Therapeutic Targeting of Krüppel-Like Factor 4 and Its Pharmacological Potential in Parkinson's Disease: a Comprehensive Review.

Krüppel-like factor 4 (KLF4), a zinc finger transcription factor, is found in different human tissues and shows diverse regulatory activities in a cell-dependent manner. In the brain, KLF4 controls various neurophysiological and neuropathological processes, and its contribution to various neurological diseases has been widely reported. Parkinson's disease (PD) is an age-related neurodegenerative disease that might have a connection with KLF4. In this review, we discussed the potential implication of KLF4 in fundamental molecular mechanisms of PD, including aberrant proteostasis, neuroinflammation, apoptosis, oxidative stress, and iron overload. The evidence collected herein sheds new light on KLF4-mediated pathways, which manipulation appears to be a promising therapeutic target for PD management. However, there is a gap in the knowledge on this topic, and extended research is required to understand the translational value of the KLF4-oriented therapeutical approach in PD.

Breast feeding, obesity, and asthma association: clinical and molecular views.

Asthma is a chronic condition that affects children worldwide. Accumulating number of studies reported that the prevalence of pediatric obesity and asthma might be altered through breastfeeding. It has been proposed that Leptin, which exists in human milk, is oppositely associated with weight increase in newborns. It may also influence peripheral immune system by promoting TH1 responses and suppressing TH2 cytokines. Leptin influences body weight and immune responses through complex signaling pathways at molecular level. Although previous studies provide explanations for the protective role of breastfeeding against both obesity and asthma, other factors such as duration of breastfeeding, parental, and prenatal factors may confound this relationship which requires further research.

A narrative review of the effects of dexamethasone on traumatic brain injury in clinical and animal studies: focusing on inflammation.

Traumatic brain injury (TBI) is a type of brain injury resulting from a sudden physical force to the head. TBI can range from mild, such as a concussion, to severe, which might result in long-term complications or even death. The initial impact or primary injury to the brain is followed by neuroinflammation, excitotoxicity, and oxidative stress, which are the hallmarks of the secondary injury phase, that can further damage the brain tissue. Dexamethasone (DXM) has neuroprotective effects. It reduces neuroinflammation, a critical factor in secondary injury-associated neuronal damage. DXM can also suppress the microglia activation and infiltrated macrophages, which are responsible for producing pro-inflammatory cytokines that contribute to neuroinflammation. Considering the outcomes of this research, some of the effects of DXM on TBI include: (1) DXM-loaded hydrogels reduce apoptosis, neuroinflammation, and lesion volume and improves neuronal cell survival and motor performance, (2) DXM treatment elevates the levels of Ndufs2, Gria3, MAOB, and Ndufv2 in the hippocampus following TBI, (3) DXM decreases the quantity of circulating endothelial progenitor cells, (4) DXM reduces the expression of IL1, (5) DXM suppresses the infiltration of RhoA + cells into primary lesions of TBI and (6) DXM treatment led to an increase in fractional anisotropy values and a decrease in apparent diffusion coefficient values, indicating improved white matter integrity. According to the study, the findings show that DXM treatment has neuroprotective effects in TBI. This indicates that DXM is a promising therapeutic approach to treating TBI.

Clinical characteristics and prognosis of temporary miller fisher syndrome following COVID-19 vaccination: a systematic review of case studies.

