Pathophysiology, Volume 30, Issue 1 (March 2023) – 7 articles

Cells employ a well-preserved physiological stress response mechanism, termed the heat shock response, to activate a certain type of molecular chaperone called heat shock proteins (HSPs). HSPs are activated by transcriptional activators of heat shock genes known as heat shock factors (HSFs). These molecular chaperones are categorized as the HSP70 superfamily, which includes HSPA (HSP70) and HSPH (HSP110) families; the DNAJ (HSP40) family; the HSPB family (small heat shock proteins (sHSPs)); chaperonins and chaperonin-like proteins; and other heat-inducible protein families. HSPs play a critical role in sustaining proteostasis and protecting cells against stressful stimuli. HSPs participate in folding newly synthesized proteins, holding folded proteins in their native conformation, preventing protein misfolding and accumulation, and degrading denatured proteins. Ferroptosis is a recently identified type of oxidative iron-dependent cell demise. It was coined recently in 2012 by Stockwell Lab members, who described a special kind of cell death induced by erastin or RSL3. Ferroptosis is characterized by alterations in oxidative status resulting from iron accumulation, increased oxidative stress, and lipid peroxidation, which are mediated by enzymatic and non-enzymatic pathways. The process of ferroptotic cell death is regulated at multiple, and it is involved in several pathophysiological conditions. Much research has emerged in recent years demonstrating the involvement of HSPs and their regulator heat shock factor 1 (HSF1) in ferroptosis regulation. Understanding the machinery controlling HSF1 and HSPs in ferroptosis can be employed in developing therapeutic interventions for ferroptosis occurrence in a number of pathological conditions. Therefore, this review comprehensively summarized the basic characteristics of ferroptosis and the regulatory functions of HSF1 and HSPs in ferroptosis. Full article

Background: Amniotic fluid embolism (AFE) is one of the main causes of maternal mortality in developed countries. The most critical AFE variants may be considered from the perspective of systemic inflammation (SI), a general pathological process that includes high levels of systemic inflammatory response, neuroendocrine system distress, microthrombosis, and multiple organ dysfunction syndrome (MODS). This research work aimed to characterize the dynamics of super-acute SI using four clinical case studies of patients with critical AFE. Methods: In all the cases, we examined blood coagulation parameters, plasma levels of cortisol, troponin I, myoglobin, C-reactive protein, IL-6, IL-8, IL-10, and TNF-α, and calculated the integral scores. Results: All four patients revealed the characteristic signs of SI, including increased cytokine, myoglobin, and troponin I levels, changes in blood cortisol, and clinical manifestations of coagulopathy and MODS. At the same time, the cytokine plasma levels can be characterized not only as hypercytokinemia, and not even as a “cytokine storm”, but rather as a “cytokine catastrophe” (an increase of thousands and tens of thousands of times in proinflammatory cytokine levels). AFE pathogenesis involves rapid transition from the hyperergic shock phase, with its high levels of a systemic inflammatory response over to the hypoergic shock phase, characterized by the mismatch between low systemic inflammatory response values and the patient’s critical condition. In contrast to septic shock, in AFE there is a much more rapid succession of SI phases. Conclusion: AFE is one of the most compelling examples for studying the dynamics of super-acute SI. Full article

