Tissue Pathology Research Articles

Osteoarticular tuberculosis: imaging findings in pediatric patients.

Osteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB that has the potential to damage joints and bones, generating long-term impairment. Mainly, the initial diagnosis of osteoarticular TB relies on clinical findings and imaging. When required, imaging can aim for less invasive tissue or fluid sampling for pathology, microbiology, and molecular biology analysis. Most TB diagnosis tests have variable and frequently poor sensitivities; however, bone biopsy samples have demonstrated a high percentage of culture positivity. Clinical and imaging findings of osteoarticular TB often mimic other processes, such as rheumatoid arthritis or chronic recurrent multifocal osteomyelitis. When the infection affects the growth plates, angular deformities and extremity length discrepancies can arise. Unfortunately, several osteoarticular TB cases are detected late due to the nonspecific nature of clinical symptoms and non-characteristic imaging findings. This article reviews the most common and atypical osteoarticular TB imaging presentations to increase awareness of osteoarticular TB.

Subchondral Bone Degeneration and Pathology 3-15 Years Following Ankle Sprain Injury in Adolescent Sport.

Sport-related ankle sprains (SASs) are prevalent in adolescents (ages 10-19), increasing the risk of developing posttraumatic osteoarthritis (PTOA). Although early ankle osteoarthritis (OA) is not well defined, OA eventually includes alterations in bone mineral density (BMD), structural changes, and soft tissue pathology. This study examined the impact of SAS sustained in adolescent sport on bone and soft tissue structural outcomes 3-15 years postinjury. Participants (n = 10) with prior unilateral SAS in adolescent sport (HxAI) were compared to age- and sex-matched controls. To assess injury-related pathologies and BMD, 1.5-tesla (T) extremity magnetic resonance imaging (MRI) and computed tomography scans were used. Semiquantitative scores for injury patterns and OA features from MRI scans were summed and compared between groups. The talus, calcaneus, navicular, and 5% distal tibia were segmented, and BMD was measured for each bone. All HxAI participants exhibited MRI injury pathology (median 2; IQR 1-6), whereas only 1 of 10 controls showed pathology (median 0; IQR 0-0), χ2(1, n = 20) = 16.36, P < .001. Both the injured and uninjured ankles in HxAI displayed injury pattern pathology. Additionally, 3 of 10 injured ankles and 2 of 10 uninjured ankles in the HxAI group (median 0; IQR 0-3), but none of the controls (median 0; IQR 0-0), exhibited OA features. In the HxAI group, talus BMD was lower in the injured ankle (502.4 ± 67.9 g/cm3) compared with the uninjured ankle (515.6 ± 70.1 g/cm3) (F = 13.33, P = .002), with no significant BMD differences at the calcaneus, navicular, or 5% distal tibia. No differences were observed between the ankles of the control group. The presence of injury pattern pathology, structural changes, and reduced talus BMD suggest that degenerative changes may occur in individuals as early as 3-15 years following ankle injury.

Abstract B007: Unlocking antiviral immunity against endogenous retroviruses in skin squamous cell carcinomas

