International journal of physiology, pathophysiology and pharmacology最新文献

Extracellular vesicles (EVs) have emerged as a captivating field of study in molecular biology with diverse applications in therapeutics. These small membrane-bound structures, released by cells into the extracellular space, play a vital role in intercellular communication and hold immense potential for advancing medical treatments. EVs, including exosomes, microvesicles, and apoptotic bodies, are classified based on size and biogenesis pathways, with exosomes being the most extensively studied. The aim of this study was to examine the molecular secretory pathway of exosomes and to discuss the medical applications of exosomes and the methods for employing them in laboratory models. The therapeutic potential of EVs has garnered significant attention. Their unique properties, such as stability, biocompatibility, and capacity to traverse biological barriers, make them promising vehicles for targeted drug delivery. By engineering EVs to carry specific cargo molecules, such as therapeutic proteins, small interfering Ribonucleic Acid (RNAs) (siRNAs), or anti-cancer drugs, researchers can enhance drug stability and improve their targeted delivery to specific cells or tissues. This approach has the potential to minimize off-target effects and increase therapeutic efficacy, offering a more precise and effective treatment strategy. EVs represent a captivating and rapidly evolving field with significant therapeutic implications. Their role in intercellular communication, targeted drug delivery, and regenerative medicine makes them valuable tools for advancing medical treatments. As our understanding of EV biology and their therapeutic applications continues to expand, we can expect remarkable advancements that will revolutionize the field of medicine and lead to more personalized and effective therapies.

Background: Patellofemoral osteoarthritis (PFOA) is a common cause of knee discomfort and impairment, particularly among athletes. The development of PFOA has been associated with anatomical knee variations, such as trochlear dysplasia and patella alta. However, the relationship between these anatomical variants and the development of PFOA remains poorly understood. This study aimed to investigate the association between PFOA and knee anatomical variants in a cohort of patients.

Methods: The study included 200 patients with PFOA and 200 healthy controls. In this study, we investigate the relationship of osteoarthritis with both anatomical variants and demographic characteristics. The participants underwent Magnetic resonance imaging (MRI) evaluation of the knee, and anatomical variants including trochlear dysplasia and patella alta were assessed. The severity of PFOA was also graded based on cartilage area and depth, as well as the bone marrow involvement and presence of osteophytes.

Results: Statistically significant differences were observed between the two groups in terms of Tibial tuberosity-trochlear groove (TT-TG) distance, patella position, trochlear dysplasia, and Insall-Salvati ratio. The mean TT-TG distance, prevalence of alta patella position, and Insall-Salvati ratio were significantly higher in cases (P<0.001 for all), and cases had a higher incidence of trochlear dysplasia (P<0.001). There were no significant differences between cases and controls regarding patella baja.

Conclusion: Anatomical knee variants, including the TT-TG distance, trochlear dysplasia, and Insall-Salvati ratio, are significant risk factors for PFOA progression. The results also indicate that higher BMI and older age are significantly associated with more measures of MRI Osteoarthritis Knee Score (MOAKS) than demographic information. Among anatomical variants, a higher TT-TG distance and an increased grade of trochlear dysplasia show a significant relationship with more measures of MOAKS. Understanding the relationship between these factors has important clinical and research implications and can help inform the development of new treatments.

Background: Following parapneumonic effusions, malignant pleural effusions (MPEs) stand as the second most common cause of exudative pleural effusions. These effusions typically remain unresponsive to systemic chemotherapy, necessitating novel therapeutic approaches. This study aims to ascertain the effectiveness of intrapleural injection with a 50% glucose solution and to compare it with intrapleural injection of Bleomycin sulfate in treating malignant pleural effusion.

Methods: This prospective, double-blind, randomized clinical trial was conducted at Al-Zahra Hospital in Isfahan. The study protocol gained approval from the Iranian Registry of Clinical Trials (IRCT code: IRCT20201013049017N1) (https://en.irct.ir/trial/52739). The study population encompassed patients with malignant pleural effusion. Sampling occurred through a census approach from October 2019 to March 2020. The first group received a pleurodesis solution containing 12.5 cc of 2% lidocaine with Bleomycin, while the second group received a solution comprising 200 cc of 50% glucose solution (10 grams of glucose) and 12.5 ml of 2% lidocaine, within the same volume. These solutions were injected into the pleural space via the chest tube.

Results: The complete response rate to treatment three months post-injection was 71.9% in the Bleomycin sulfate group and 65.6% in the 50% dextrose group. However, the difference between the two groups did not achieve statistical significance (P = 0.689). The incidence of post-injection fever and pain intensity exhibited comparability in both groups.

