Biomedicines最新文献

Chronic kidney disease (CKD) is characterized by a progressive and usually irreversible deterioration of renal function [...].

The epiligament (EL), described in 1990 as a connective tissue layer distinguishable from the ligament proper, has only recently gained recognition for its critical role in ligament function and repair. Previously overlooked, the EL is now understood to be a dynamic structure, particularly in the context of medial collateral ligament (MCL) healing. Rat model studies demonstrate that the EL actively contributes to ligament repair by serving as a source of cells and blood vessels, findings later corroborated in human studies. The EL's role in spontaneous MCL healing highlights its importance, raising the question of whether differences in EL morphology and activity contribute to the poor healing capacity of the anterior cruciate ligament (ACL). Comparative studies reveal significant disparities in EL cellularity and activity between the ACL and MCL. The EL of the MCL is hypercellular, with robust expression markers like α-smooth muscle actin (α-SMA) and collagen types III and V, essential for tissue remodeling and structural integrity. Conversely, the ACL's EL is less vascularized and exhibits weaker expression of these markers. While vascular endothelial growth factor (VEGF) promotes angiogenesis, its effectiveness is limited in the ACL due to restricted vascularization. Similarly, CD34, a progenitor cell marker, is more prominently expressed in the MCL's EL, further supporting its superior healing potential. These findings suggest that the EL's distinct structural and functional attributes are key determinants of ligament healing. Targeting the EL's regenerative properties offers a promising therapeutic strategy, particularly for improving ACL repair outcomes. Further research is necessary to validate and expand these findings.

Introduction: The classification of antiphospholipid syndrome (APS) comprises clinical criteria (vascular thrombosis or obstetric complications throughout life) and laboratory criteria (antiphospholipid antibodies (aPLs) positivity, confirmed at least twice at 12-week interval). Methods: In 100 patients admitted to the hospital with COVID-19 pneumonia, thrombosis and pregnancy complications were recorded during the hospital stay and in personal medical history. They were tested for nine types of aPLs at four time points (admission, deterioration, discharge, and 3-month follow-up): anticardiolipin (aCL), anti-β2-glycoproteinI (anti-β2GPI), and antiphosphatidylserine/prothrombin (aPS/PT) isotypes IgM/IgG/IgA. Results: During hospitalization, aPLs were detected at least once in 51% of patients. All 7% of deceased patients tested negative for aPLs upon admission, and only one patient became aCL IgG positive as his condition worsened. In 83.3% of patients, intrahospital thrombosis was not related to aPLs. One patient with pulmonary artery and cerebral artery thrombosis was given an APS diagnosis (triple aPLs positivity on admission, double on follow-up). Personal anamnesis (PA) for thromboembolism was verified in 10 patients, all of whom tested negative for aPLs at admission; however, transition to aPLs positivity at discharge (as the disease subsided) was seen in 60% of patients: three of six with arterial thrombosis (at follow-up, two did not appear, and one was negativized) and three of four with deep vein thrombosis (one was confirmed at follow-up and diagnosed with APS, one was negativized, and one did not appear). At admission, the majority of the aPLs were of the aCL IgG class (58.8%). Unexpectedly, as the COVID-19 disease decreased, anti-β2GPI IgG antibodies (linked with thromboses) became newly positive at discharge (14.9%), as confirmed at follow-up (20.8%). Conclusion: The incidence of APS in our cohort was 2.0%, whereas in the general population, it ranges from 0.001% to 0.002%. The incidence might have increased even more if the four aPLs-positive patients with intrahospital thrombosis/history of thrombosis had attended follow-up. Recommendation: All patients with severe COVID-19 or post-COVID syndrome should be evaluated for current/previous thrombosis and tested for aPLs at least twice: at admission to the hospital and at discharge, then retested 3 months later in positive cases in order to be given the appropriate therapy.

Achilles tendon injuries are extremely common and have a significant impact on the physical and mental health of individuals. Both conservative and surgical treatments have unsatisfactory results. The search for new therapeutic tools, using cell therapies with stem cells (SC) and biological tissues, such as amniotic membranes (AM), has proved useful for the regeneration of injured tendons. Background/Objectives: This research was carried out to assess the capacity of tissue repair in animal models of Achilles tendinopathy, in which rats were submitted to complete sections of the tendon, and the effects of using bone marrow SC and/or AM graft are evaluated. Methods: Thirty-seven Wistar rats, submitted to complete surgical section of the Achilles tendon and subsequent tenorrhaphy, were randomized into four groups: Control Group (CG), received saline solution; SC Group (SCG) received an injection of SC infiltrated directly into the tendon; AM Group (AMG), the tendon was covered with an AM graft; SC + AM Group (SC+AMG), has been treated with an AM graft and SC local injection. Six weeks later, the Achilles tendons were evaluated using a histological score and immunohistochemical pro-healing markers such as Interferon-γ, AKT, and mTOR. Results: There were no differences between morphometric histological when evaluating the Achilles tendons of the samples. No significant differences were found regarding the expression of AKT-2 and mTOR markers between the study groups. The main finding was the presence of a higher concentration of Interferon-γ in the group treated with SC and AM. Conclusions: The isolated use of SC, AM, or the combination of SC-AM did not produce significant changes in tendon healing when the histological score was evaluated. Similarly, no difference was observed in the expression of AKT-2 and mTOR markers. An increase in the expression of Interferon-γ was observed in SC+AMG. This suggests that such therapies may be potentially beneficial for the regeneration of injured tendons. However, as tendon repair mechanisms are very complex, further studies should be carried out to verify the benefits of the tendon structure and function.

Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent hereditary disorder characterized by distinct phenotypic variability that has posed challenges for advancing in-depth research. Recent advancements in kidney organoid construction technologies have enabled researchers to simulate kidney development and create simplified in vitro experimental environments, allowing for more direct observation of how genetic mutations drive pathological phenotypes and disrupt physiological functions. Emerging technologies, such as microfluidic bioreactor culture systems and single-cell transcriptomics, have further supported the development of complex ADPKD organoids, offering robust models for exploring disease mechanisms and facilitating drug discovery. Nevertheless, significant challenges remain in constructing more accurate ADPKD disease models. This review will summarize recent advances in ADPKD organoid construction, focusing on the limitations of the current techniques and the critical issues that need to be addressed for future breakthroughs. New and Noteworthy: This review presents recent advancements in ADPKD organoid construction, particularly iPSC-derived models, offering new insights into disease mechanisms and drug discovery. It focuses on challenges such as limited vascularization and maturity, proposing potential solutions through emerging technologies. The ongoing optimization of ADPKD organoid models is expected to enhance understanding of the disease and drive breakthroughs in disease mechanisms and targeted therapy development.

The renal resistive index (RRI), a Doppler ultrasound-derived parameter measuring renal vascular resistance, has emerged as a promising non-invasive tool to evaluate renal hemodynamics in critically ill patients, particularly those with acute respiratory distress syndrome (ARDS) and heart failure (HF). This narrative review examines the current evidence for RRI measurement in these conditions, exploring its physiological bases, methodology, clinical applications, and limitations. In ARDS, RRI reflects the complex interactions between positive pressure ventilation, hypoxemia, and systemic inflammation, showing a role in predicting acute kidney injury and monitoring response to interventions. In HF, RRI is able to assess venous congestion and cardiorenal interactions and can also serve as a prognostic indicator. Many studies have shown RRI's superiority or complementarity to traditional biomarkers in predicting renal dysfunction, although its interpretation requires consideration of multiple patient-related factors. Key challenges include operator dependency, lack of standardization, and complex interpretation in multi-organ dysfunction. Future research should focus on measurement standardization, development of automated techniques, investigation of novel applications like intraparenchymal renal resistive index variation, and validation of RRI-guided management strategies. Despite its limitations, RRI represents a valuable tool that offers bedside and real-time insights into renal hemodynamics and potential guidance for therapeutic interventions. Further research is needed to fully clarify its clinical potential and address current limitations, particularly in critical care settings involving multiple organ dysfunction.

Background/Objectives: Epithelial-Mesenchymal Transition (EMT) is the process by which epithelial cells acquire mesenchymal properties, which helps endometriotic cells migrate and invade. This study looks at the expression of E-CADHERIN, a critical epithelial marker, and miR-200b, an EMT regulator, in several types of endometriosis, including endometriomas and deep infiltrating endometriotic (DIE) nodules. Methods: We examined 19 individuals with endometriosis (9 with just endometriotic cysts and 10 with both DIE and endometriotic cysts) and 8 controls with benign gynecological abnormalities. Tissue samples were taken during laparoscopic surgery, and E-CADHERIN and miR-200b expression were measured using Real-Time PCR, with G6PD and U6 as controls. Results:E-CADHERIN expression was maintained in the eutopic endometrium of both ovarian and DIE types, but it was considerably reduced in endometriotic cysts, indicating heightened mesenchymal features. miR-200b was downregulated in the eutopic endometrium of ovarian endometriosis but upregulated in DIE. Endometriotic cysts in both groups had greater miR-200b expression than their corresponding eutopic endometrium. E-CADHERIN and miR-200b expression in DIE lesions was similar to that found in matched eutopic endometrium. Conclusions: The regulation of E-CADHERIN and miR-200b varies across ovarian and DIE lesions. The miR-200b-ZEB1 feedback loop is increased in DIE eutopic endometrium but downregulated in ovarian endometriosis. E-CADHERIN downregulation in endometriotic cysts indicates heightened mesenchymal dynamics, whereas DIE nodules have gene expression patterns similar to eutopic endometrium. These findings emphasize the distinct regulatory processes that govern endometriotic lesions.

