Advances in glioblastoma multiforme: Integrating therapy and pathology perspectives.

Glioblastoma, a highly lethal form of brain cancer, is characterized by its aggressive growth and resistance to conventional treatments, often resulting in limited survival. The response to therapy is notably influenced by various patient-specific genetic factors, underscoring the disease's complexity. Despite the utilization of diverse treatment modalities such as surgery, radiation, and chemotherapy, many patients experience local relapse, emphasizing the critical need for improved therapeutic strategies to effectively target these formidable tumors. Recent years have witnessed a surge in interest in natural products derived from plants, particularly alkaloids, for their potential anticancer effects. Alkaloids have shown promise in cancer chemotherapy by selectively targeting crucial signaling pathways implicated in tumor progression and survival. Specifically, they modulate the NF-κB and MAPK pathways, resulting in reduced tumor growth and altered gene expression across various cancer types. Additionally, alkaloids exhibit the capacity to induce cell cycle arrest, further impeding tumor proliferation in several malignancies. This review aims to delineate recent advances in understanding the pathology of glioblastoma multiforme (GBM) and to explore the potential therapeutic implications of alkaloids in managing this deadly disease. By segregating discussions on GBM pathology from those on alkaloid-based therapies, we provide a structured overview of the current challenges in GBM treatment and the promising opportunities presented by alkaloid-based interventions. Furthermore, we briefly discuss potential future directions in GBM research and therapy beyond alkaloids, including emerging treatment modalities or areas of investigation that hold promise for improving patient outcomes. In conclusion, our efforts offer hope for enhanced outcomes and improved quality of life for GBM patients through alkaloid-based therapies. By integrating insights from pathology and therapeutic perspectives, we underscore the significance of a comprehensive approach in addressing this devastating disease.

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.

How gallic acid regulates molecular signaling: role in cancer drug resistance.

Cancer is one of the deadliest and most heterogeneous diseases. Cancers often develop drug resistance, which can lead to treatment failure or recurrence. Accordingly, anticancer compounds are essential for chemotherapy-resistant cancer cells. Phenolic compounds are of interest in the development of cancer drugs due to their medicinal properties and ability to target different molecular pathways. Gallic acid (GA), as one of the main components of phenol, which is abundantly present in plant compounds such as walnut, sumac, grapes, tea leaves, oak bark, and other plant compounds, has antitumor properties. GA can prevent cancer progression, cell invasion, and metastasis by targeting molecular pathways and is an effective complement to chemotherapy drugs and combating multidrug resistance (MDR). In this review, we discuss various mechanisms related to cancer, the therapeutic potential of GA, the antitumor properties of GA in various cancers, and the targeted delivery of GA with nanocarriers.

Photonic nanoparticles: emerging theranostics in cancer treatment.

This review explores the potential of photonic nanoparticles for cancer theranostics. Photonic nanoparticles offer unique properties and photonics capabilities that make them promising materials for cancer treatment, particularly in the presence of near-infrared light. However, the size of the particles is crucial to their absorption of near-infrared light and therapeutic potential. The limitations and challenges associated with the clinical use of photonic nanoparticles, such as toxicity, immune system clearance, and targeted delivery to the tumor are also discussed. Researchers are investigating strategies such as surface modification, biodegradable nanoparticles, and targeting strategies to improve biocompatibility and accumulation in the tumor. Ongoing research suggests that photonic nanoparticles have potential for cancer theranostics, further investigation and development are necessary for clinical use.

Tiny particles called 'photonic nanoparticles' can be used to help treat cancer. These particles have special properties that allow them to be used with special light to treat cancer. However, the size of the particles is really important, so scientists are trying to find ways to make sure they are the right size. There are also some challenges with using these particles in people, like making sure they don't harm the body and that they go to the right place. Scientists are working on ways to improve the safety of these particles and make sure they go where they need to.

Resveratrol regulates inflammation and improves oxidative stress via Nrf2 signaling pathway: Therapeutic and biotechnological prospects.

