Non-coding RNAs as Key Regulators of the Notch Signaling Pathway in Glioblastoma: Diagnostic, Prognostic, and Therapeutic Targets.

Glioblastoma multiforme (GBM) is a highly invasive brain malignancy originating from astrocytes, accounting for approximately 30% of central nervous system malignancies. Despite advancements in therapeutic strategies including surgery, chemotherapy, and radiopharmaceutical drugs, the prognosis for GBM patients remains dismal. The aggressive nature of GBM necessitates the identification of molecular targets and the exploration of effective treatments to inhibit its proliferation. The Notch signaling pathway, which plays a critical role in cellular homeostasis, becomes deregulated in GBM, leading to increased expression of pathway target genes such as MYC, Hes1, and Hey1, thereby promoting cellular proliferation and differentiation. Recent research has highlighted the regulatory role of non-coding RNAs (ncRNAs) in modulating Notch signaling by targeting critical mRNA expression at the post-transcriptional or transcriptional levels. Specifically, various types of ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been shown to control multiple target genes and significantly contribute to the carcinogenesis of GBM. Furthermore, these ncRNAs hold promise as prognostic and predictive markers for GBM. This review aims to summarize the latest studies investigating the regulatory effects of ncRNAs on the Notch signaling pathway in GBM.

Gene Therapy for Neuropsychiatric Disorders: Potential Targets and Tools.

Neuropsychiatric disorders that affect the central nervous system cause considerable pressures on the health care system and have a substantial economic burden on modern societies. The present treatments based on available drugs are mostly ineffective and often costly. The molecular process of neuropsychiatric disorders is closely connected to modifying the genetic structures inherited or caused by damage, toxic chemicals, and some current diseases. Gene therapy is presently an experimental concept for neurological disorders. Clinical applications endeavor to alleviate the symptoms, reduce disease progression, and repair defective genes. Implementing gene therapy in inherited and acquired neurological illnesses entails the integration of several scientific disciplines, including virology, neurology, neurosurgery, molecular genetics, and immunology. Genetic manipulation has the power to minimize or cure illness by inducing genetic alterations at endogenous loci. Gene therapy that involves treating the disease by deleting, silencing, or editing defective genes and delivering genetic material to produce therapeutic molecules has excellent potential as a novel approach for treating neuropsychiatric disorders. With the recent advances in gene selection and vector design quality in targeted treatments, gene therapy could be an effective approach. This review article will investigate and report the newest and the most critical molecules and factors in neuropsychiatric disorder gene therapy. Different genome editing techniques available will be evaluated, and the review will highlight preclinical research of genome editing for neuropsychiatric disorders while also evaluating current limitations and potential strategies to overcome genome editing advancements.

Frequency Distribution of Cutaneous Leishmaniasis in the Central Region of Iran

Objective: Cutaneous leishmaniasis is a zoonotic disease and one of the most widespread diseases in our country. This illness is a significant public health concern in most Iranian provinces. Therefore, it is necessary to study the prevalence and identification of new sources of this problem in many regions of Iran. The present study was intended to investigate the epidemiology of cutaneous leishmaniasis in Yazd city. Methods: This descriptive-analytical and cross-sectional study was performed on 121 patients with leishmaniasis in Nicopoor Center, Yazd in 2017. According to ethical and research standards, information about patients, including their gender, age, occupation, location and number of lesions and month of illness were collected and evaluated using SPSS Statistics, Version 21. Results: The highest incidence of leishmaniasis occurred in adults over 50 years of age (28.9%) and in children under the age of 10 (23.1%). An incidence of 41.3% was observed for other occupations, including driver, farmer and child. In second place, the highest frequency was related to housewives (25.6%), and in third place, a higher frequency was observed in students (19%). The most common venereal sites were the hands (38.8%), in second place the feet (28.1%) and in third place the face (15.7%). The highest seasonal frequency of leishmaniasis occurred during the autumn. Conclusion: In light of the current study findings and the adverse effects of leishmaniasis, it is necessary to design strategies with the aim of controlling the disease and to implement appropriate actions with the intention of decreasing its prevalence nationally.

