Role of Non-coding RNAs in the Response of Glioblastoma to Temozolomide.

Chemotherapy and radiotherapy are widely used in clinical practice across the globe as cancer treatments. Intrinsic or acquired chemoresistance poses a significant problem for medical practitioners and researchers, causing tumor recurrence and metastasis. The most dangerous kind of malignant brain tumor is called glioblastoma multiforme (GBM) that often recurs following surgery. The most often used medication for treating GBM is temozolomide chemotherapy; however, most patients eventually become resistant. Researchers are studying preclinical models that accurately reflect human disease and can be used to speed up drug development to overcome chemoresistance in GBM. Non-coding RNAs (ncRNAs) have been shown to be substantial in regulating tumor development and facilitating treatment resistance in several cancers, such as GBM. In this work, we mentioned the mechanisms of how different ncRNAs (microRNAs, long non-coding RNAs, circular RNAs) can regulate temozolomide chemosensitivity in GBM. We also address the role of these ncRNAs encapsulated inside secreted exosomes.

The First Case of Eruptive Pyogenic Granuloma following COVID-19 Vaccination.

Introduction: Pyogenic granuloma presents clinically as a rapidly growing, friable, red papule of skin or mucosa, commonly measuring less than 10 mm with frequent bleeding due to ulceration. Angioproliferative diseases including pyogenic granuloma and cherry angioma have been reported during COVID-19 infection or following COVID-19 vaccination. Case Presentation: Here, we report a 52-year-old female patient who developed diffuse skin eruptions 3 weeks after the second dose of COVID-19 vaccination. Conclusion: As per our knowledge, this is the first case of eruptive PG following COVID-19 vaccination. Oral propranolol and PDL laser therapy were administered after obtaining inconvenient results from electro-cautery, and there was a good response within 6 weeks of starting therapy, defined by the cessation of new lesion formation and a decrease in the size of large lesions.

Key barriers to the provision and utilization of maternal health services in low-and lower-middle-income countries; a scoping review.

BACKGROUND: The preservation and promotion of maternal health (MH) emerge as vital global health objectives. Despite the considerable emphasis on MH, there are still serious challenges to equitable access to MH services in many countries. This review aimed to determine key barriers to the provision and utilization of MH services in low- and lower-middle-income countries (LLMICs). METHODS: In this scoping review, we comprehensively searched four online databases from January 2000 to September 2022. In this study, the approach proposed by Arksey and O'Malley was used to perform the review. Consequently, 117 studies were selected for final analysis. To determine eligibility, three criteria of scoping reviews (population, concept, and context) were assessed alongside the fulfillment of the STROBE and CASP checklist criteria. To synthesize and analyze the extracted data we used the qualitative content analysis method. RESULTS: The main challenges in the utilization of MH services in LLMICs are explained under four main themes including, knowledge barriers, barriers related to beliefs, attitudes and preferences, access barriers, and barriers related to family structure and power. Furthermore, the main barriers to the provision of MH services in these countries have been categorized into three main themes including, resource, equipment, and capital constraints, human resource barriers, and process defects in the provision of services. CONCLUSIONS: The evidence from this study suggests that many of the barriers to the provision and utilization of MH services in LLMICs are interrelated. Therefore, in the first step, it is necessary to prioritize these factors by determining their relative importance according to the specific conditions of each country. Consequently, comprehensive policies should be developed using system modeling approaches.

Advancements in tissue engineering for cardiovascular health: a biomedical engineering perspective.

Myocardial infarction (MI) stands as a prominent contributor to global cardiovascular disease (CVD) mortality rates. Acute MI (AMI) can result in the loss of a large number of cardiomyocytes (CMs), which the adult heart struggles to replenish due to its limited regenerative capacity. Consequently, this deficit in CMs often precipitates severe complications such as heart failure (HF), with whole heart transplantation remaining the sole definitive treatment option, albeit constrained by inherent limitations. In response to these challenges, the integration of bio-functional materials within cardiac tissue engineering has emerged as a groundbreaking approach with significant potential for cardiac tissue replacement. Bioengineering strategies entail fortifying or substituting biological tissues through the orchestrated interplay of cells, engineering methodologies, and innovative materials. Biomaterial scaffolds, crucial in this paradigm, provide the essential microenvironment conducive to the assembly of functional cardiac tissue by encapsulating contracting cells. Indeed, the field of cardiac tissue engineering has witnessed remarkable strides, largely owing to the application of biomaterial scaffolds. However, inherent complexities persist, necessitating further exploration and innovation. This review delves into the pivotal role of biomaterial scaffolds in cardiac tissue engineering, shedding light on their utilization, challenges encountered, and promising avenues for future advancement. By critically examining the current landscape, we aim to catalyze progress toward more effective solutions for cardiac tissue regeneration and ultimately, improved outcomes for patients grappling with cardiovascular ailments.

