Evaluation of IP3R3 Gene Silencing Effect on Pyruvate Dehydrogenase (PDH) Enzyme Activity in Breast Cancer Cells with and Without Estrogen Receptor.

Background: Inositol 1,4,5-trisphosphate receptor (IP3R), a critical calcium ion (Ca2+) regulator, plays a vital role in breast cancer (BC) metabolism. Dysregulated IP3R in BC cells can drive abnormal growth or cell death. Estradiol increases IP3R type 3 (IP3R3) levels in BC, promoting cell proliferation and metabolic changes, including enhanced pyruvate dehydrogenase (PDH) activity, which, when reduced, leads to cell apoptosis. The study silenced IP3R3 to assess its impact on PDH. Materials and Methods: The study used IP3R3 small interfering RNA (siRNA) to target Michigan Cancer Foundation-7 (MCF-7) and MDA-MB-231 cell lines. Transfection success was confirmed by flow cytometry. Cell viability and gene silencing were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and real-time quantitative polymerase chain reaction (PCR) assays. Protein expression and cellular activity were analyzed through western blotting and PDH activity measurement. Results: Transfecting MCF-7 and MDA-MB-231 cells with IP3R3 siRNA achieved a 65% transfection rate without significant toxicity. IP3R3 gene silencing effectively reduced IP3R3 messenger RNA (mRNA) and protein levels in both cell lines, leading to decreased PDH enzyme activity, especially in MDA-MB-231 cells. Conclusion: The study highlights a link between high IP3R3 gene silencing and reduced PDH activity, with higher IP3R3 expression in estrogen-independent (MDA-MB-231) compared to estrogen-dependent (MCF-7) cell lines. This suggests a potential impact on BC metabolism and tumor growth via regulation of PDH activity.

Smart co-delivery of plasmid DNA and doxorubicin using MCM-chitosan-PEG polymerization functionalized with MUC-1 aptamer against breast cancer.

This study introduces an innovative co-delivery approach using the MCM-co-polymerized nanosystem, integrating chitosan and polyethylene glycol, and targeted by the MUC-1 aptamer (MCM@CS@PEG-APT). This system enables simultaneous delivery of the GFP plasmid and doxorubicin (DOX). The synthesis of the nanosystem was thoroughly characterized at each step, including FTIR, XRD, BET, DLS, FE-SEM, and HRTEM analyses. The impact of individual polymers (chitosan and PEG) on payload retardation was compared to the co-polymerized MCM@CS@PEG conjugation. Furthermore, the DOX release mechanism was investigated using various kinetic models. The nanosystem's potential for delivering GFP plasmid and DOX separately and simultaneously was assessed through fluorescence microscopy and flow cytometry. The co-polymerized nanosystem exhibited superior payload entrapment (1:100 ratio of Plasmid:NPs) compared to separately polymer-coated counterparts (1:640 ratio of Plasmid:NPs). Besides, the presence of pH-sensitive chitosan creates a smart nanosystem for efficient DOX and GFP plasmid delivery into tumor cells, along with a Higuchi model pattern for drug release. Toxicity assessments against breast tumor cells also indicated reduced off-target effects compared to pure DOX, introducing it as a promising candidate for targeted cancer therapy. Cellular uptake findings demonstrated the nanosystem's ability to deliver GFP plasmid and DOX separately into MCF-7 cells, with rates of 32% and 98%, respectively. Flow cytometry results confirmed efficient co-delivery, with 42.7% of cells showing the presence of both GFP-plasmid and DOX, while 52.2% exclusively contained DOX. Overall, our study explores the co-delivery potential of the MCM@CS@PEG-APT nanosystem in breast cancer therapy. This system's ability to co-deliver multiple agents preciselyopens new avenues for targeted therapeutic strategies.

A qualitative report on experiences of participants in the young innovative leadership program.

