International journal of physiology, pathophysiology and pharmacology最新文献

Objectives: The significant correlation between acute myocardial infarction and subsequent hepatorenal dysfunction could result in a higher mortality rate in patients. The study aimed to evaluate the effect and mechanisms of coenzyme-Q10 (Q10) administration on hepatorenal dysfunction in an isoprenaline (ISO)-induced myocardial infarction model in rats.

Materials and methods: Twenty male rats were assigned into four groups (n = 5). Groups 1-2 were administered intraperitoneally with normal saline, groups 3-4 were pretreated with Q10 (10 mg/kg, i.p.) for 28 days, and groups 2 and 4 received ISO (200 mg/kg, i.p.) on the last two days. Body, kidney, and liver weights, antioxidants and biochemical biomarkers, and histopathological investigation of the liver and kidney tissues were performed.

Results: The administration of ISO significantly (P < 0.05) increased oxidative stress and altered the liver and renal function integrity and morphology. Pretreatment with Q10 demonstrated a protective effect against biochemical and histological alterations through significantly enhanced antioxidant actions, notably increasing the levels of superoxide dismutase, catalase, glutathione, and glutathione transferase; reduced liver enzymes (aspartate transaminase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase), decreased urea and creatinine concentrations and reduced the gravity of histomorphological changes in hepatic and renal tissues of ISO treated rats.

Conclusion: Overall, our result suggests that Q10 confers hepatic and renal protection against ISO-induced hepatorenal dysfunction accompanying myocardial infarction through its antioxidant effects and amelioration of fibrotic changes.

Objective: The Heat Shock Protein 70 (HSP70) family is a highly conserved group of molecular chaperones essential for maintaining cellular homeostasis. These proteins are necessary for protein folding, assembly, and degradation and involve cell recovery from stress conditions. HSP70 proteins are upregulated in response to heat shock, oxidative stress, and pathogenic infections. Their primary role is preventing protein aggregation, refolding misfolded proteins, and targeted degradation of irreparably damaged proteins. Given their involvement in fundamental cellular processes and stress responses, HSP70 proteins are critical for cell survival and modulating disease outcomes in cancer, neurodegeneration, and other pathologies. The present study aims to understand domain architecture, physicochemical properties, phosphorylation, ubiquitination, and alternative polyadenylation site prediction in various HSP70 members.

Method: SMART and InterProScan software were used for domain analysis. EXPASY Protparam, NetPhos 3.1 server DTU, and MUbisiDa were used for physicochemical analysis, phosphorylation, and ubiquitination site analysis, respectively. Alternative polyadenylation was studied using the EST database.

Result: Domain analysis shows that coiled-coil and nucleotide-binding domains are present in some of the HSP70 members. Five HSP70 family members have alternate polyadenylation sites in their 3'UTR.

Conclusion: The present work has provided valuable insights into their structure, functions, interactome, and polyadenylation patterns. Studying their therapeutic potential in diseases like cancer can be helpful.

Metabolic syndrome is a group of pathological disorders increasing the risk of serious diseases including cardiovascular disease, stroke, type 2 diabetes. Global widespread of the metabolic syndrome has put a heavy social burden. Interestingly, a crucial link between the metabolic syndrome and a psychiatric disorder may frequently coexist, in which certain shared mechanisms might play a role for the pathogenesis. In fact, some microRNAs (miRNAs) have been detected in the overlap pathology, suggesting a common molecular mechanism for the development of both disorders. Subsequent studies have revealed that these miRNAs and several metabolites of gut microbiota such as short chain fatty acids (SCFAs) might be involved in the development of both disorders, in which the association between gut and brain might play key roles with engram memory for the modulation of immune cells. Additionally, the correlation between brain and immunity might also influence the development of several diseases/disorders including metabolic syndrome. Brain could possess several inflammatory responses as an information of pathological images termed engrams. In other words, preservation of the engram memory might be achieved by a meta-plasticity mechanism that shapes the alteration of neuron linkages for the development of immune-related diseases. Therefore, it might be rational that metabolic syndrome and psychiatric disorders may belong to a group of immune-related diseases. Disrupting in gut microbiota may threaten the body homeostasis, leading to initiate a cascade of health problems. This concept may contribute to the development of superior therapeutic application with the usage of some functional components in food against metabolic and psychiatric disorders. This paper reviews advances in understanding the regulatory mechanisms of miRNAs with the impact to gut, liver and brain, deliberating the probable therapeutic techniques against these disorders.