Family-based association of HLA-DRB1 and DQB1 alleles and haplotypes in a group of Iranian Type 1 diabetes children.

This family-based study was conducted in a group of Iranians with Type 1 diabetes (T1D) to investigate the transmission from parents of risk and non-risk HLA alleles and haplotypes, and to estimate the genetic risk score for this disease within this population. A total of 240 T1D subjects including 111 parent-child trios (111 children with T1D, 133 siblings, and 222 parents) and 330 ethnically matched healthy individuals were recruited. High-resolution HLA typing for DRB1/DQB1 loci was performed for all study subjects (n = 925) using polymerase chain reaction-sequence-specific oligonucleotide probe method. The highest predisposing effect on developing T1D was conferred by the following haplotypes both in all subjects and in probands compared to controls: DRB1*04:05-DQB1*03:02 (Pc = 2.97e-06 and Pc = 6.04e-10, respectively), DRB1*04:02-DQB1*03:02 (Pc = 5.94e-17 and Pc = 3.86e-09, respectively), and DRB1*03:01-DQB1*02:01 (Pc = 8.26e-29 and Pc = 6.56e-16, respectively). Conversely, the major protective haplotypes included DRB1*13:01-DQB1*06:03 (Pc = 6.99e-08), DRB1*15:01-DQB1*06:02 (Pc = 2.97e-06) in the cases versus controls. Also, DRB1*03:01-DQB1*02:01/DRB1*04:02|05-DQB1*03:02 and DRB1*03:01-DQB1*02:01/DRB1*03:01-DQB1*02:01 diplotypes conferred the highest predisposing effect in the cases (Pc = 8.65e-17 and Pc = 6.26e-08, respectively) and in probands (Pc = 5.4e-15 and Pc = 0.001, respectively) compared to controls. Transmission disequilibrium test showed that the highest risk was conferred by DRB1*04:02-DQB1*03:02 (Pc = 3.26e-05) and DRB1*03:01-DQB1*02:01 (Pc = 1.78e-12) haplotypes and the highest protection by DRB1*14:01-DQB1*05:03 (Pc = 8.66e-05), DRB1*15:01-DQB1*06:02 (Pc = 0.002), and DRB1*11:01-DQB1*03:01 (Pc = 0.0003) haplotypes. Based on logistic regression analysis, carriage of risk haplotypes increased the risk of T1D development 24.5 times in the Iranian population (p = 5.61e-13). Also, receiver operating characteristic curve analysis revealed a high predictive power of those risk haplotypes in discrimination of susceptible from healthy individuals (area under curve: 0.88, p = 5.5e-32). Our study highlights the potential utility of genetic risk assessment based on HLA diplotypes for predicting T1D risk in individuals, particularly among family members of affected children in our population.

Determination of HLA class II risk alleles and prediction of self/non-self-epitopes contributing Hashimoto's thyroiditis in a group of Iranian patients.

