International journal of physiology, pathophysiology and pharmacology最新文献

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.

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.