This study aims to investigate the effect of resveratrol on systemic inflammatory response and metabolic disorder in rats fed a high-fructose high-lipid diet (HFHLD) and exposed to round-the-clock lighting (RCL). 21 adult male Wistar rats were randomly divided into 3 groups: control (group 1, n = 7); HFHLD for 8 weeks + round-the-clock lighting (RCL) (group 2, n = 7); HFHLD + RCL + Resveratrol (in a daily dose of 5 mg/kg intragastrically (group 3, n = 7). Results show that the combined effect of HFHLD and RCL reduces the serum melatonin (p < 0.001) and accelerates pro-inflammatory activities, oxidative stress, and metabolic disorder. There is a significant increase in the serum tumour necrosis factor-alpha (TNF-α) and C-reactive protein (CRP) (both p < 0.001), blood malondialdehyde—thiobarbituric acid adducts (MDA-TBA₂) (p < 0.001), serum glucose (p < 0.01), insulin concentration, and the homeostatic model assessment insulin resistance (HOMA-IR) index (both p < 0.001), serum with very low-density lipoprotein (VLDL), and triacylglycerol (TAG) (both p < 0.001). At the same time, the decrease in the serum high-density lipoprotein (HDL) level (p < 0.001) is observed in the HFHLD + RCL group compared to the control. In the HFHLD + RCL + Resveratrol group, hypomelatonaemia (p < 0.001), pro-inflammatory actions, oxidative stress, and metabolic disorder were mitigated. Resveratrol can cause a significant rise in the serum melatonin and reduce serum TNF-α and CRP levels (both p < 0.001), blood MDA-TBA₂ (p < 0.001), serum glucose (both p < 0.01), insulin concentration, and HOMA-IR (both p < 0.001), serum VLDL and TAG (both p < 0.001) compared to the group 2, while serum HDL level increases (p < 0.01). Resveratrol attenuates pro-inflammatory responses and prevents considerable metabolic disorder in rats fed HFHLD under RCL. Full article

The prevalence of opioid use among pregnant people has been increasing over the past few decades, with a parallel increase in the rate of neonatal abstinence syndrome. Opioid agonist treatment (OAT) including methadone and buprenorphine is the recommended management method for opioid use disorders during pregnancy. Methadone has been extensively studied during pregnancy; however, buprenorphine was introduced in the early 2000s with limited data on the use of different preparations during pregnancy. Buprenorphine-naloxone has been incorporated into routine practice; however, only a few studies have investigated the use of this medication during pregnancy. To determine the safety and efficacy of this medication, we conducted a systematic review of maternal and neonatal outcomes among buprenorphine-naloxone-exposed pregnancies. The primary outcomes of interest were birth parameters, congenital anomalies, and severity of neonatal abstinence syndrome. Secondary maternal outcomes included the OAT dose and substance use at delivery. Seven studies met the inclusion criteria. Buprenorphine-naloxone doses ranged between 8 and 20 mg, and there was an associated reduction of opioid use during pregnancy. There were no significant differences in gestational age at delivery, birth parameters, or prevalence of congenital anomalies between buprenorphine-naloxone-exposed neonates and those exposed to methadone, buprenorphine monotherapy, illicit opioids, or no opioids. In studies comparing buprenorphine-naloxone to methadone, there were reduced rates of neonatal abstinence syndrome requiring pharmacotherapy. These studies demonstrate that buprenorphine-naloxone is a safe and effective opioid agonist treatment for pregnant people with OUD. Further large-scale, prospective data collection is required to confirm these findings. Patients and clinicians may be reassured about the use of buprenorphine-naloxone during pregnancy. Full article

Mongolia is located at 45° north latitude in the center of the Asian continent, and about 80% of the territory is at 1000 m above sea level. Epidemiologically, multiple sclerosis (MS) has not been investigated in Mongolia, although there have been a few MS case reports. We investigated the characteristics of MS in Mongolia for the first time, focusing on the association between MS-related parameters and depression levels. We initiated cross-sectional analyses, using data from 27 MS patients aged 20 to 60 years in Ulaanbaatar, Mongolia. The patients completed a questionnaire on their lifestyles and clinical information. We classified the MS patients on the basis of disability levels using the expanded disability status scale (EDSS) scores: 11.1% mild disability and 88.9% moderate to severe disability (median EDSS score, 5.5). We also classified the patients on the basis of depression levels using the 9-item patient health questionnaire (PHQ-9) scores: 44.4% mild depression, 40.7% moderate depression, and 14.8% severe depression (mean PHQ-9’s score, 9.96 ± 5.05). We used multivariate logistical regression analyses to identify predictors of EDSS or PHQ-9 scores. Disability levels were associated with vision and balance problems. Depression levels were associated with corticosteroid treatment; no patients were treated with disease-modifying drugs (DMDs). The odds ratios for disease onset age and treatment duration were associated with EDSS scores. In conclusion, MS onset age and treatment duration were independent predicting factors influencing the level of disability. Appropriate DMD treatment would lower the disability and depression levels. Full article

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients’ blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility. Full article