BACKGROUND: Miller Fisher syndrome (MFS) is a subtype of Guillain-Barré syndrome (GBS) which is characterized by the three components of ophthalmoplegia, ataxia, and areflexia. Some studies reported MFS as an adverse effect of the COVID-19 vaccination. We aimed to have a detailed evaluation on demographic, clinical, and para-clinical characteristics of subjects with MFS after receiving COVID-19 vaccines. MATERIALS AND METHODS: A thorough search strategy was designed, and PubMed, Web of Science, and Embase were searched to find relevant articles. Each screening step was done by twice, and in case of disagreement, another author was consulted. Data on different characteristics of the patients and types of the vaccines were extracted. The risk of bias of the studies was assessed using Joanna Briggs Institute (JBI) tools. RESULTS: In this study, 15 patients were identified from 15 case studies. The median age of the patients was 64, ranging from 24 to 84 years. Ten patients (66.6%) were men and Pfizer made up 46.7% of the injected vaccines. The median time from vaccination to symptoms onset was 14 days and varied from 7 to 35 days. Furthermore,14 patients had ocular signs, and 78.3% (11/14) of ocular manifestations were bilateral. Among neurological conditions, other than MFS triad, facial weakness or facial nerve palsy was the most frequently reported side effect that was in seven (46.7%) subjects. Intravenous immunoglobulin (IVIg) was the most frequently used treatment (13/15, 86.7%). Six patients received 0.4 g/kg and the four had 2 g/kg. Patients stayed at the hospital from five to 51 days. No fatal outcomes were reported. Finally, 40.0% (4/15) of patients completely recovered, and the rest experienced improvement. CONCLUSION: MFS after COVID-19 immunization has favorable outcomes and good prognosis. However, long interval from disease presentation to treatment in some studies indicates that more attention should be paid to MFS as the adverse effect of the vaccination. Due to the challenging diagnosis, MFS must be considered in list of the differential diagnosis in patients with a history of recent COVID-19 vaccination and any of the ocular complaints, ataxia, or loss of reflexes, specially for male patients in their 60s and 70s.

Targeting Nrf2 signaling pathway by quercetin in the prevention and treatment of neurological disorders: An overview and update on new developments.

BACKGROUND: Neurological disorders (NLDs) are widely acknowledged as a significant public health concern worldwide. Stroke, Alzheimer's disease (AD), and traumatic brain injury (TBI) are three of these disorders that have sparked major study attention. Neurological dysfunction, protein buildup, oxidation and neuronal injury, and aberrant mitochondria are all prevalent neuropathological hallmarks of these disorders. The signaling cascade of nuclear factor erythroid 2 related factor 2 (Nrf2) shares all of them as a common target. Several studies have found that overexpression of Nrf2 is a promising treatment method in NLDs. Effective treatment of these disorders continues to be a universal concern regardless of various medicines. In order to treat a variety of neurological problems, organic remedies may provide an alternative treatment. It has been demonstrated that polyphenols like quercetin (Que) offer considerable capabilities for treating NLDs. One of Que's greatest key targets, Nrf2, has the capacity to control the production of a number of cytoprotective enzymes that exhibit neuroprotective, detoxifying, and antioxidative effects. Additionally, Que enhanced the expression of Nrf2 and inhibited alterations in the shape and death of neurons in the hippocampus. OBJECTIVE: In this review, we have focused on Que's medicinal prospects as a neuroprotective drug. METHODS: PubMed, Scopus, Science Direct, and Google Scholar were used to search articles for this study. RESULTS: The findings of this research demonstrate that (1) Que protected the blood-brain barrier via stimulating Nrf2 in animal stroke, which alleviated ischemic reperfusion and motor dysfunction. (2) By triggering the Nrf2 pathway, Que reduced the neuroinflammation and oxidative damage brought on by TBI in the cortex. (3) In an experimental model of AD, Que enhanced cognitive function by decreasing A1-4, antioxidant activity, and Nrf2 levels in the brain. CONCLUSION: We discuss recent research on Que-mediated Nrf2 expression in the management of several NLDs in this paper.

Targeting Nrf2 signaling pathway and oxidative stress by resveratrol for Parkinson's disease: an overview and update on new developments.