Conclusion: The treatment involving a combination of 50% glucose solution with Bleomycin for pleurodesis in patients with malignant pleural effusion demonstrated outcomes akin to other treatment options.

Objective: Determine the effect of different spectrum laser radiations on the expression of Glial Fibrillary Acidic Protein (GFAP) and allograft inflammatory factor-1 (Iba-1) in the sciatic nerve during regeneration.

Methods: The experiment was performed on 60 lab Wistar rats weighing 200-250 g. The left sciatic nerve was severed and subsequent end-to-end epineural suturing was performed 10, 20, 30, and 45 minutes after neurotomy. Western blot and immunohistochemistry analyses were performed by means of polyclonal anti-GFAP antibodies (Thermo Fisher Scientific, USA) and anti-Iba-1 antibodies (Invitrogen, USA) 90 days after nerve repair.

Results: The use of green and blue spectrum laser radiation significantly increased GFAP protein expression regardless of the time when surgical nerve repair was performed after injury. The expression of Iba-1 and tubulin after blue spectrum laser radiation with a wavelength of 470 nm was significantly higher than the control values by 5.1-11.0 times. An increase in the expression of Iba-1 and tubulin was noted when a green spectrum laser with a wavelength of 560 nm was utilized and nerve suturing was performed 10 and 20 minutes after nerve injury. The green spectrum laser with a wavelength of 520 nm had no significant effect on the expression of Iba-1 and tubulin. Morphologically, the highest proliferative reaction of glia was recorded when using a blue spectrum laser.

Conclusions: Laser radiation with blue (470 nm) and green (560 nm) spectra, promoted the activation of GFAP-positive Schwann cells and nerve regeneration. Activation of microglia is a necessary component of nerve regeneration and the content of Iba-1 represented the efficiency of regeneration.

Background: Sleep disorders can significantly impair the quality of life and daily functions. Evaluating sleep quality can provide valuable information about working conditions. This study aims to evaluate the sleep quality of faculty members at Isfahan University of Medical Sciences (IUMS).

Methods: This descriptive-analytic study was conducted from 2020 to 2021, involving 106 faculty members from the medical school. A questionnaire collected demographic information, including age, sex, height, weight, body mass index (BMI), level of education, history of faculty membership, major, working hours during the day and night, residency place, and medical history. The Pittsburgh Sleep Quality Index (PSQI) and Symptom Checklist-25 (SCL-25) questionnaire were used to assess participants' sleep quality. Data were compared between clinicians and basic science faculty members.

Results: PSQI subtypes were examined among the participants. The total PSQI score was 6.20±3.4. A comparison of PSQI scores and subtypes based on age categories did not show any significant differences (P > 0.05 for all). Clinicians had significantly lower total PSQI scores (P=0.044), sleep latency (P=0.024), sleep disturbances (P=0.012), and daytime dysfunction (P=0.022). Additionally, clinicians had a lower severity of sleep latency (P=0.024), sleep disturbances (P=0.012), and total PSQI score (P=0.044). However, clinicians exhibited a higher intensity of daytime dysfunction (P=0.022).

Conclusion: Faculty members exhibited a high prevalence of sleep disorders, with the most common disorders being sleep disturbance and high sleep latency. The prevalence of sleep disorders was higher among basic science faculty members compared to clinicians.

Obstructive sleep apnea (OSA) is a sleep disorder of significant health concern with a high prevalence in the general population. It has been found to exhibit a high incidence of comorbidity with epilepsy, the exact underlying pathophysiology of which still remains poorly understood. OSA is characterized by apnea/hypopnea spells and arousals, leading to intermittent hypoxemia and sleep deprivation. Both sleep deprivation and hypoxemia adversely affect the cortical excitability and favor epileptogenesis and worsening of pre-existing epilepsy, if any. In patients with OSA, deprivation of rapid eye movement sleep (REMS) phase (known for its strong antiepileptic influence) is relatively more than that non rapid eye movement sleep phase leading to postulation of REMS deprivation as a significant factor in the development of epilepsy as a comorbidity in patients with OSA. Furthermore, OSA and epilepsy both have shown to exercise a bidirectional influence on one another and are also likely to exacerbate each other through a positive feedback mechanism. This is especially based on the reports of improved control of epilepsy upon treatment of comorbid OSA. This brief paper attempts to present an underlying pathophysiological basis of the comorbidity of OSA and epilepsy based upon sleep deprivation and hypoxemia that are characteristic features observed in patients with OSA.