BACKGROUND: Leadership in health system is a universal challenge. The Young Innovative Leadership Program (YILP) designed for undergraduate and postgraduate medical sciences students, implemented at the Isfahan University of Medical Sciences, aimed to cultivate leadership capacities through a 16-week training program. This program comprises ten modules covering innovation, change leadership, and management skills, with mentor-facilitated group discussions. This study aimed to provide a qualitative report of the experiences of participants in the YILP. METHODS: A qualitative study was conducted in 2022, three months after the end of the training program, to investigate the participants' perspectives. Data was extracted through in-depth, semi-structured interviews with 14 participants. RESULTS: In this study 14 undergraduate and postgraduate medical sciences students who had participated in the YILP the previous year were included. Four main categories emerged from the interviews: "emergence of new horizons", "values as beacon", "an expanded toolbox", and "program's structure: a learning atmosphere". CONCLUSIONS: The results of our study indicated that medical science students would benefit from leadership development programs. In this regard, the framework utilized to implement YILP could serve as a role model.

Co-release of nitric oxide and L-arginine from poly (ß-amino ester)-based adhesive reprogram macrophages for accelerated wound healing and angiogenesis in vitro and in vivo.

Recently, insufficient angiogenesis and prolonged inflammation are crucial challenges of chronic skin wound healing. The sustained release of L-Arginine (L-Arg) and nitric oxide (NO) production can control immune responses, improve angiogenesis, enhance re-epithelialization, and accelerate wound healing. Here, we aim to improve wound healing via the controlled release of NO and L-Arg from poly (ß-amino ester) (PßAE). In this regard, PßAE is functionalized with methacrylate poly-L-Arg (PAMA), and the role of PAMA content (50, 66, and 75 wt%) on the adhesive properties, L-Arg, and NO release, as well as collagen deposition, inflammatory responses, and angiogenesis, is investigated in vitro and in vivo. Results show that the PAMA/ PßAE could provide suitable adhesive strength (~25 kPa) for wound healing application. In addition, increasing the PAMA content from 50 to 75 wt% results in an increased release of L-Arg (approximately 1.4-1.7 times) and enhanced NO production (approximately 2 times), promoting skin cell proliferation and migration. The in vitro studies also show that compared to PßAE hydrogel, incorporation of 66 wt% PAMA (PAMA 66 sample) reveals superior collagen I synthesis (~ 3-4 times) of fibroblasts, controlled pro-inflammatory and improved anti-inflammatory cytokines secretion of macrophages, and accelerated angiogenesis (~1.5-2 times). In vivo studies in a rat model with a full-thickness skin defect also demonstrate the PAMA66 sample could accelerate wound healing (~98 %) and angiogenesis, compared to control (untreated wound) and Tegaderm™ commercial wound dressing. In summary, the engineered multifunctional PAMA functionalized PßAE hydrogel with desired NO and L-Arg release, and adhesive properties can potentially reprogram macrophages and accelerate skin healing for chronic wound healing.

The Cytotoxicity of 27-Hydroxycholesterol in MCF-7 and MDA-MB-231.

Background: Although several roles of 27-hydroxycholesterol (27-HC), the most abundant oxysterol in blood circulation, in cancers have been elucidated, its impact on breast cancer proliferation and its pathway remain unknown. Materials and Methods: The effect of 27-HC on breast cancer cell proliferation and its pathway was evaluated using Michigan Cancer Foundation - 7 (MCF-7) and M.D. Anderson - Metastatic Breast 231 (MDA-MB-231) cell lines. The MTT assay was applied after 24- and 48-hour incubation to distinguish cell proliferation. To determine the cause of different viability results from the MTT assay, the Annexin-FITC/PI test was used at concentrations of 0.1, 1, and 10 µM after 24- and 48-hour incubation. Results: 27-HC in concentrations of 5, 10, and 20 µM induced cell cytotoxicity compared with control. Also, the annexin V conjugated with fluorescein isothiocyanate/propidium iodide (Annexin-FITC/PI) test revealed an increase in total apoptotic cells treated with 0.1, 1, and 10 µM of 27-HC after 48 hours (P value < 0.05). Besides, the cytotoxic effect of 27-HC was observed at 10 µM concentration in both cell lines, MCF-7 and MDA-MB-231 (P value < 0.05). Conclusion: The identification of 27-HC's cytotoxic effects on both estrogen receptor (ER)-negative and ER-positive breast cancer cell lines is a novel discovery that may be linked to LXRß.

The nexus of natural killer cells and melanoma tumor microenvironment: crosstalk, chemotherapeutic potential, and innovative NK cell-based therapeutic strategies.