Radiotherapy (RT) is one of the major cornerstones in managing gastrointestinal (GI) cancers. However, several side effects, such as intestinal inflammation, mucosal injury, and dysbiosis, often compromise this. The gut microbiota increasingly attracts much interest as an essential modulator of RT effects influencing immune responses and tissue repair. Through short-chain fatty acids such as butyrate, representatives of certain bacterial species play a crucial role under normal conditions, keeping the mucosal integrity intact and reducing oxidative stress-mediated damage. Dysbiosis, a state where diminished microbial diversity and increased pathogenic species in the microbiota are seen, amplifies RT-induced toxicity in patients. Clinical investigations highlight that microbiota-targeted interventions, including probiotics, prebiotics, and fecal microbiota transplantation, hold the means to augment RT efficacy and lessen toxicity. Increased microflora diversity and specific microbial profiles have yielded serious patient improvements. Advanced RT methods use stereotactic body radiotherapy combined with microbiota modulation as a promising technique to shield healthy tissue and maximize immune-mediated antitumor effects. Additionally, there is an implication in tumor behavior regulated by the intratumoral microbiota regarding the response to radiotherapy. Notably, the modulation of gut and tumor microbiota provides an avenue to optimize RT benefits in GI cancers, underscoring the importance of personalized therapy.

Background: The pathogenesis of psoriasis is poorly understood. Increased reactive oxygen species (ROS) and lipid peroxidation are crucial in the inflammatory processes, including psoriasis. Thus, microelements, such as zinc and copper, may play a significant role in this disease's development. Methods: Due to the paucity and inconsistency of literature data, we studied the levels of copper and zinc in blood and serum from 301 unselected psoriatic patients and 301 matched healthy controls and examined any associations among the microelements and clinical course or SOD2 (rs4880), CAT (rs1001179), GPX1 (rs1050450), and DMGDH (rs921943) DNA variants. Results: The mean blood copper levels were 864.94 µg/L and 907.24 µg/L, respectively, for controls and psoriasis patients (p < 0.001). The mean serum copper levels were 1,104.14 µg/L and 1191.72 µg/L, respectively, for controls and psoriasis patients (p < 0.001). The psoriasis risk was highest the among participants with the highest blood levels (>950.02 µg/L, OR: 2.36; 95% CI: 1.31-4.26; p = 0.004) and the highest serum concentrations (>1276.98 µg/L, OR: 3.08; 95% CI: 1.77-5.36; p < 0.001). The mean serum zinc levels were significantly lower (p < 0.001) among patients (910.87 µg/L) when compared to controls (979.68 µg/L). The mean blood zinc levels were not significantly different in cases and controls. Subjects with the lowest serum zinc levels (<843.68 µg/L) were affected more frequently (OR: 3.85; 95% CI: 2.24-6.60; p < 0.001). We found positive correlations between copper levels and PASI and inverse correlations of serum zinc levels with PASI and NAPSI scores. There were no associations between the levels of microelements and studied DNA variants. Conclusions: Our results support the thesis of an association between psoriasis onset and altered course of the disease with upset levels of copper and zinc. Future prospective studies might focus on optimization of the concentration of these trace elements for prophylaxis and to support the treatment of psoriasis.

Background/Objectives: Chronic wounds pose a significant health concern, with their prevalence increasing due to various etiologies. The global aging population further contributes to this rise, placing a substantial burden on healthcare systems in developed countries. This work aimed to develop new therapeutic options in the form of creams and dressings based on honey, gellan gum, and hyaluronic acid for preventing and treating chronic wounds across all stages. Methods: To address this, after the formulations were developed, in vitro cytocompatibility was determined. To confirm biocompatibility, an ovine wound model was used: full-thickness excisional wounds were treated with three formulations, namely gellan gum and honey sponges (GG-HNY), gellan gum, honey and hyaluronic acid sponges (GG-HA-HNY) and a honey-based cream (cream FB002). Daily assessments, including visual evaluation and wound scoring, were conducted for 30 days. Following the study period, tissues were collected for histological analyses. Results: The macroscopic examination revealed that all therapeutic groups facilitated lesion closure. Lesion size reduction, granulation tissue disappearance, and scar tissue development were consistent across all groups, with the group receiving cream demonstrating an advanced stage of healing. All groups achieved substantial wound closure by day 30, with no significant differences. Histopathological analysis following ISO standards revealed that GG-HA-HNY had the lowest ISO score, indicating minimal reactivity and inflammation, which corroborated the cytocompatibility. Conclusions: Combining these insights with previous findings enhances our understanding of wound regeneration dynamics and contributes to refining therapeutic strategies for chronic wounds. The formulations were designed to balance therapeutic efficacy with cost-effectiveness, leveraging low-cost raw materials and straightforward production methods.