Alzheimer's disease is the most general type of cognitive impairments. Until recently, strategies that prevent its clinical progression have remained more elusive. Consequently, research direction should be for finding effective neuroprotective agents. It has been suggested oxidative stress, mitochondrial injury, and inflammation level might lead to brain cell death in many neurological disorders. Therefore, several autophagy-targeted bioactive compounds may be promising candidate therapeutics for the prevention of brain cell damage. Interestingly, some risk genes to Alzheimer's disease are expressed within brain cells, which may be linked to cholesterol metabolism, lipid transport, endocytosis, exocytosis and/or caveolae formation, suggesting that caveolae may be a fruitful therapeutic target to improve cognitive impairments. This review would highlight the latest advances in therapeutic technologies to improve the treatment of Alzheimer's disease. In particular, a paradigm that serotonin and N-methyl-d-aspartate (NMDA) receptors agonist/antagonist within caveolae structure might possibly improve the cognitive impairment. Consequently, cellular membrane biophysics should improve our understanding of the pathology of the cognitive dysfunction associated with Alzheimer's disease. Here, this research direction for the purpose of therapy may open the potential to move a clinical care toward disease-modifying treatment strategies with certain benefits for patients.

Extracellular vesicles (EVs) have emerged as a fascinating area of research in molecular biology, with diverse therapeutic applications. These small membrane-bound structures, released by cells into the extracellular space, play a crucial role in intercellular communication and hold great potential for advancing medical treatments. The aim of this study is to have a narrative review on the use and therapeutic applications of EVs. Their unique characteristics, including stability, biocompatibility, and the ability to traverse biological barriers, make them promising tools for targeted drug delivery. By engineering EVs to encapsulate specific cargo molecules, such as therapeutic proteins, small interfering RNA (siRNA), or anti-cancer drugs, researchers can enhance drug stability and improve targeted delivery to desired cells or tissues. This approach can minimize off-target effects and improve therapeutic efficacy. Based on our literature search, we found that EVs can be used as biomarkers to predict diseases. Although much progress has been made in understanding the biology and function of exosomes, there are still unanswered questions that require further research. This includes identifying appropriate and safe techniques for producing exosomes in large quantities, determining which types of cells are suitable for exosome donor cells for therapeutic purposes, and investigating the safety of exosomes in human studies. Overall, the use of exosomes in clinical therapeutic applications requires a strong understanding of molecular signaling cascades and exosome profiles, as well as the specificity and sensitivity of biomarker and drug delivery methods.

Background: PET/CT and PET/MRI are two useful imaging modalities in neuro-oncology. Our aim was to review the existing literature on the benefits and drawbacks of using PET/CT and PET/MRI in the diagnosis of central nervous system (CNS) tumors.

Methods: A literature search was conducted using valid databases, limited to English-language articles published between 2010 and 2023, and independently reviewed by two reviewers. A standard data extraction form was used to extract data from the included papers. The results were condensed and narratively presented, accompanied by supporting data from the included investigations.

Results: The study analyzed 28 articles, mostly from Europe. The results varied, with some studies comparing PET/CT and PET/MRI, examining specific types of brain tumors, pediatric tumors, or focusing on specific PET/CT or PET/MRI modalities. The synthesis aimed to provide a comprehensive overview of PET/CT and PET/MRI use in CNS malignancies.

Conclusions: PET/MRI offers promising advantages in neuro-oncology diagnosis and follow-up imaging, but its use should be prioritized in appropriate situations.

Background: Granule cells in the hippocampus project axons to hippocampal CA3 pyramidal cells where they form large mossy fiber terminals. We have reported that these terminals contain the gap junction protein connexin36 (Cx36) specifically in the stratum lucidum of rat ventral hippocampus, thus creating morphologically mixed synapses that have the potential for dual chemical/electrical transmission.

Methodology: Here, we used various approaches to characterize molecular and electrophysiological relationships between the Cx36-containing gap junctions at mossy fiber terminals and their postsynaptic elements and to examine molecular relationships at mixed synapses in the brainstem.

Results: In rat and human ventral hippocampus, many of these terminals, identified by their selective expression of vesicular zinc transporter-3 (ZnT3), displayed multiple, immunofluorescent Cx36-puncta representing gap junctions, which were absent at mossy fiber terminals in the dorsal hippocampus. In rat, these were found in close proximity to the protein constituents of adherens junctions (i.e., N-cadherin and nectin-1) that are structural hallmarks of mossy fiber terminals, linking these terminals to the dendritic shafts of CA3 pyramidal cells, thus indicating the loci of gap junctions at these contacts. Cx36-puncta were also associated with adherens junctions at mixed synapses in the brainstem, supporting emerging views of the structural organization of the adherens junction-neuronal gap junction complex. Electrophysiologically induced long-term potentiation (LTP) of field responses evoked by mossy fiber stimulation was greater in the ventral than dorsal hippocampus.