Treatment outcomes and influencing factors on patients with pulmonary tuberculosis: a retrospective study

Introduction: Tuberculosis infection caused by Mycobacterium tuberculosis is one of the most common infectious diseases, especially in countries such as Iran. The course of treatment and the number of drugs used vary depending on the severity of the disease and the parts of the body involved. The resistant tuberculosis to treatment has increased in recent years. Thus, this study was conducted to investigate the frequency distribution of response to treatment of patients with tuberculosis in Sirjan, Iran. Methods: This descriptive cross-sectional study investigated all patients with tuberculosis in Sirjan city who had referred to health centers during the years 2011-2019. The data collection tool was a pre-prepared checklist that included information on age, sex, sputum smear results, sputum culture results, diabetes, patients' nationality, drug side effects, and response to treatment. Finally, data was entered into SPSS version 22, and analyzed. Results: In this study, the overall response rate was 83% and the mortality rate was 10%. Between the frequency distribution of response to treatment in terms of gender, age, sputum smear results, sputum culture results, patients' nationality and diabetes was not statistically significant difference. Also, no statistically significant difference was found between the frequency distribution of pulmonary TB treatment response in terms of drug allergy, drug hepatitis and other drug side effects. Conclusion: According to results, can be concluded that none of the variables: age, sex, smear and culture result, and history of diabetes have no an effect on response to treatment and mortality of tuberculosis (AU)

An overview of vaccine development for COVID-19.

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.

Nrf2 Regulation by Curcumin: Molecular Aspects for Therapeutic Prospects.

Nuclear factor erythroid 2 p45-related factor (2Nrf2) is an essential leucine zipper protein (bZIP) that is primarily located in the cytoplasm under physiological conditions. Nrf2 principally modulates endogenous defense in response to oxidative stress in the brain.In this regard, Nrf2 translocates into the nucleus and heterodimerizes with the tiny Maf or Jun proteins. It then attaches to certain DNA locations in the nucleus, such as electrophile response elements (EpRE) or antioxidant response elements (ARE), to start the transcription of cytoprotective genes. Many neoplasms have been shown to have over activated Nrf2, strongly suggesting that it is responsible for tumors with a poor prognosis. Exactly like curcumin, Zinc-curcumin Zn (II)-curc compound has been shown to induce Nrf2 activation. In the cancer cell lines analyzed, Zinc-curcumin Zn (II)-curc compound can also display anticancer effects via diverse molecular mechanisms, including markedly increasing heme oxygenase-1 (HO-1) p62/SQSTM1 and the Nrf2 protein levels along with its targets. It also strikingly decreases the levels of Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1) protein.As a result, the crosstalk between p62/SQSTM1 and Nrf2 could be used to improve cancer patient response to treatments. The interconnected anti-inflammatory and antioxidative properties of curcumin resulted from its modulatory effects on Nrf2 signaling pathway have been shown to improve insulin resistance. Curcumin exerts its anti-inflammatory impact through suppressing metabolic reactions and proteins such as Keap1 that provoke inflammation and oxidation. A rational amount of curcumin-activated antioxidant Nrf2 HO-1 and Nrf2-Keap1 pathways and upregulated the modifier subunit of glutamate-cysteine ligase involved in the production of the intracellular antioxidant glutathione. Enhanced expression of glutamate-cysteine ligase, a modifier subunit (GLCM), inhibited transcription of glutamate-cysteine ligase, a catalytic subunit (GCLC). A variety of in vivo, in vitro and clinical studies has been done so far to confirm the protective role of curcumin via Nrf2 regulation. This manuscript is designed to provide a comprehensive review on the molecular aspects of curcumin and its derivatives/analogs via regulation of Nrf2 regulation.

Effect of Lidocaine 2% on Bacterial Culture of Bronchial Fluid.