There is conflicting data regarding the ability of nitric oxide (NO) to promote or inhibit colorectal cancer cell proliferation. Furthermore, NO reacts rapidly with endogenous superoxide at a diffusion-controlled rate to give peroxynitrite (ONOO^-), a strong oxidant and nitrating agent. The aim of this study was to assess the effects of exogenous NO and ONOO^- on the proliferation of the colorectal cancer cell line Caco-2. NOR5 and SIN-1 were used as NO and ONOO^- donors, respectively. Both NOR5 and SIN-1 inhibited the proliferation of the Caco-2 cells; however, the effect of NOR5 was slightly stronger than that of SIN-1. The results also indicated that NO plays a major role in the inhibition of SIN-1-induced proliferation of Caco-2 cells. The results of a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, cell cycle analysis, and p21 protein expression measurement further indicated that NO induced S-G₂/M phase arrest, but not apoptosis, in the Caco-2 cells. The results suggest that NO, rather than ONOO^-, has the potential to repress the proliferation of Caco-2 cells by inducing S-G₂/M cell cycle arrest.

Alcohol consumption afflicts men and women differently. However, the underlying neuronal mechanisms that contribute to the difference are mostly unexplored. Although more men suffer from alcohol use disorders (AUD), women more frequently accelerate to dependence and develop adverse consequences of alcoholism sooner than men. Women also exhibit more significant negative emotions that cues more reactivity and alcohol-craving than men. Despite ample evidence that women are vulnerable to AUD, results of preclinical studies on sex differences in alcohol consumption and withdrawal-related behaviors are inconclusive. In this study, we trained adult male and female Sprague-Dawley rats to drink alcohol in the intermittent access to 20% ethanol two-bottle free-choice paradigm for two months. Their behaviors and Fos expression in related brain regions were measured at acute (24 h) and after prolonged (28 days) abstinence. We found that female rats drank more alcohol than males. After acute abstinence, rats of both sexes showed higher sensitivity to depressive, thermal, and mechanical stimuli. Females also displayed higher anxiety levels. After prolonged abstinence, rats of both sexes displayed depressive-like behaviors; the males displayed allodynia; the females showed higher anxiety levels and drank more alcohol upon reaccess to alcohol. Furthermore, during acute withdrawal, Fos-positive nuclei were increased in the prefrontal cortex, anterior cingulate cortex (ACC), nucleus accumbens (NAc), amygdala and lateral habenula (LHb) in the females, versus only in the ACC, amygdala, and LHb in the males. Conversely, after prolonged abstinence, Fos-positive nuclei were decreased in the prefrontal cortex, ACC, and NAc in the females, but fell in the ACC, NAc, and LHb of the males. Thus, adaptations in diverse brain regions may contribute to the sex differences in behaviors in ethanol-withdrawn rats.

Multiple Sclerosis (MS) is an autoimmune, inflammatory disease of the central nervous system (CNS) mostly affecting young adults. The exact mechanism and pathogenesis of MS remain still undiscovered but there have been useful treatments with different efficacy rates. Most of these therapies are divided into the first line, second line and third line, impact on the immune system and immune cells. These drugs are approved to be useful in MS, but like any other therapies, adverse effects (AE) are associated with these drugs. In this review, we continue the survey over mechanisms of actions and AEs of MS drugs. Physicians must be aware of such AEs and complications to choose the best drug for each patient.

Diabetes mellitus has been recognised as one of the four major non-communicable diseases that demands urgent attention from all key shareholders globally in an effort to address its prevalence and associated complications. It is considered as a top 10 cause of death globally, killing about 1.6 million people worldwide and is seen as the third highest risk factor for worldwide premature mortality due to hyperglycaemia and hyperglycaemic-induced oxidative stress and inflammation. There is a strong link between hyperglycaemia, hyperglycaemic-induced oxidative stress, inflammation and the development and progression of type 2 diabetes mellitus. Various reports have shown that chronic low-grade inflammation is associated with the risk of developing type 2 diabetes and that sub-clinical inflammation contributes to insulin resistance and is linked to the characteristics of metabolic syndrome which include hyperglycaemia. Oxidative stress stimulates the generation of inflammatory mediators and inflammation in turn enhances the production of reactive oxygen species. This interaction between diabetes, oxidative stress and inflammation is the primary motivation for the compilation of this review. Based on previous studies, the review examines the interaction between diabetes, oxidative stress and inflammation, factors promoting prevalence of diabetes mellitus, mechanisms involved in hyperglycaemia-induced oxidative stress with particular focus on type 2 diabetes and selected diabetic complications.