The metastasis of melanoma cells to regional lymph nodes and distant sites is an important contributor to cancer-related morbidity and mortality among patients with melanoma. This intricate process entails dynamic interactions involving tumor cells, cellular constituents, and non-cellular elements within the microenvironment. Moreover, both microenvironmental and systemic factors regulate the metastatic progression. Central to immunosurveillance for tumor cells are natural killer (NK) cells, prominent effectors of the innate immune system with potent antitumor and antimetastatic capabilities. Recognizing their pivotal role, contemporary immunotherapeutic strategies are actively integrating NK cells to combat metastatic tumors. Thus, a meticulous exploration of the interplay between metastatic melanoma and NK cells along the metastatic cascade is important. Given the critical involvement of NK cells within the melanoma tumor microenvironment, this comprehensive review illuminates the intricate relationship between components of the melanoma tumor microenvironment and NK cells, delineating their multifaceted roles. By shedding light on these critical aspects, this review advocates for a deeper understanding of NK cell dynamics within the melanoma context, driving forward transformative strategies to combat this cancer.

The effects of ALK5 inhibition and simultaneous inhibition or activation of HIF-1α in melanoma tumor growth and angiogenesis.

BACKGROUND: Hypoxia is the most common signature of the tumor microenvironment that drives tumorigenesis through the complex crosstalk of a family of transcription factors called hypoxia-inducible factors (HIFs), with other intercellular signaling networks. Hypoxia increases transforming growth factor-beta (TGF-ß) expression. TGF-ß and HIF-1α play critical roles in several malignancies and their interactions in melanoma progression remain unknown. Therefore, the aim of this study was to assess the impact of inhibiting activin receptor-like kinase-5 (ALK5), a TGF-ß receptor, on the response to HIF-1α activation or inhibition in melanoma tumor progression. MATERIALS AND METHODS: Tumors were induced in C57BL/6J mice by subcutaneous inoculation with B16F10 melanoma cells. Mice were divided into HIF-1α inhibitor, ALK5 inhibitor (1 mg/kg) and HIF-1α inhibitor (100 mg/kg), ALK5 inhibitor, HIF-1α activator (1000 mg/kg), HIF-1α activator and ALK5 inhibitor, and control groups to receive inhibitors and activators through intraperitoneal injection. The expression of E-cadherin was evaluated by RT-qPCR. Vessel density and platelet-derived growth factor receptor beta (PDGFR)-ß+ cells around the vessels were investigated using immunohistochemistry. RESULTS: The groups receiving HIF-1α inhibitor and activator showed lower and higher tumor growth compared to the control group, respectively. E-cadherin expression decreased in all groups compared to the control group, illustrating the dual function of E-cadherin in the tumor microenvironment. Vascular density was reduced in the groups given HIF-1α inhibitor, ALK5 inhibitor, and ALK5 and HIF-1α inhibitor simultaneously. The percentage of PDGFR-ß+ cells was reduced in the presence of HIF-1α inhibitor, ALK5 inhibitor, HIF-1α and ALK5 inhibitors, and upon simultaneous treatment with HIF-1α activator and ALK5 inhibitor. CONCLUSION: Despite increased expression and interaction between TGF-ß and HIF-1α pathways in some cancers, in melanoma, inhibition of either pathway alone may have a stronger effect on tumor inhibition than simultaneous inhibition of both pathways. The synergistic effects may be context-dependent and should be further evaluated in different cancer types.

Multiple sclerosis is associated with worse COVID-19 outcomes compared to the general population: A population-based study.