Conclusions: The electrical component of transmission at mossy fiber terminals may contribute to enhanced LTP responses in the ventral hippocampus.

Background: Sexually dimorphic spinal motoneurons (MNs) in the dorsomedial nucleus (DMN) and dorsolateral nucleus (DLN) as well as those in the cremaster nucleus are involved in reproductive behaviours, and the cremaster nucleus additionally contributes to testicular thermoregulation. It has been reported that MNs in DMN and DLN are extensively linked by gap junctions forming electrical synapses composed of connexin36 (Cx36) and there is evidence that subpopulation of MNs in the cremaster nucleus are also electrically coupled by these synapses.

Methodology: We used immunofluorescence methods to detect enhanced green fluorescent protein (eGFP) reporter for Cx36 expression in these motor nuclei.

Results: We document in male mice that about half the MNs in each of DMN and DLN express eGFP, while the remaining half do not. Further, we found that the eGFP⁺ vs. eGFP^- subsets of MNs in each of these motor nuclei innervate different target muscles; eGFP⁺ MNs in DMN and DLN project to sexually dimorphic bulbocavernosus and ischiocavernosus muscles, while the eGFP^- subsets project to sexually non-dimorphic anal and external urethral sphincter muscles. Similarly, eGFP⁺ vs. eGFP^- cremaster MNs were found to project to anatomically distinct portions of the cremaster muscle. By immunofluorescence, nearly all motoneurons in both DMN and DLN displayed punctate labelling for Cx36, including at eGFP⁺/eGFP⁺, eGFP⁺/eGFP^- and eGFP^-/eGFP^- cell appositions.

Conclusions: Most if not all motoneurons in DMN and DLN are electrically coupled, including sexually dimorphic and non-dimorphic motoneurons with each other, despite absence of eGFP reporter in the non-dimorphic populations in these nuclei that have selective projections to sexually non-dimorphic target muscles.

The everyday clinical practice of anesthesia has been transformed by the new reversal agent Sugammadex. With multiple benefits to this agent, including immediate reversibility of certain neuromuscular blocking agents, a more robust reversal, and the ability to keep a deeper plane of paralysis throughout surgical procedures, this medication has provided anesthesiologists with a new and improved ability to provide high quality care to their patients. The effectiveness of the reversal provided by this agent has also improved the incidence of post-operative complications relating to improper reversal and the need for reintubations. With the new American Society of Anesthesiologists (ASA) guidelines on neuromuscular blockade and its reversal, Sugammadex has been easily and quickly adopted into everyday clinical practice.

Introduction: Metabolic acidosis is very common amongst critically ill sepsis patients partly due to the presence of unmeasured ions in serum. These ions can be detected by anion gap (AG) or strong ion gap (SIG) concentration values. The purpose of this study is to assess the correlation and potential agreement of the two methods in critically ill patients with sepsis.

Materials and methods: The present is a retrospective study including septic patients admitted to the Intensive Care Unit from December 2014 to July 2016. The [SIG] and the [AG] corrected for albumin and lactate ([AG_cl]) were calculated on admission and on sepsis remission or deterioration. The correlation of the two parameters was assessed in all patient groups using the Pearson correlation coefficient and linear regression analysis and the agreement with Bland-Altman plots. ROC survival curves were also generated for the patients in relation to the values of [AG_cl], [SIG] and inorganic [SIG] ([SIG_i]) on admission.

Results: There was a strong correlation linking [AG_cl] and [SIG] values (r>0.9, P<0.05) in all patient groups. The results from all three linear regression equations were statistically significant as the models predicted the [AG_cl] value from the [SIG] value with high accuracy. The mean difference of the two methods (i.e. [AG_cl] - [SIG] in every patient separately) in septic patients on admission was 11.75 mEq/l with 95% limits of agreement [9.7-13.8]; in patients with sepsis deterioration, it was 11.8 mEq/l with 95% limits of agreement [9.8-13.7] and in patients with sepsis remission, it was 11.5 mEq/l with 95% limits of agreement [10.4-12.7]. ROC survival curves demonstrated a small area under the curve (AUC): [SIG] AUC: 0.479, 95% CI [0.351, 0.606], [SIG_i] AUC: 0.581, 95% CI [0.457, 0.705], [AG_cl] AUC: 0.529, 95% CI [0.401, 0.656].

Conclusion: [AG_cl] and [SIG] demonstrate excellent correlation in septic patients, with a mean difference of about 12 mEq/l. Both parameters failed to demonstrate any predictive ability regarding patient mortality.