One of the probable hypotheses for the onset of autoimmunity is molecular mimicry. This study aimed to determine the HLA-II risk alleles for developing Hashimoto's thyroiditis (HT) in order to analyze the molecular homology between candidate pathogen-derived epitopes and potentially self-antigens (thyroid peroxidase, TPO) based on the presence of HLA risk alleles. HLA-DRB1/-DQB1 genotyping was performed in 100 HT patients and 330 ethnically matched healthy controls to determine the predisposing/protective alleles for HT disease. Then, in silico analysis was conducted to examine the sequence homology between epitopes derived from autoantigens and four potentially relevant pathogens and their binding capacities to HLA risk alleles based on peptide docking analysis. We identified HLA-DRB1*03:01, *04:02, *04:05, and *11:04 as predisposing alleles and DRB1*13:01 as a potentially predictive allele for HT disease. Also, DRB1*11:04 ~ DQB1*03:01 (Pc = 0.002; OR, 3.97) and DRB1*03:01 ~ DQB1*02:01 (Pc = 0.004; OR, 2.24) haplotypes conferred a predisposing role for HT. Based on logistic regression analysis, carrying risk alleles increased the risk of HT development 4.5 times in our population (P = 7.09E-10). Also, ROC curve analysis revealed a high predictive power of those risk alleles for discrimination of the susceptible from healthy individuals (AUC, 0.70; P = 6.6E-10). Analysis of peptide sequence homology between epitopes of TPO and epitopes derived from four candidate microorganisms revealed a homology between envelop glycoprotein D of herpes virus and sequence 151-199 of TPO with remarkable binding capacity to HLA-DRB1*03:01 allele. Our findings indicate the increased risk of developing HT in those individuals carrying HLA risk alleles which can also be related to herpes virus infection.

A computational approach to design a multiepitope vaccine against H5N1 virus.

Since 1997, highly pathogenic avian influenza viruses, such as H5N1, have been recognized as a possible pandemic hazard to men and the poultry business. The rapid rate of mutation of H5N1 viruses makes the whole process of designing vaccines extremely challenging. Here, we used an in silico approach to design a multi-epitope vaccine against H5N1 influenza A virus using hemagglutinin (HA) and neuraminidase (NA) antigens. B-cell epitopes, Cytotoxic T lymphocyte (CTL) and Helper T lymphocyte (HTL) were predicted via IEDB, NetMHC-4 and NetMHCII-2.3 respectively. Two adjuvants consisting of Human ß-defensin-3 (HßD-3) along with pan HLA DR-binding epitope (PADRE) have been chosen to induce more immune response. Linkers including KK, AAY, HEYGAEALERAG, GPGPGPG and double EAAAK were utilized to link epitopes and adjuvants. This construct encodes a protein having 350 amino acids and 38.46 kDa molecular weight. Antigenicity of ~ 1, the allergenicity of non-allergen, toxicity of negative and solubility of appropriate were confirmed through Vaxigen, AllerTOP, ToxDL and DeepSoluE, respectively. The 3D structure of H5N1 was refined and validated with a Z-Score of - 0.87 and an overall Ramachandran of 99.7%. Docking analysis showed H5N1 could interact with TLR7 (docking score of - 374.08 and by 4 hydrogen bonds) and TLR8 (docking score of - 414.39 and by 3 hydrogen bonds). Molecular dynamics simulations results showed RMSD and RMSF of 0.25 nm and 0.2 for H5N1-TLR7 as well as RMSD and RMSF of 0.45 nm and 0.4 for H5N1-TLR8 complexes, respectively. Molecular Mechanics Poisson-Boltzmann Surface Area (MM/PBSA) confirmed stability and continuity of interaction between H5N1-TLR7 with the total binding energy of - 29.97 kJ/mol and H5N1-TLR8 with the total binding energy of - 23.9 kJ/mol. Investigating immune response simulation predicted evidence of the ability to stimulate T and B cells of the immunity system that shows the merits of this H5N1 vaccine proposed candidate for clinical trials.

Molecular mechanism of lncRNAs in pathogenesis and diagnosis of auto-immune diseases, with a special focus on lncRNA-based therapeutic approaches.

Autoimmune diseases are a diverse set of conditions defined by organ damage due to abnormal innate and acquired immune system responses. The pathophysiology of autoimmune disorders is exceedingly intricate and has yet to be fully understood. The study of long non-coding RNAs (lncRNAs), non-protein-coding RNAs with at least 200 nucleotides in length, has gained significant attention due to the completion of the human genome project and the advancement of high-throughput genomic approaches. Recent research has demonstrated how lncRNA alters disease development to different degrees. Although lncRNA research has made significant progress in cancer and generative disorders, autoimmune illnesses are a relatively new research area. Moreover, lncRNAs play crucial functions in differentiating various immune cells, and their potential relationships with autoimmune diseases have received growing attention. Because of the importance of Th17/Treg axis in auto-immune disease development, in this review, we discuss various molecular mechanisms by which lncRNAs regulate the differentiation of Th17/Treg cells. Also, we reviewed recent findings regarding the several approaches in the application of lncRNAs in the diagnosis and treatment of human autoimmune diseases, as well as current challenges in lncRNA-based therapeutic approaches to auto-immune diseases.

