis: A Comprehensive Review of Meta-Analyses

Background: Lupus nephritis (LN) is present in over 50% of patients with systemic lupus erythematosus (SLE) which is managed with immunosuppressive and immunomodulatory therapies. However, several novel therapeutic approaches for LN are under investigation due to the adverse effects spectrum of conventional therapy; Methods: We performed a comprehensive review of meta-analyses aggregating the comparative efficacies of various pharmacotherapies for LN. We conducted a literature search and retrieved a total of 23 meta-analyses and network meta-analyses for summarization. Pharmacotherapies were evaluated across six major outcomes: remission, relapse, mortality, end stage kidney disease (ESKD) progression, infection, and malignancy. Result: Calcineurin inhibitors (CNI), particularly tacrolimus (TAC), in combination with glucocorticoids (GC) outperformed cyclophosphamide (CPA) with GC in the rate of remission, either complete or partial remission, and in terms of infectious complications. In maintenance therapy, MMF was superior to azathioprine (AZA) as the MMF-treated patients had lower relapse rate. Interpretation: This review aggregates evidence of therapy for clinicians and sheds light on comparative efficacies of alternative LN treatments. As more promising agents are entering the market, such as voclosporin, belimumab, and obinutuzumab, LN management might undergo significant changes during the next years.