Abstract Known as molecular parasites that invaded our genome through ancestors, transposons (mainly retrotransposons) are interspersed genomic repeats that constitute ∼40% of the mammalian genome. Primarily residing in the heterochromatin, retrotransposons exhibit dynamic expressions to orchestrate embryonic development and shape adult functions. Although rare, a cohort of evolutionarily young retrotransposons resisted extinction, whose selfish activities underlie polymorphic variations and genetic diseases including cancer. While the extraordinary molecular and functional heterogeneity of retrotransposons has been long recognized, mechanistic dissection remains challenging. To tackle this challenge, we use murine skin as our model, given its well-characterized, abundant, and highly accessible adult stem cells, not only mediating postnatal remodeling and tissue repair, but also serving as cell of origin for squamous cell carcinomas. By analyzing a genetic model lacking a known retrotransposon suppressor, histone methyltransferase Setdb1, which we found to be essential in the adult skin, we saw hair loss and hair follicle stem cell exhaustion phenotype, accompanied by a robust and selective surge of endogenous retroviruses (ERVs). When combined with squamous cell carcinoma drivers, Setdb1 loss significantly blocked tumor progression in vivo. We detected abundant retroviral peptides originated from its full-length copies through mass spectrometry and viral-like particles through transmission electron microscopy that are immunoreactive to previously reported ERV surface envelope (env) antibody. Similar viral-like particles were broadly evident across several epithelial tissues beyond skin, implicating its conserved function across squamous cancers. Mechanistically, epithelial originated ERVs elicit tissue wide inflammatory response, and can be ameliorated by pharmacological or genetic inhibition of retroviral activity. Moreover, ERV reactivation induced replication stress functionally accounts for stem cell exhaustion, therefore serving as a specific therapeutic vulnerability in squamous cancers. As an evolutionary conundrum, viral-coding ERVs pose a threat to host fitness and yet, they’ve resisted extinction persisting in the mammalian genome. Our findings suggest ERVs wrestle with the host surveillance programs to regulate adult tissue physiology and pathology, thus providing a key target in eliciting innate immunity in squamous cell carcinomas. Citation Format: Ying Lyu, Yejing Ge. Unlocking antiviral immunity against endogenous retroviruses in skin squamous cell carcinomas [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RNAs as Drivers, Targets, and Therapeutics in Cancer; 2024 Nov 14-17; Bellevue, Washington. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(11_Suppl):Abstract nr B007.

Value of [68Ga]Ga-NYM046 PET/CT, in Comparison with 18F-FDG PET/CT, for Diagnosis of Clear Cell Renal Cell Carcinoma.

This study aimed to investigate the diagnostic efficacy of [68Ga]Ga-NYM046 PET/CT in animal models and patients with clear cell renal cell carcinoma (ccRCC) and to compare its performance with that of 18F-FDG PET/CT. Methods: The invivo biodistribution of [68Ga]Ga-NYM046 was evaluated in mice bearing OS-RC-2 xenografts. Twelve patients with ccRCC were included in the study; all completed paired [68Ga]Ga-NYM046 PET/CT and 18F-FDG PET/CT. The diagnostic efficacies of these 2 PET tracers were compared. Moreover, the positive rate of carbonic anhydrase IX in the pathologic tissue sections was compared with the SUVmax obtained by PET/CT. Results: The tumor accumulation of [68Ga]Ga-NYM046 at 1 h after injection in OS-RC-2 xenograft tumor models was 7.21 ± 2.39 injected dose per gram of tissue. Apart from tumors, the kidney and stomach showed high-uptake distributions. In total, 9 primary tumors, 96 involved lymph nodes, and 147 distant metastases in 12 patients were evaluated using [68Ga]Ga-NYM046 and 18F-FDG PET/CT. Compared with 18F-FDG PET/CT, [68Ga]Ga-NYM046 PET/CT detected more primary tumors (9 vs. 1), involved lymph nodes (95 vs. 92), and distant metastases (137 vs. 127). In quantitative analysis, the primary tumors' SUVmax (median, 13.5 vs. 2.4; z = -2.668, P = 0.008) was significantly higher in [68Ga]Ga-NYM046 PET/CT. Conversely, the involved lymph nodes' SUVmax (median, 5.9 vs. 7.6; z = -3.236, P = 0.001) was higher in 18F-FDG PET/CT. No significant differences were found for distant metastases (median SUVmax, 5.0 vs. 5.0; z = -0.381, P = 0.703). Higher [68Ga]Ga-NYM046 uptake in primary tumors corresponded to higher expression of carbonic anhydrase IX, with an R 2 value of 0.8274. Conclusion: [68Ga]Ga-NYM046 PET/CT offers a viable strategy for detecting primary tumors, involved lymph nodes, and distant metastases in patients with ccRCC.

Hyperspectral imaging in neurosurgery: a review of systems, computational methods, and clinical applications.