BACKGROUND: We carried out the current study to compare COVID-19-related hospitalization and mortality rates between people living with multiple sclerosis (PLWMS) and MS-free controls from the Isfahan general population. METHOD: In this retrospective population-based study, we used available data from four datasets of Isfahan University of Medical Sciences from January 1, 2020, to August 22, 2021. Data on all PLWMS, SARS-CoV-2 polymerase chain reaction (PCR) and rapid antigen test, hospitalization, and death were included. We compared the odds of COVID-19-related hospitalization and mortality between PLWMS and the control group before and after adjustment for age and sex. We categorized all people into young (18-49 years) and old age (50-79 years) groups and compared the hospitalization rate between people with and without MS. RESULTS: In total, 829 PLWMS and 2494 MS-free controls with confirmed COVID-19 were included. Hospitalization rates among PLWMS and MS-free controls were 16.2% and 16.5% (crude OR= 0.978, 95%CI: 0.79, 1.21). In the adjusted model, PLWMS with COVID-19 had 56% increased odds of hospitalization (OR=1.56, 95%CI: 1.23, 1.97). During follow-up, there were 11 (1.3%) and 49 (2%) COVID-19-related deaths among PLWMS and MS-free controls, respectively. No significant difference between people with and without MS in COVID-19-related mortality rate was observed (crude OR= 0.678, 95%CI: 0.351, 1.31; adjusted OR=2.013, 95%CI: 0.95, 4.26). We found increased odds of hospitalization in young PLWMS compared to those without MS at the same age (OR=1.699, 95%CI: 1.289, 2.240). But, no difference between older people with and without MS was detected (OR=1.005, 95%CI: 0.662, 1.524). CONCLUSION: This study revealed higher odds of hospitalization and mortality due to COVID-19 among PLWMS in comparison to age- and sex-matched controls from the general population. Nevertheless, it remains unclear whether the elevated odds are directly associated with MS itself or if they are influenced by factors such as rituximab using, comorbidity, and disease severity.

Microfluidic-based technologies in cancer liquid biopsy: Unveiling the role of horizontal gene transfer (HGT) materials.

Liquid biopsy includes the isolating and analysis of non-solid biological samples enables us to find new ways for molecular profiling, prognostic assessment, and better therapeutic decision-making in cancer patients. Despite the conventional theory of tumor development, a non-vertical transmission of DNA has been reported among cancer cells and between cancer and normal cells. The phenomenon referred to as horizontal gene transfer (HGT) has the ability to amplify the advancement of tumors by disseminating genes that encode molecules conferring benefits to the survival or metastasis of cancer cells. Currently, common liquid biopsy approaches include the analysis of extracellular vesicles (EVs) and tumor-free DNA (tfDNA) derived from primary tumors and their metastatic sites, which are well-known HGT mediators in cancer cells. Current technological and molecular advances expedited the high-throughput and high-sensitive HGT materials analyses by using new technologies, such as microfluidics in liquid biopsies. This review delves into the convergence of microfluidic-based technologies and the investigation of Horizontal Gene Transfer (HGT) materials in cancer liquid biopsy. The integration of microfluidics offers unprecedented advantages such as high sensitivity, rapid analysis, and the ability to analyze rare cell populations. These attributes are instrumental in detecting and characterizing CTCs, circulating nucleic acids, and EVs, which are carriers of genetic cargo that could potentially undergo HGT. The phenomenon of HGT in cancer has raised intriguing questions about its role in driving genomic diversity and acquired drug resistance. By leveraging microfluidic platforms, researchers have been able to capture and analyze individual cells or genetic material with enhanced precision, shedding light on the potential transfer of genetic material between cancer cells and surrounding stromal cells. Furthermore, the application of microfluidics in single-cell sequencing has enabled the elucidation of the genetic changes associated with HGT events, providing insights into the evolution of tumor genomes. This review also discusses the challenges and opportunities in studying HGT materials using microfluidic-based technologies. In conclusion, microfluidic-based technologies have significantly advanced the field of cancer liquid biopsy, enabling the sensitive and accurate detection of HGT materials. As the understanding of HGT's role in tumor evolution and therapy resistance continues to evolve, the synergistic integration of microfluidics and HGT research promises to provide valuable insights into cancer biology, with potential implications for precision oncology and therapeutic strategies.

Evaluation of Expression Level of miR-3135b-5p in Blood Samples of Breast Cancer Patients Experiencing Chemotherapy-Induced Cardiotoxicity.