OBJECTIVE: To evaluate the action of 2% lidocaine on the culture results of bronchial fluid in patients suspected of having lower respiratory tract infections. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Shahid Sadoughi Hospital, Yazd, Iran, from November 2014 to November 2015. METHODOLOGY: Patients suspected of lower respiratory tract infections referred to bronchoscopy unit of the Hospital were included. Those with incomplete questionnaire and bronchoscopy contraindication were excluded. Bronchial fluid was aspirated before and after local application of 2% lidocaine and cultured, according to the suspected clinical diagnosis. Finally, statistical analysis was performed using SPSS software, version 17.0. For statistical comparisons, McNemar's test was used. Level of significance was kept at p <0.05. RESULTS: The mean age of the study population was 51.83 ±15.93 with a range of 25 - 80 years. Out of 130 patients, 60 patients had positive culture results. Nineteen (31.7%) cases had positive culture for tuberculosis and 41 (63.3%) cases had positive results for other bacteria before intervention that did not change after using 2% lidocaine (p=1). In 70 (53.84%) cases, results were negative before and after use of 2% lidocaine. CONCLUSION: No significant difference was found between culture results before and after the use of lidocaine. Therefore, lidocaine can be used during bronchoscopy to increase patient tolerance.

Leishmaniasis of the Feet Sole: A Case Report.

Here we report the case of a patient with cutaneous leishmaniasis, who was referred to our clinic in Yazd, Iran. On examining the patient, who was a housekeeper, we found a small plaque in the palmoplantar region due to cutaneous leishmaniasis. She had not any history from an identical case in this patient. After treatment, the lesions improved.

The Prevalence of Occult Hepatitis B Virus in the Hemodialysis Patients in Yazd, Iran.

Occult HBV infection of hemodialysis (HD) patients is informative in terms of virus transmission. It may be of clinical importance in HD patients. The aim of this study was to investigate the prevalence of anti-HBc in the HD Patients. Number of 126 patients undergoing hemodialysis were included in this study from main hemodialysis units in Yazd. Hepatitis B surface antigens (HBsAg), hepatitis B core antibody (anti-HBc) were examined in all subjects. Finally, stored serum samples from anti-HBcAb positive, HBsAg negative patients were anonymised and tested for HBV DNA by real time quantitative PCR assay. The age range of the patients was 17-88 years. Of the 126 patients, 123 patients (97.6%) were HBC-Ab negative and 3 (2.4%) were positive. Of 3 patients with Anti-HBC positive, HBV DNA was detected in 1 patient. This study showed a low rate of isolated anti-HBc (2.4%). HBV DNA was also detected in 1 patient.

Comparison of samples obtained from bronchoscopy of patients with and without bronchial anthracosis for investigating the prevalence of Mycobacterium tuberculosis.

OBJECTIVE: Bronchial anthracosis is caused by the deposition of carbon, silica or asbestos particles in mucosal and submucosal cells and macrophages, and it can lead to chronic bronchial obstruction. Certain studies have reported an association between bronchial anthracosis and infection with Mycobacterium tuberculosis. This study aimed to compare the samples obtained from bronchoscopy of patients with and without bronchial anthracosis for investigating the prevalence of Mycobacterium tuberculosis. METHODS: This was a cross-sectional study conducted between 2010 and 2013. A total of 514 patients underwent diagnostic bronchoscopy for pulmonary diseases. A sample of bronchoalveolar lavage fluid was taken from each patient and tested for Mycobacterium tuberculosis through smear and culture techniques. The data were analyzed with Chi-square and Fisher's exact test, with p ≤.05 set as the significant level. RESULTS: Totally, 514 patients were evaluated through bronchoscopy; bronchial anthracosis was diagnosed in 207 cases, of which 129 (62.3%) were women. The rate of pulmonary tuberculosis was significantly higher (p = .002) in the bronchial anthracosis group. CONCLUSION: In our study, the prevalence of pulmonary tuberculosis was significantly higher in the bronchial anthracosis group. Given that pulmonary tuberculosis is still one of the health problems of the present century, increased attention to specific risk factors including bronchial anthracosis in patients having pulmonary symptoms is recommended.

Skin Rashes on Leg in Brucellosis: a Rare Presentation.