Accurate identification between pathologic (e.g., tumors) and healthy brain tissue is a critical need in neurosurgery. However, conventional surgical adjuncts have significant limitations toward achieving this goal (e.g., image guidance based on pre-operative imaging becomes inaccurate up to 3cm as surgery proceeds). Hyperspectral imaging (HSI) has emerged as a potential powerful surgical adjunct to enable surgeons to accurately distinguish pathologic from normal tissues. We review HSI techniques in neurosurgery; categorize, explain, and summarize their technical and clinical details; and present some promising directions for future work. We performed a literature search on HSI methods in neurosurgery focusing on their hardware and implementation details; classification, estimation, and band selection methods; publicly available labeled and unlabeled data; image processing and augmented reality visualization systems; and clinical study conclusions. We present a detailed review of HSI results in neurosurgery with a discussion of over 25 imaging systems, 45 clinical studies, and 60 computational methods. We first provide a short overview of HSI and the main branches of neurosurgery. Then, we describe in detail the imaging systems, computational methods, and clinical results for HSI using reflectance or fluorescence. Clinical implementations of HSI yield promising results in estimating perfusion and mapping brain function, classifying tumors and healthy tissues (e.g., in fluorescence-guided tumor surgery, detecting infiltrating margins not visible with conventional systems), and detecting epileptogenic regions. Finally, we discuss the advantages and disadvantages of HSI approaches and interesting research directions as a means to encourage future development. We describe a number of HSI applications across every major branch of neurosurgery. We believe these results demonstrate the potential of HSI as a powerful neurosurgical adjunct as more work continues to enable rapid acquisition with smaller footprints, greater spectral and spatial resolutions, and improved detection.

Histologic and immunohistochemical analysis of connective tissue changes in patients with intestinal sutures failure

Objective. To determine the role of connective tissue pathology in the development of intestinal suture failure in order to improve the results of treatment of patients with this complication. Materials and methods. The study included 45 patients with intestinal suture failure who were treated at the Shalimov National Research Center for Surgery and Transplantation of the National Academy of Medical Sciences of Ukraine in 2017–2023. Results. A comprehensive study of fragments of small and large intestine tissues revealed similar morphological changes in patients with phenotypic signs of undifferentiated connective tissue dysplasia and intestinal sutures failure. Immunohistochemical examination of tissues with monoclonal antibodies to α–smooth muscle actin in both groups of patients revealed uneven, focal expression in smooth muscle differentiation cells and fibroblasts; with monoclonal antibodies to type IV collagen – moderate positive expression in the basal membrane of blood vessels, in smooth muscle cells of the muscle layer of the vessel wall, in areas of connective tissue, which meant pathological remodeling of connective tissue. Conclusions. The similar results of histological and immunohistochemical studies in patients with signs of undifferentiated connective tissue dysplasia and intestinal sutures failure confirm the influence of connective tissue pathology on the development of this complication.

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome.

Bardet-Biedl syndrome (BBS) is a rare autosomal-recessive ciliopathy with pathogenic variants in 26 BBS genes. It affects multiple organs, including the kidney and liver, with varying degrees regarding extent and time of first manifestation. Structural renal anomalies are an early feature and end-stage kidney disease (ESKD) cumulates to 25% in adulthood. Early-onset hyperphagia-associated obesity is another major symptom and contributes to liver pathology, presenting as steatosis/fibrosis. Aim of this study is the evaluation of high-end ultrasound (US) technologies in BBS patients regarding their potential to discriminate liver and kidney tissue pathology at an early stage. Patients with genetically proven BBS were recruited from the University Children's Hospital of Essen and from BBS patient days hosted in Germany. Acute illness was an exclusion criterion. Clinical and laboratory data were extracted from patients' digital records or medical letters. High-resolution ultrasound (US) imaging was utilized, including attenuation imaging (ATI), shear wave elastography (SWE) and dispersion (SWD) of liver tissue. 49 BBS patients (24/49 male; 1.1-51.0years, mean 17.8years) were included in the study. Mean body weight (SDS 2.13 ± 1.33) and BMI (SDS 2.64 ± 1.18) were increased. Structural kidney abnormalities (dysplasia, cysts) were present in 75% (36/48), and persistent fetal lobulation in 44% (21/48). Renal function was impaired in 27% (13/49) of whom 3 had ESKD (kidney transplantation (n = 2), hemodialysis (n = 1)). Elevation of liver enzymes was detected in 38% (16/42). In 51% (25/49) ATI of liver tissue was increased, indicating hepatic steatosis, and correlated with BMI SDS, liver size, and enzymes. SWE was elevated in 61% (30/49), suggesting hepatic fibrosis, and it correlated with BMI and GGT. Patients with pathogenic variants in BBS10 showed a tendency towards higher ATI, reduced GFR, and higher BMI SDS. We detected kidney and liver abnormalities in a higher percentage of BBS patients than previously reported, indicating a high sensitivity and diagnostic yield of the evaluated high-end US applications. ATI detected liver pathology early (partially prior to liver enzymes) and revealed differences related to the affected genes. Evidence of tissue pathology at an early stage may improve diagnostics and the evaluation of therapeutic approaches.