The efficacy of chemotherapeutics in the treatment of breast cancer is limited by cardiotoxicity, which could lead to irreversible heart failure. The evaluation of miRNA levels as a vital biomarker could predict cardiotoxicity induced by chemotherapy. According to our previous meta-analysis study on patients with heart failure, we found that miR-3135b had a significant increase in patients with heart failure. Therefore, the present study aimed to evaluate the expression level of miR-3135b in the blood sample of patients experiencing chemotherapy-induced cardiotoxicity. Blood samples were collected from breast cancer patients or breast cancer patients who had received chemotherapy and had not experienced any chemotherapy-induced cardiotoxicity (N = 37, control group) and breast cancer patients experiencing chemotherapy-induced cardiotoxicity after chemotherapy (N = 33). The expression level of miR-3135b was evaluated using real-time polymerase chain reaction (RT-PCR). The 2-ΔCt values of miR-3135b were compared between two groups. We observed a significant increase in the expression level of miR-3135b between patients experiencing chemotherapy-induced cardiotoxicity and the control group (P = 0.0001). Besides, the ejection fraction parameter was correlated with the expression level of miR-3135b (r = 0.5 and P = 0.0001). To sum up, miR-3135b might be useful as a promising circulating biomarker in predicting cardiotoxicity induced by chemotherapy. However, more studies are needed to validate miR-3135b as a biomarker for the diagnosis of chemotherapy-induced cardiotoxicity. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01075-3.

Preclinical in vivo assessment of a cell-free multi-layered scaffold prepared by 3D printing and electrospinning for small-diameter blood vessel tissue engineering in a canine model.

Tissue-engineered vascular grafts (TEVGs) are promising alternatives to existing prosthetic grafts. The objective of this study is to evaluate the clinical feasibility of a novel multi-layered small-diameter vascular graft that has a hierarchical structure. Vascular grafts with elaborately designed composition and architecture were prepared by 3D printing and electrospinning and were implanted into the femoral artery of 5 dogs. The patency of the grafts was assessed using Doppler ultrasonography. After 6 months, the grafts were retrieved and histological and SEM examinations were conducted. During implantation, the grafts exhibited resistance to kinking and no blood seepage thanks to the helical structure of the innermost and outermost layers. The grafts showed a high patency rate and remodelling ability. At 6 months post-implantation, the lumen was endothelialized and middle layers were regenerated by infiltration of smooth muscle cells (SMCs) and deposition of extracellular matrix (ECM). These results suggest that the multi-layered vascular graft may be a promising candidate for small-diameter blood vessel tissue engineering in clinical practice.

The molecular perspective on the melanoma and genome engineering of T-cells in targeting therapy.

Melanoma, an aggressive malignant tumor originating from melanocytes in humans, is on the rise globally, with limited non-surgical treatment options available. Recent advances in understanding the molecular and cellular mechanisms underlying immune escape, tumorigenesis, drug resistance, and cancer metastasis have paved the way for innovative therapeutic strategies. Combination therapy targeting multiple pathways simultaneously has been shown to be promising in treating melanoma, eliciting favorable responses in most melanoma patients. CAR T-cells, engineered to overcome the limitations of human leukocyte antigen (HLA)-dependent tumor cell detection associated with T-cell receptors, offer an alternative approach. By genetically modifying apheresis-collected allogeneic or autologous T-cells to express chimeric antigen receptors, CAR T-cells can appreciate antigens on cell surfaces independently of major histocompatibility complex (MHC), providing a significant cancer cell detection advantage. However, identifying the most effective target antigen is the initial step, as it helps mitigate the risk of toxicity due to "on-target, off-tumor" and establishes a targeted therapeutic strategy. Furthermore, evaluating signaling pathways and critical molecules involved in melanoma pathogenesis remains insufficient. This study emphasizes the novel approaches of CAR T-cell immunoediting and presents new insights into the molecular signaling pathways associated with melanoma.

Comparative Analysis and Identification of Spike Mutations in Iranian COVID-19 Samples from the First Three Waves of Disease.

Background: The spike surface glycoprotein of SARS-CoV-2 is the essential protein in virus attachment to the target cell and cell entrance. As this protein contains immunodominant epitopes and is the main target for immune recognition, it is the critical target for vaccine and therapeutics development. In the current research, we analyzed the variability and mutations of the spike glycoprotein isolated from 72 COVID-19-positive patients from Iran's first three waves of disease. Materials and Methods: The RNA was extracted from nasopharyngeal samples of confirmed COVID-19 cases and served as a template for cDNA synthesis and reverse transcriptase polymerase chain reaction. The reverse transcriptase polymerase chain reaction products of each sample were assembled and sequenced. Results: After analysis of 72 sequences, we obtained 46 single nucleotide polymorphisms, including 23 that produce amino acid changes. Our analysis showed that the most frequent mutation was the D614G (in the samples of the second and third waves). Conclusions: Our findings suggest that developing effective vaccines requires identifying the predominant variants of SARS-CoV-2 in each community.