Parkinson's disease (PD) as a prevalent neurodegenerative condition impairs motor function and is caused by the progressive deterioration of nigrostriatal dopaminergic (DAergic) neurons. The current therapy solutions for PD are ineffective because they could not inhibit the disease's progression and they even have adverse effects. Natural polyphenols, a group of phytochemicals, have been found to offer various health benefits, including neuroprotection against PD. Among these, resveratrol (RES) has neuroprotective properties owing to its capacity to protect mitochondria and act as an antioxidant. An increase in the formation of reactive oxygen species (ROS) leads to oxidative stress (OS), which is responsible for cellular damage resulting in lipid peroxidation, oxidative protein alteration, and DNA damage. In PD models, it's been discovered that RES pretreatment can diminish oxidative stress by boosting endogenous antioxidant status and directly scavenging ROS. Several studies have examined the involvement of RES in the modulation of the transcriptional factor Nrf2 in PD models because this protein recognizes oxidants and controls the antioxidant defense. In this review, we have examined the molecular mechanisms underlying the RES activity and reviewed its effects in both in vitro and in vivo models of PD. The gathered evidence herein showed that RES treatment provides neuroprotection against PD by reducing OS and upregulation of Nrf2. Moreover, in the present study, scientific proof of the neuroprotective properties of RES against PD and the mechanism supporting clinical development consideration has been described.

Human T2R38 Bitter Taste Receptor Expression and COVID-19: From Immunity to Prognosis.

Background: Bitter taste-sensing type 2 receptor (T2Rs or TAS2Rs) found on ciliated epithelial cells and solitary chemosensory cells have a role in respiratory tract immunity. T2Rs have shown protection against SARS-CoV-2 by enhancing the innate immune response. The purpose of this review is to outline the current sphere of knowledge regarding this association. Methods: A narrative review of the literature was done by searching (T2R38 OR bitter taste receptor) AND (COVID-19 OR SARS-CoV-2) keywords in PubMed and google scholar. Results: T2R38, an isoform of T2Rs encoded by the TAS2R38 gene, may have a potential association between phenotypic expression of T2R38 and prognosis of COVID-19. Current studies suggest that due to different genotypes and widespread distributions of T2Rs within the respiratory tract and their role in innate immunity, treatment protocols for COVID-19 and other respiratory diseases may change accordingly. Based on the phenotypic expression of T2R38, it varies in innate immunity and host response to respiratory infection, systemic symptoms and hospitalization. Conclusion: This review reveals that patients' innate immune response to SARS-COV-2 could be influenced by T2R38 receptor allelic variations.

A comprehensive view on the quercetin impact on bladder cancer: Focusing on oxidative stress, cellular, and molecular mechanisms.

Bladder cancer (BC) is known as a prevalent genitourinary malignancy and has a significant mortality rate worldwide. Despite recent therapeutic approaches, the recurrence rate is high, highlighting the need for a new strategy to reduce the BC cell progression. Quercetin, a flavonoid compound, demonstrated promising anticancer properties and could be used in the management of various malignancies such as BC. This comprehensive review summarized quercetin's cellular and molecular mechanisms underlying anticancer activities. The study's findings indicated that quercetin prevents the proliferation of the human BC cell line, promotes apoptosis of BIU-87 cells, reduces the expression of p-P70S6K, and induces apoptosis by p-AMPK. Moreover, quercetin restricts tumor growth through the AMPK/mTOR cascade and prevents colony formation of human BC cells by triggering DNA damage. Studying this review article will help researchers better understand quercetin's functional role in the prevention and treatment of BC.

Curcumin effects on chronic obstructive pulmonary disease: A systematic review.