Abstract 4135869: Local Ethanol Infusion after Pulsed Field Ablation Enhances Acute Efficacy of In Vivo Ventricular Electroporation

Background: Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias. Hypothesis: We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles. Methods: The ventricles of five porcine subjects were ablated in vivo with a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics. Results: A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced ( Figure 1A ). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets ( Figure 1A-B ). Conclusion: Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.

Abstract 4116300: Valvular Abnormalities and Risk of Abdominal Aortic Aneurysm Associated with Fluoroquinolone Use; A Retrospective Cohort Study

Introduction: Fluoroquinolones (FQ) are efficacious antibiotics whose antimicrobial effect is achieved through bacterial DNA gyrase inhibition. However, there is evidence suggesting that FQ may cause impaired collagen synthesis and an increase in tissue collagen degradation. Collagen serves as a predominant structural constituent of the aortic wall and heart valves. These structures undergo tissue maintenance, which necessitates the regulated expression of MMPs and TGF-β. In this study, we hypothesized that prolonged usage of FQs may increase risk of valvular abnormalities and abdominal aortic aneurysm. Methods: We conducted a retrospective cohort study utilizing de-identified patient data from the TriNetX platform, an extensive electronic health records (EHR) system. The cohorts consisted of smoker patients who used FQs for more than two consecutive weeks, Cohort A, N= 352,215 and smoker patients without a history of FQ use, Cohort B, N=350,912. Propensity score matching balanced baseline characteristics between cohorts: age, sex, ethnicity, and comorbidities. Results: The risk of developing AAA among smokers with a history of FQ use was 1.222% while the risk was 0.806% among smokers without history of FQ use (P&lt; 0.0001, 95% CI (0.63,0.691), Risk Ratio (RR)= 0.66). The risk of developing nonrheumatic (NR) aortic insufficiency among smokers with history of FQ use was 1.479% while smokers with no history of fluoroquinolone use had a 0.95% risk (P&lt;&lt;0.0001, 95% CI (0.616,0.67), RR= 0.643). The risk of developing NR mitral insufficiency in smokers with history of FQ use was 3.873% versus their smoker FQ naive counterparts risk of 2.317% (P&lt; 0.0001, 95% CI (0.582,0.615), RR= 0.598). NR tricuspid insufficiency in smokers with FQ usage was also increased versus their smoker FQ naive counterparts at 3.089% and 1.758%, respectively (P&lt; 0.0001, 95% CI (0.552,0.587), RR =0.569). Conclusions: This study uncovered a significant association between FQ use, risk of AAA, and NR-valvular insufficiencies among smokers. In particular, male smokers are at highest risk of developing AAA. This same population is at risk for prostatitis that would likely need treatment with FQs, further increasing their risk. Despite the efficacy of this class of antibiotics, caution is paramount when prescribing FQs in individuals who are actively smoking or have any connective tissue pathologies.