Brucellosis is the most widespread zoonotic infection in the world. The disease is endemic in countries bordering the Mediterranean Sea. It is an important re-emerging infectious disease. This disease is closely associated with the evolution of mankind as an agrarian society linked to the practice of shepherding and popularization of animal husbandry. The patients with this disease are typically present with chills, fever, asthenia and sweating. This paper describes a patient with brucellosis and skin rashes on the leg. A 41-year-old man presented with fever, ataxia, and dysarthria. He was a shepherd. The patient reported the loss of appetite, arthralgia and weight loss during previous five months. Finally, he was diagnosed with brucellosis by positive blood culture and high titer for Brucella agglutination test. The clinical manifestation of brucellosis is very broad, ranging from asymptomatic infection to serious debilitating disease. Current patient had skin rashes on his leg. Brucellosis must be considered in the differential diagnosis of acute infections, especially if there is a history of fresh milk product ingestion and living in an endemic region.

Report of nine cases of Crimean-Congo haemorrhagic fever From Iran.

Crimean-Congo haemorrhagic fever (CCHF) is an often fatal viral infection described in about 30 countries around the world. It is transmitted to humans by the bite of an infected tick and by direct contact with blood or tissue from infected humans and livestock. In the following, we report nine cases of CCHF disease. This paper reported nine human CCHF cases, two in Tabas and Bandar Abbas and seven in Yazd. They were 21-, 33-, 28-, 29-, 61, 34, 35, 36 and 52 year-old men. The first, second and third patients were butchers and other patients were farmers. CCHF should be investigated in the patients with fever, bleeding and low platelet counts.

Compliance with hepatitis B vaccination among adult males with sexually transmitted infections.

BACKGROUND: Sexually transmitted infections (STIs) are a diverse group of infections caused by widely differing microorganisms (viruses, protozoa, bacteria, yeasts, ectoparasites and even a nematode), with transmission from person to person by sexual contact as its common characteristic. In all societies, sexually transmitted infections rank among the most common infectious diseases. These patients are at risk for hepatitis B virus infection, but have been relatively neglected in terms of hepatitis B virus vaccination. OBJECTIVES: In this study, compliance with hepatitis B vaccination among adult males with sexually diseases was examined. PATIENTS AND METHODS: In this survey, 114 males, referred to an infectious diseases clinic, were asked to complete a questionnaire evaluating their knowledge of hepatitis B vaccine, and were interviewed to assess their reasons for refusal or acceptance. Finally, SPSS (version 16) was used to perform the statistical analyses. Variables were analyzed with Chi-square tests. RESULTS: The results of this study indicated that the overall hepatitis B vaccine acceptance rate was acceptably high. Among all, 53.5% correctly identified that a vaccine to prevent hepatitis B virus infection had been available, 15% had a negative opinion, and 31.5% were neutral. The rations of all three doses of vaccination were 69.3%. CONCLUSIONS: Among the respondents, 87% were currently married, 86.8% were currently employed, 17.5% have addiction, 34.2 % used condom, and 36.8% correctly identified hepatitis B as a sexually transmitted infection.

Severe abdominal pain as the first manifestation of rabies.

INTRODUCTION: Rabies is an acute fatal viral disease that is generally transmitted from animals to humans following wild and domestic animal bites. The rabies virus enters the body from the area where the individual is bitten, and then the virus moves towards the brain and involves the nerves. CASE PRESENTATION: During the years 2001-2011, there have been 73 reported rabies cases. About 50,000 reported human deaths are annually due to rabies. The actual number of human deaths due to rabies in Asia especially India, Pakistan and Bangladesh are more than these numbers, since there is no advanced surveillance system for disease control to determine the actual number of infected and fatal human cases. According to the World Health Organization (WHO) reports, more than 10 million people who are bitten by animals are annually treated by prophylactic treatment regimens for rabies, worldwide. CONCLUSIONS: This paper reports on a case of human rabies with the first disease manifestation (severe abdominal pain). The patient reported extensive biting on his left leg by a dog. He had a slight fever of 38.1°C. It has been recommended that a careful history should be taken from patients for diagnosis of rabies disease. A complete history should be taken from patients for diagnosis of disease, because rabies could be wrong with various diseases with atypical symptoms. because various diseases with atypical symptoms or long incubation periods can visit.

Rare variants of cutaneous leishmaniasis presenting as eczematous lesions.

Cutaneous Leishmaniasis may present with clinical presentation such as zosteriform, sporotrichoid and erysipeloid. The eczema variant has rarely been reported. We report a 27- year- old patient with atypical cutaneous leishmaniasis resembling eczema on the hand of a man in Yazd province in the central of Iran.