Remdesivir Prescription in Pregnant Women Infected with COVID-19: A Report of Compassionate Use.

Background: Coronavirus disease 2019 (COVID-19) is an infectious disease that the physiological changes in pregnancy can make pregnant patients more susceptible to more severe forms of this infection. Hence, the treatment of COVID-19 in pregnant women can be challenging. This study was designed to evaluate the safety and efficacy of Remdesivir in pregnant women with COVID-19. Materials and Methods: This study was conducted on 150 pregnant women with moderate to severe COVID-19 infection. Remdesivir was prescribed and continued for 5 or 10 days according to the patient's condition. Maternal and pregnancy outcomes and also recovery rates were evaluated. Moreover, additional variables were examined: age, gestational age, symptoms, O2 saturation and laboratory tests at admission, the interval between symptom initiation and admission to hospital and Remdesivir prescription, hospitalization days, and ICU admission. Results: The mean age was 32.37 years. Cough and dyspnea were the most prevalent symptoms (74% and 68.7%, respectively). At the time of admission, 79 (52.7%) women needed low-flow oxygen support, 67 (44.7%) needed high-flow oxygen support, and 4 (2.7%) were intubated. Fifty-four (36%) patients required ICU care. In patients who died (12 women), Remdesivir was prescribed later than those discharged (P value, 0.04). Patients with favorable pregnancy outcomes received Remdesivir earlier than those with unfavorable pregnancy outcomes (P value: 0.008). The recovery rate was 70% (89.9% in the low-flow oxygen, 50.7% in the NIPPV/high flow oxygen, and 0% in the intubated women). Conclusion: The results suggest that the early prescription of Remdesivir in pregnant women with moderate COVID-19 can improve the outcomes.

Effects of the Co-Administration of Morphine and Lipopolysaccharide on Toll-Like Receptor-4/Nuclear Factor Kappa ß Signaling Pathway of MDA-MB-231 Breast Cancer Cells.

Background: The Toll-like receptor 4 (TLR4) gene promotes migration in adenocarcinoma cells. Morphine is an agonist for TLR4 that has a dual role in cancer development. The promoter or inhibitor role of morphine in cancer progression remains controversial. This study aims to evaluate the effects of morphine on the TLR4, myeloid differentiation primary response protein 88-dependent (MyD88), and nuclear factor-kappa B (NF-κB) expressions in the human MDA-MB-231 breast cancer cell line. Materials and Methods: The cells were examined after 24 hours of incubation with morphine using the Boyden chamber system. TLR4, MyD88, and NF-κB mRNA expressions were assessed using quantitative real-time polymerase chain reaction (RT-PCR). The concentration of interleukin-2 beta was also measured using the ELISA assay. Results: According to the findings, three doses of morphine (0.25, 1.25, and 0.025 µM) increased the expression of the TLR4 and NF-κB genes, whereas no significant change was observed in the mRNA expression of MyD88. Furthermore, treatment with morphine and lipopolysaccharide (LPS) significantly decreased the expression of TLR4, MyD88, and NF-κB. However, no significant change was observed in interleukin 2 beta concentration. Conclusions: These findings confirmed the excitatory effects of morphine on TRL4 expression and the MYD88 signaling pathway in vitro.

Steroid in the Treatment of Outpatient COVID-19: A Multicenter Randomized Controlled Trial.

Background: Early treatment of COVID-19 patients could reduce hospitalization and death. The effect of corticosteroids in the outpatient setting is still unknown. This study aimed to determine the effect of corticosteroids in the prevention of hospitalization of nonsevere cases. Materials and Methods: This study is a multicenter randomized controlled trial. Seventy five nonsevere COVID-19 patients presented between days 7 and 14 of their symptoms received either prednisolone or placebo. The primary outcome was hospitalization. The study protocol was registered in the Iranian Registry of Clinical Trials on December 2, 2020 (IRCT20171219037964N2). Results: Although the rate of hospitalization in the prednisolone group was higher than the placebo group (10.8% vs. 7.9%, respectively), it was not statistically significant (P value.,6). One patient in each group reported an adverse event and withdrew the medication. Conclusion: Considering the null effect of corticosteroids in the prevention of hospitalization in outpatient settings, it is suggested not to consider corticosteroids for outpatient treatment.