Doxorubicin-loaded zymosan nanoparticles: Synergistic cytotoxicity and modulation of apoptosis and Wnt/ß-catenin signaling pathway in C26 colorectal cancer cells.

Zymosan is a ß-glucan isolated from Saccharomyces cerevisiae that could be employed for drug delivery. We synthesized zymosan nanoparticles and measured their structural and morphological properties using XRD, UV-Vis spectroscopy, TEM and AFM. The loading of doxorubicin (DOX) onto the nanoparticles was confirmed by FT-IR, and the DOX release was shown to be pH-dependent. The effect of these agents on C26 cell viability was evaluated by MTT tests and the expression of genes connected with the Wnt/ß-catenin pathway and apoptosis were analyzed by RT-qPCR and Western blotting. Treatments were able to suppress the proliferation of C26 cells, and the zymosan nanocarriers loaded with DOX enhanced the anti-proliferative effect of DOX in a synergistic manner. Zymosan nanoparticles were able to suppress the expression of cyclin D1, VEGF, ZEB1, and Twist mRNAs. Treatment groups upregulated the expression of caspase-8, while reducing the Bax/Bcl-2 ratio, thus promoting apoptosis. In conclusion, zymosan nanoparticles as DOX nanocarriers could provide a more targeted drug delivery through pH-responsiveness, and showed synergistic cytotoxicity by modifying Wnt/ß-catenin signaling and apoptosis.

Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case-control studies.

Background: The advanced glycation end product (AGE) is produced from the nonenzymatic reaction between glucose and macromolecules by aging. Accumulation of AGE causes functional and structural changes in body proteins that lead to impairment of tissue protein functions. We aimed to validate AGE measurement by skin autofluorescence (SAF) in diabetes mellitus (DM) compared to the nondiabetes population. Materials and Methods: We searched the PubMed, Cochrane, and Scopus databases from their inception till September 18, 2022, for casecontrol studies measuring AGE by SAF. Nonhuman studies, as well as review articles, study proposals, editorials, case reports, or congress posters, were excluded. We used a random effects model to assess the standard mean difference (MD) of age, body mass index (BMI), HbA1c, and SAF between diabetes and nondiabetes individuals. Results: Higher SAF in DM patients indicated more accumulation of AGE compared with the nondiabetic population. Furthermore, HbA1c was considerably higher in DM patients. The MD of age, male gender, and BMI were significantly different between the DM individuals, compared with nondiabetic subjects, which can lead to altered SAF level and AGE production. There was a remarkable heterogeneity between diabetes and nondiabetes when measuring age, gender, and BMI, as well as HbA1c and SAF level. Conclusion: This study could not confirm the validity of SAF as a surrogate marker in diabetes patients. Interestingly, metabolic load and high BMI can increase SAF, considerably. Altogether, SAF could be helpful in the future as a marker for metabolic syndrome or diabetes.

Combined training in addition to cortisol reduction can improve the mental health of girls with precocious puberty and obesity.

Background: Obesity and central precocious puberty (CPP) are associated with increased anxiety, depression, and anger in girls. The contribution of exercise as an efficacious component in decreasing anxiety, depression, and anger has been increasingly recognized. Objectives: This study aims to evaluate the effects of combined training on cortisol, anxiety, depression, and anger in overweight and obese girls with CPP. Methods: The study involved 30 girls aged 7-9 years diagnosed with CPP (undergoing triptorelin treatment) and dealing with obesity. In addition, these girls scored higher than the cut-off line for anxiety, depression, and anger. The participants were divided into two groups, with 15 individuals in each group. The exercise group engaged in 60 min of combined aerobic and resistance training three times per week for a duration of 12 weeks. On the other hand, the control group did not receive any training. Throughout the study, the serum cortisol levels were measured in both groups. Anxiety, anger, and depression questionnaires were also completed at three different stages, namely, baseline, 12 weeks, and 16 weeks (after a 4-week period of detraining). Results: In the exercise group, there was a significant decrease (P < 0.05) in cortisol serum levels and anxiety, depression, and anger scores. These changes were observed consistently during detraining (P > 0.05). However, in the control group, only the depression score significantly decreased (P < 0.05). Conclusions: Based on the results, it can be concluded that combined training is a method to improve the mental health of CPP girls. Clinical Trial Registration: https://en.irct.ir/trial/61990, identifier IRCT20170411033378N10.