Computer and Internet use among Undergraduate Medical Students in Iran.

OBJECTIVE: Although computer technologies are now widely used in medicine, little is known about its use among medical students in Iran. The aim of this study was to determine the competence and access to computer and internet among the medical students. METHODS: In this descriptive study, medical students of Shahid Sadoughi University of Medical Science, Yazd, Iran from the fifth years were asked to answer a questionnaire during a time-tabled lecture slot. The chi-square test was used to compare the frequency of computer and internet use between the two genders, and the level of statistical significance for all test was set at 0.05. RESULTS: All the students have a personal computer and internet access. There were no statistically significant differences between men and women for the computer and internet access, use wireless device to access internet, having laptop and e-mail address and the difficulties encountered using internet. The main reason for less utilization of internet was slow speed of data transfer. CONCLUSIONS: Because of the wide range of computer skills and internet information among medical students in our institution, a single computer and internet course for all students would not be useful nor would it be accepted.

Acceptability of HIV/AIDS testing among pre-marital couples in Iran (2012).

BACKGROUND: Human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) is a lifestyle-related disease. This disease is transmitted through unprotected sex, contaminated needles, infected blood transfusion and from mother to child during pregnancy and delivery. Prevention of infection with HIV, mainly through safe sex and needle exchange programmes is a solution to prevent the spread of the disease. Knowledge about HIV state helps to prevent and subsequently reduce the harm to the later generation. The purpose of this study was to assess the willingness rate of couples referred to the family regulation pre-marital counselling centre for performing HIV test before marriage in Yazd. PATIENTS AND METHODS: In this descriptive study, a simple random sampling was done among people referred to Akbari clinic. The couples were 1000 men and 1000 women referred to the premarital counselling centre for pre-marital HIV testing in Yazd in the year 2012. They were in situations of pregnancy, delivery or nursing and milking. The data were analyzed using Statistical Package for the Social Sciences (SPSS) software and chi-square statistical test. RESULTS: There was a significant statistical difference between the age groups about willingness for HIV testing before marriage (P < 0.001) and also positive comments about HIV testing in asymptomatic individuals (P < 0.001). This study also proved a significant statistical difference between the two gender groups about willingness to marry after HIV positive test of their wives. CONCLUSION: The willingness rate of couples to undergo HIV testing before marriage was significant. Therefore, HIV testing before marriage as a routine test was suggested.

Cutaneous leishmaniasis of the eyelid: a case report.

Cutaneous leishmaniasis is endemic in certain areas of Iran, and in recent years, there has been an increase in the number of reports for rare and new forms of cutaneous leishmaniasis. We describe one unusual clinical form of cutaneous leishmaniasis. In a 27-year-old man, who noted a pimple on the upper eyelid 4 months before. The lesion was nodular and measured 1 cm × 1 cm in diameter. A diagnosis of eyelid cutaneous leishmaniasis was made, and treatment was started with intramuscular meglumine antimonate. He showed a dramatic response, and the lesion almost completely disappeared.

Occupational hazards to dental staff.

Dental professionals are predisposed to a number of occupational hazards. These include exposure to infections (including Human Immunodeficiency Virus and viral hepatitis); percutaneous exposure incidents, dental materials, radiation, and noise; musculoskeletal disorders; psychological problems and dermatitis; respiratory disorders; and eye insults. Percutaneous exposure incidents remain a main concern, as exposure to serious infectious agents is a virtual risk. Minimizing percutaneous exposure incidents and their consequences should continue to be considered, including sound infection control practices, continuing education, and hepatitis B vaccination. Basically, for any infection control strategies, dentists should be aware of individual protective measures and appropriate sterilization or other high-level disinfection utilities. Strained posture at work disturbs the musculoskeletal alignment and leads to stooped spine. The stooped posture also involved certain groups of muscles and joints. This may lead to diseases of the musculoskeletal system. Continuous educating and appropriate intervention studies are needed to reduce the complication of these hazards. So, it is important for dentists to remain constantly up-to-date about measures on how to deal with newer strategies and dental materials, and implicates the need for special medical care for this professional group.