The Effect of Eight Weeks of Aquatic Exercises on Muscle Strength in Children with Cerebral Palsy: A Case Study.

Background: Cerebral palsy in children is considered a non-progressive brain injury due to abnormal brain development. The aim of this study was to investigate the effect of eight weeks of aquatic exercises on muscle strength in children with cerebral palsy. Materials and Methods: This study was performed on three boys with cerebral palsy with a mean age of 6.5 years. In this research, a single case study method with A1-B-A2 design has been used. After determining the position of the baseline, the intervention began and during 24 sessions of individual intervention, aquatic exercises were presented to the subjects and all three subjects were followed up for 2 consecutive weeks and one month after the end of the intervention. The strength of the flexor muscles of the arms and legs was measured by a power track dynamometer made by JTECK with a threshold of 4.4 N. Results: Based on the indicators of descriptive statistics and visual analysis, the intervention was effective for all three participants in muscle strength, and the strength of individuals after the intervention has improved compared to the baseline stage (percentage). Information overlap for the first and second participant in the strength of right thigh flexors was 75% and for the third participant was 100%. The strength of the upper and lower torso muscles improved after the end of the training compared to the basic stage. Conclusion: Aquatic exercises can increase the strength of children with cerebral palsy and provide a favorable environment for children with cerebral palsy.

Post-COVID-19 Syndrome Mechanisms, Prevention and Management.

As the population of patients recovering from COVID-19 grows, post COVID-19 challenges are recognizing by ongoing evidences at once. Long COVID is defined as a syndrome with a range of persistent symptoms that remain long after (beyond 12 weeks) the acute SARS-CoV-2 infection. Studies have shown that long COVID can cause multi-organ damages with a wide spectrum of manifestations. Many systems, but not limited to, including respiratory, cardiovascular, nervous, gastrointestinal, and musculoskeletal systems, are involved in long COVID. Fatigue and dyspnea are the most common symptoms of long COVID. Long COVID-19 may be driven by tissue damage caused by virus-specific pathophysiologic changes or secondary to pathological long-lasting inflammatory response because of viral persistence, immune dysregulation, and autoimmune reactions. Some risk factors like sex and age, more than five early symptoms, and specific biomarkers have been revealed as a probable long COVID predicator discussed in this review. It seems that vaccination is the only way for prevention of long COVID and it can also help patients who had already long COVID. Managing long COVID survivors recommended being in a multidisciplinary approach, and a framework for identifying those at high risk for post-acute COVID-19 must be proposed. Possible therapeutic options and useful investigation tools for follow-up are suggested in this review. In sum, as evidence and researches are regularly updated, we provide the current understanding of the epidemiology, clinical manifestation, suspected pathophysiology, associated risk factors, and treatment options of long COVID in this review.

A comprehensive review on novel targeted therapy methods and nanotechnology-based gene delivery systems in melanoma.

Melanoma, a malignant form of skin cancer, has been swiftly increasing in recent years. Although there have been significant advancements in clinical treatment underlying a well-understanding of melanoma-susceptible genes and the molecular basis of melanoma pathogenesis, the permanency of response to therapy is frequently constrained by the emergence of acquired resistance and systemic toxicity. Conventional therapies, including surgical resection, chemotherapy, radiotherapy, and immunotherapy, have already been used to treat melanoma and are dependent on the cancer stage. Nevertheless, ineffective side effects and the heterogeneity of tumors pose major obstacles to the therapeutic treatment of malignant melanoma through such strategies. In light of this, advanced therapies including nucleic acid therapies (ncRNA, aptamers), suicide gene therapies, and gene therapy using tumor suppressor genes, have lately gained immense attention in the field of cancer treatment. Furthermore, nanomedicine and targeted therapy based on gene editing tools have been applied to the treatment of melanoma as potential cancer treatment approaches nowadays. Indeed, nanovectors enable delivery of the therapeutic agents into the tumor sites by passive or active targeting, improving therapeutic efficiency and minimizing adverse effects. Accordingly, in this review, we summarized the recent findings related to novel targeted therapy methods as well as nanotechnology-based gene systems in melanoma. We also discussed current issues along with potential directions for future research, paving the way for the next-generation of melanoma treatments.