Two cases of neglected leishmaniasis with marked facial disfigurement: A diagnostic conundrum.

Key Clinical Message: There is a need to pay more attention to cutaneous leishmaniasis in endemic regions which may mimic other dermatoses and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy. Abstract: Leishmaniasis is a vector-borne disease with a variety of Clinical manifestations. Cutaneous leishmaniasis (CL) is the most common form of disease and can mimic other dermatoses. We describe two unusual cases of chronic leishmaniasis that remained undiagnosed for many years and led to superimposition of squamous cell carcinoma (SCC) on lesions of one patient. These reports showed that the leishmaniasis should be borne in mind by clinicians when encountering any infiltrated lesion in patients from endemic regions and treatment should be initiated with a strong clinical suspicion even without any histopathologic or PCR confirmation to avoid disfigurement or development of secondary malignancy.

Molecular landscape of LncRNAs in bladder cancer: From drug resistance to novel LncRNA-based therapeutic strategies.

Bladder cancer (BC) is a common and serious type of cancer that ranks among the top ten most prevalent malignancies worldwide. Due to the high occurrence rate of BC, the aggressive nature of cancer cells, and their resistance to medication, managing this disease has become a growing challenge in clinical care. Long noncoding RNAs (lncRNAs) are a group of RNA transcripts that do not code for proteins and are more than 200 nucleotides in length. They play a significant role in controlling cellular pathways and molecular interactions during the onset, development and progression of different types of cancers. Recent advancements in high-throughput gene sequencing technology have led to the identification of various differentially expressed lncRNAs in BC, which indicate abnormal expression. In this review, we summarize that these lncRNAs have been found to impact several functions related to the development of BC, including proliferation, cell growth, migration, metastasis, apoptosis, epithelial-mesenchymal transition, and chemo- and radio-resistance. Additionally, lncRNAs may improve prognosis prediction for BC patients, indicating a future use for them as prognostic and diagnostic biomarkers for BC patients. This review highlights that genetic tools and anti-tumor agents, such as CRISPR/Cas systems, siRNA, shRNA, antisense oligonucleotides, and vectors, have been created for use in preclinical cancer models. This has led to a growing interest in using lncRNAs based on positive research findings.

Mesenchymal stem cell therapy for non-healing diabetic foot ulcer infection: New insight.

Diabetic foot ulcer (DFU) is considered the most catastrophic complication of diabetes mellitus (DM), leading to repeated hospitalizations, infection, gangrene, and finally amputation of the limb. In patients suffering from diabetes mellitus, the wound-healing process is impaired due to various factors such as endothelial dysfunction and synthesis of advanced glycation end-products, hence, conventional therapeutic interventions might not be effective. With increasing therapeutic applications of mesenchymal stem cells (MSCs) in recent years, their potential as a method for improving the wound-healing process has gained remarkable attention. In this field, mesenchymal stem cells exert their beneficial effects through immunomodulation, differentiation into the essential cells at the site of ulcers, and promoting angiogenesis, among others. In this article, we review cellular and molecular pathways through which mesenchymal stem cell therapy reinforces the healing process in non-healing Diabetic foot ulcers.

Reduction of CO2 emission through a photocatalytic process using powder and coated zeolite-supported TiO2 under concentrated sunlight irradiation.