Introduction: Chronic obstructive pulmonary disease (COPD) is a common disease of the lungs known as the third reason for death worldwide. Frequent COPD exacerbations compel health care workers to apply interventions that are not adverse effect free. Accordingly, adding or replacing Curcumin, a natural meal flavoring, may indicate advantages in this era by its antiproliferative and anti-inflammatory effects. Methods: The PRISMA checklist was employed for the systematic review study. On June 3, 2022, PubMed/Medline, Scopus, and Web of Science were searched for studies associated with COPD and Curcumin in the last 10 years. Duplicate or non-English publications and articles with irrelevant titles and abstracts were excluded. Also, preprints, reviews, short communications, editorials, letters to the editor, comments, conference abstracts, and conference papers were not included. Results: Overall, 4288 publications were found eligible, after the screening, 9 articles were finally included. Among them, one, four, and four in vitro, in vivo, and both in vivo and in vitro research exist respectively. According to the investigations, Curcumin can inhibit alveolar epithelial thickness and proliferation, lessen the inflammatory response, remodel the airway, produce ROS, alleviate airway inflammation, hinder emphysema and prevent ischemic complications. Conclusion: Consequently, the findings of the current review demonstrate that Curcumin's modulatory effects on oxidative stress, cell viability, and gene expression could be helpful in COPD management. However, for data confirmation, further randomized clinical trials are required.

Gemfibrozil, a lipid-lowering drug, improves hepatorenal damages in a mouse model of aging.

Gemfibrozil (GFZ) is a medication of the fibrate category with agonistic effects on peroxisome proliferator-activated receptor-α (PPAR-α) and is effective for hypertriglyceridemia and mixed dyslipidemia. This agent also has anti-inflammatory and antioxidant properties. The current study investigated the effects of GFZ on hepatorenal damages in a D-galactose (D-gal)-induced aging model. We used 28 male mice, which were equally and randomly divided into four groups as follows: normal, D-gal (150 mg/kg/day; intraperitoneal [i.p.], for 6 weeks), GFZ (100 mg/kg/day GFZ, orally [p.o.] for 6 weeks), and the combined D-gal + GFZ. Liver and kidney function indices were measured as serum creatinine, blood urine nitrogen, alanine aminotransferase, and aspartate aminotransferase. Oxidative stress in hepatic and renal tissue was evaluated through malondialdehyde, superoxide dismutase, and glutathione peroxidase levels. Finally, the liver and kidney tissues were assessed for histopathological lesions. The results showed that D-gal-induced aging leads to abnormalities in liver and kidney function indices. D-gal also induced significant oxidative stress and histopathological lesions in these organs. GFZ improved function indices and oxidative stress compared to the D-gal-treated animals. Histological evaluations of the liver and kidney also confirmed these results. These data provide evidence for the potential therapeutic of GFZ in clinical practice for mitigating the hepatorenal damages of aging.

Changes in lifestyle behaviour and dietary patterns among Iranian medical students during COVID-19 lockdown.

Background: The COVID-19 pandemic has affected many aspects of human life, including physical and mental health. The public health measures to prevent COVID-19 transmission led to social isolation, physical inactivity, anxiety, depression, sleep disorders, obesity, and consumption of unhealthy food. Aims: To evaluate changes in lifestyle behaviour during the fifth wave of COVID-19 in Iranian medical students. Methods: This was a cross-sectional descriptive study. In September 2021, an online questionnaire containing 32 questions was administered to 1143 medical students in Teheran universities. Some 286 completed copies of the questionnaire were excluded because of incomplete answers. Descriptive statistics of central tendency measures and dispersion were used and independent t-test and a Chi-square test between two variables were conducted. Statistical analysis was performed using SPSS version 24. Results: A total of 462 (53.9%) students had COVID-19 during the fifth wave of the disease, 657 (76.7%) were deprived of social and sports activities, and 278 (32.4%) had difficulty completing their academic studies. Students who took vitamin supplements experienced lower levels of stress and 711 (83.0%) reported bodyweight change. There were significant relationships between bodyweight change, stress level and hospitalization due to COVID-19. There was a significant relationship between smoking, bodyweight change and hospitalization rate. A total of 426 (50.3%) students did not have a regular sleep-wake pattern, 701 (81.8%) spent more time using social media, 197 (23.0%) consumed more fast food, and 674 (78.6%) experienced stress or anxiety. Conclusion: There was an increased tendency towards unhealthy lifestyle among medical students in Tehran during COVID-19 lockdown. These findings can be useful in assessing lifestyle behaviours among students and in planning for improvements.