Usually, in aerobic metabolism, natural materials including nucleic acids, proteins, and lipids can experience auxiliary injury by oxidative responses. This damage produced by reactive oxygen/nitrogen species has been identified as "oxidative stress." As a natural polyphenol got from red wine and peanuts, resveratrol is one of the most eminent anti-aging mixtures. Based on many studies', resveratrol hinders destructive effects of inflammatory causes and reactive oxygen radicals in several tissues. The nuclear erythroid 2-related factor 2 is a factor related to transcription with anti-inflammatory, antioxidant possessions which is complicated by enzyme biotransformation and biosynthesis of lipids and carbohydrates. This review provides current understanding and information about the character of resveratrol against oxidative stress and regulation of inflammation via Nrf2 signaling pathway.

The Role of NRF2/KEAP1 Pathway in Glioblastoma: Pharmacological Implications.

Glioblastoma multiforme (GBM) grade IV glioma is the most frequent and deadly intracranial cancer. This tumor is determined by unrestrained progression, uncontroled angiogenesis, high infiltration and weak response to treatment, which is chiefly because of abnormal signaling pathways in the tumor. A member related to the Cap 'n' collar family of keypart-leucine zipper transcription agents-the transcription factor NF-E2-related factor 2 (Nrf2)-regulates adaptive protection answers by organized upregulation of many genes that produce the cytoprotective factors. In reply to cellular pressures types such as stresses, Nrf2 escapes Kelch-like ECH-related protein 1 (Keap1)-facilitated suppression, moves from the cytoplasm towards the nucleus and performs upregulation of gene expression of antioxidant responsive element (ARE). Nrf2 function is related tocontrolling many types of diseases in the human specially GBM tumor.Thus, we will review the epigeneticalregulatory actions on the Nrf2/Keap1 signaling pathway and potential therapeutic options in GBM by aiming the stimulation of Nrf2.

Targeting LIN28: a new hope in prostate cancer theranostics.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.

Overview of key molecular and pharmacological targets for diabetes and associated diseases.

Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.

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.

Mesenchymal Stem Cell Derived-Exosomes as Effective Factors in Reducing Cytokine Storm Symptoms of COVID-19.

Given that conventional therapies are ineffective for COVID-19, obtained exosomes from stem cells have been proposed as a sustainable and effective treatment. Exosomes are subsets with lengths between 30 and 100 nanometers, and they can be secreted by different cells. Exosomes are containing different types of miRNAs, mRNAs, and different proteins. The role of immune system modulation of exosomes of mesenchymal stem cells has been studied and confirmed in more than one study. Exosome miRNAs detect and reduce cytokines that cause cytokine storms such as IL-7, IL-2, IL-6, etc. These miRNAs include miR-21, miR-24, miR-124, miR-145, etc. The risks associated with treatment with exosomes from different cells are relatively small compared to other treatments because transplanted cells do not stimulate the host immune system and also has reduced infection transmission. Due to the ineffectiveness of existing drugs in reducing inflammation and preventing cytokine storms, the use of immune-boosting systems may be suggested as another way to control cytokine storm.

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.

Comparison of Chronic Obstructive Pulmonary Diseases Induced by Wood Smoke and Tobacco Smoke.

Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation and decline in lung function. Although tobacco smoke is the leading risk factor for COPD, air contamination by wood-burning smoke is also of great concern. About half of the world's populations, especially in developing countries such as Iran, exploit this energy source for cooking and heating. It is remained unknown if COPD induced by wood smoke from baking bread (COPD-B) and COPD induced by tobacco smoke (COPD-S) have different symptoms and clinical presentations. To fill this gap, the present study was to describe such differences. Materials and Methods: This retrospective cohort study was performed in Afshar COPD clinics affiliated with the Shahid Sadoughi University of Medical Sciences, Yazd, Iran. The clinical records of 231 patients with the COPD diagnosis were reviewed. After considering inclusion and exclusion criteria, 91 patients (46 with COPD -B and 45 with COPD-S) underwent physical examination and para-clinical assessments (i.e., respiratory function tests, Chest X-ray, and quality of life test). Results: The COPD-B patients were mainly women at older age and had higher FEV 1 /FVC and FEF-75; however, they had fewer post-bronchodilator positive responses to FEV 1 (suggesting a restriction pattern) and sputum production, compared to the COPD-S patients. Regarding the other parameters, there were no statistically significant differences between the two groups. Conclusion: This was the first study evaluating and revealing some differences in the clinical and paraclinical characteristics of the COPD-B patients (with prolonged exposure to wood smoke from bread baking; >100 hours per year, for at least 10 years) and COPD-S patients (>10 packs per year of exposure to tobacco smoke).

Therapeutic Potential of Curcumin in the Treatment of Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor. Despite standard multimodality treatment, the highly aggressive nature of GBM makes it one of the deadliest human malignancies. The anti-cancer effects of dietary phytochemicals like curcumin provide new insights to cancer treatment. Evaluation of curcumin's efficacy against different malignancies including glioblastoma has been a motivational research topic and widely studied during the recent decade. In this review, we discuss the recent observations on the potential therapeutic effects of curcumin against glioblastoma. Curcumin can target multiple signaling pathways involved in developing aggressive and drug-resistant features of glioblastoma, including pathways associated with glioma stem cell activity. Notably, combination therapy with curcumin and chemotherapeutics like temozolomide, the GBM standard therapy, as well as radiotherapy has shown synergistic response, highlighting curcumin's chemo- and radio-sensitizing effect. There are also multiple reports for curcumin nanoformulations and targeted forms showing enhanced therapeutic efficacy and passage through blood-brain barrier, as compared with natural curcumin. Furthermore, in vivo studies have revealed significant anti-tumor effects, decreased tumor size and increased survival with no notable evidence of systemic toxicity in treated animals. Finally, a pharmacokinetic study in patients with GBM has shown a detectable intratumoral concentration, thereby suggesting a potential for curcumin to exert its therapeutic effects in the brain. Despite all the evidence in support of curcumin's potential therapeutic efficacy in GBM, clinical reports are still scarce. More studies are needed to determine the effects of combination therapies with curcumin and importantly to investigate the potential for alleviating chemotherapy- and radiotherapy-induced adverse effects.

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.

Diagnostic value of sputum adenosine deaminase (ADA) level in pulmonary tuberculosis.

INTRODUCTION: Tuberculosis is still a considerable health problem in many countries. Rapid diagnosis of this disease is important, and adenosine deaminase (ADA) has been used as a diagnostic test. The aim of this study was to assess the diagnostic value of ADA in the sputum of patients with pulmonary tuberculosis. METHODS: The current study included 40 patients with pulmonary tuberculosis (culture positive, smear ±) and 42 patients with non tuberculosis pulmonary diseases (culture negative). ADA was measured on all of the samples. RESULTS: The median value of ADA in non-tuberculosis patients was 2.94 (4.2) U/L and 4.01 (6.54) U/L in tuberculosis patients, but this difference was not statistically significant (p=0.100). The cut-off point of 3.1 U/L had a sensitivity of 61% and a specificity of 53%, the cut-off point of 2.81 U/L had a sensitivity of 64% and a specificity of 50% and the cut-off point of 2.78 U/L had a sensitivity of 65% and a specificity of 48%. The positive predictive values for cut-off points of 3.1, 2.81 and 2.78 U/L were 55.7%, 57.44% and 69.23%, respectively. The negative predictive values for the abovementioned cut-off points were 56.75%, 57.14% and 55.88%, respectively. CONCLUSION: Our results showed that sputum ADA test is neither specific nor sensitive. Because of its low sensitivity and specificity, determination of sputum ADA for the diagnosis of pulmonary tuberculosis is not recommended.

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.