The efficiency of a novel synthetic zeolite (Ze) prepared from stone cutting sludge and a natural zeolite (clinoptilolite, Cp) as the support of TiO2 photocatalyst was examined for the CO2 removal under solar irradiation using a designed parabolic trough collector (PTC). The used samples were characterized using XRF, BET, SEM/EDS, and XPS analyses. The enhanced sunlight irradiation obtained by PTC increased the performance of CO2 photocatalytic removal. The maximum CO2 adsorption by TiO2-Ze and TiO2-Cp composites was 21.1% and 28.4% which increased to 61.8% and 78.9% under sunlight irradiation, respectively. The efficiency of zeolite-TiO2 composites for CO2 removal was approximately two times higher than zeolites and TiO2 alone. The performance of TiO2-Ze-coated composite with lower use of photocatalyst for CO2 adsorption and photocatalytic removal was better than that of powder one. Regeneration of TiO2-Ze using NaOH solution improved its removal efficiency. The adsorption behavior of CO2 on TiO2-Ze composite was well described by the Langmuir isotherm and the pseudo-first-order kinetic model. This work promises CO2 reduction using natural and synthetic zeolite as an efficient photocatalyst support under solar irradiation.

COVID-19 vaccines and filler reactions: Should it be considered as a concern?

BACKGROUND: Any implant or external material used in the body tissues can potentially be followed by autoimmune or inflammatory reactions. With the global vaccination program against COVID-19, the reports of tissue filler reactions would be increasingly demonstrated. AIM: To summarize the data regarding COVID vaccination and filler reactions. METHOD: We reviewed the existing data in this regard through searching on PubMed, Google Scholar and Scopus. All of the relevant papers published until March 2022, which we could access to their fulltexts were included. RESULTS: Here, we summarized the data regarding COVID-19 vaccination and filler reactions and discussed its etiopathogenesis, management, and importance. CONCLUSION: Although the end of pandemic was announced, the necessity of continuing COVI-D19 vaccination in future mandates gathering data regarding safety of vaccines.

COVID vaccine recommendations in dermatologic patients on immunosuppressive agents: Lessons learned from pandemic.

BACKGROUND: Since SARS-CoV2 vaccines were approved without enough long-term monitoring due to emergent situations, some issues have been raised about timing and protocol of receiving them by patients treated by different immunosuppressive agents. AIM AND METHOD: Here, we present different aspects of SARS-CoV-2 vaccination in such patients in the field of dermatology. RESULT: In brief, SARS-CoV-2 vaccination is recommended in all dermatologic patients, regardless of their disorders and therapeutic regimens. Nevertheless, special considerations should be given to the immunosuppressive therapy and its association with vaccination timing due to the decreased immunogenicity of vaccines in this setting. CONCLUSION: Novel biologic immunotherapies are advantageous over conventional systemic therapies not only in their safety and selective functions but also in this aspect that many of them do not affect vaccines immunogenicity.

The COVID-19 pandemic and its impact on esthetic dermatology.

In general, the world population interest has increased for maintaining youthfulness and having better appearance since this leads to a better mental wellbeing and self-estimate. The coronavirus disease 2019 (COVID-19) pandemic has revolutionized every field of medicine. As every specialty has been affected by limitations caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), this branch of medicine has also needed certain precautions for safer practice in the COVID era. With the global vaccination program against COVID-19, reports of some cutaneous reactions in patients have been undergone various esthetic procedures including filler or botox injection would be increasingly demonstrated. Although the end of pandemic was announced, the necessity of continuing COVID vaccination in future mandates gathering data regarding safety of vaccines. Herein, we presented a comprehensive review on various aspects of association between esthetic medicine or cosmetic dermatology and COVID-19.

A Young Boy with Brittle Hair.

Trichothiodystrophy (TTD) is a rare multisystem disorder with an autosomal recessive mode of inheritance. TTD presentations vary from only hair abnormalities like brittle, fragile hair to physical and mental retardation. Mutations of DNA repair genes have been identified as responsible for the disease. A 5-year-old boy presented with sparse, short, and brittle hair to our clinic. He was born to consanguineous parents. Trichoscopy and light microscopy revealed broken hairs with no specific shaft defect. Due to the inaccessibility of the polarized microscopy, a bedside technique was employed. We used a polarized dermatoscope and a mirror in order of achieving transillumination of the hair shafts, which revealed striking bright and dark bands. These bands are referred to as "tiger tail," which is the pathognomonic sign of TTD. Subsequent polarizing microscopy also confirmed the clinical diagnosis. This highlighted a feasible method for observing the tiger tail, which expanded the known clinical diagnostic tools of TTD.