Protective Role of Cepharanthine Against Equid Herpesvirus Type 8 Through AMPK and Nrf2/HO-1 Pathway Activation

Equid herpesvirus type 8 (EqHV-8) is known to cause respiratory disease and miscarriage in horses and donkeys, which is a major problem for the equine farming industry. However, there are currently limited vaccines or drugs available to effectively treat EqHV-8 infection. Therefore, it is crucial to develop new antiviral approaches to prevent potential pandemics caused by EqHV-8. This study evaluates the antiviral and antioxidant effects of cepharanthine against EqHV-8 by employing both in vitro assays and in vivo mouse models to assess its therapeutic efficacy. To assess the effectiveness of cepharanthine against EqHV-8, we conducted experiments using NBL-6 and RK-13 cells. Additionally, we developed a mouse model to validate cepharanthine’s effectiveness against EqHV-8. In our in vitro experiments, we assessed the cepharanthine’s ability to inhibit infection caused by EqHV-8 in NBL-6 and RK-13 cells. Our results demonstrated that cepharanthine has a dose-dependent inhibitory effect, indicating that it possesses anti-EqHV-8 properties at the cellular level. Moreover, we investigated the mechanism through which cepharanthine exerts its protective effects. It was observed that cepharanthine effectively reduces the oxidative stress induced by EqHV-8 by activating the AMPK and Nrf2/HO-1 signaling pathways. Furthermore, when administered to EqHV-8 infected mice, cepharanthine significantly improved lung tissue pathology and reduced oxidative stress. The findings presented herein collectively highlight cepharanthine as a promising candidate for combating EqHV-8 infections.

Mass Spectrometry Advances in Analysis of Glioblastoma.

Some cancers such as glioblastoma (GBM), show minimal response to medical interventions, often only capable of mitigating tumor growth or alleviating symptoms. High metabolic activity in the tumor microenvironment marked by immune responses and hypoxia, is a crucial factor driving tumor progression. The many developments in mass spectrometry (MS) over the last decades have provided a pivotal tool for studying proteins, along with their posttranslational modifications. It is known that the proteomic landscape of GBM comprises a wide range of proteins involved in cell proliferation, survival, migration, and immune evasion. Combination of MS imaging and microscopy has potential to reveal the spatial and molecular characteristics of pathological tissue sections. Moreover, integration of MS in the surgical process in form of techniques such as DESI-MS or rapid evaporative ionization MS has been shown as an effective tool for rapid measurement of metabolite profiles, providing detailed information within seconds. In immunotherapy-related research, MS plays an indispensable role in detection and targeting of cancer antigens which serve as a base for antigen-specific therapies. In this review, we aim to provide detailed information on molecular profile in GBM and to discuss recent MS advances and their clinical benefits for targeting this aggressive disease.

Curcumin ameliorates heatstroke-induced lung injury by activating the PI3K/AKT pathway.

Heatstroke (HS) poses a significant threat to public health. Curcumin, a polyphenolic compound, has been reported to possess anti-inflammatory and antioxidant properties. This study aimed to investigate the potential therapeutic effects of curcumin on HS-induced lung injury and to elucidate its underlying molecular mechanisms. We utilized network pharmacology to predict the potential targets of curcumin and determine its possible protective effects against HS. Molecular docking was performed to assess the affinity of curcumin to proteins. Forty mice were used for in vivo experiments to evaluate the therapeutic effects of curcumin, divided into four groups (n = 10 per group): normal control (NC), high-temperature control (HTC), low-dose curcumin heatstroke (H100c, 100mg/kg/day), and high-dose curcumin heatstroke (H200c, 200mg/kg/day). Furthermore, we evaluated lung pathology, ultrastructural alterations, and protein expression levels of key molecules. Molecular docking indicated a high binding affinity between curcumin and PIK3R1, AKT, and CASP3. In vivo experiments confirm that curcumin pretreatment significantly mitigates HS-induced lung tissue pathology and ultrastructural damage, with the H200c group showing notably greater improvement. Furthermore, curcumin pretreatment markedly enhances the activation of the PI3K/AKT pathway and suppresses the expression of cleaved caspase3, particularly in the H200c group. Our study suggests curcumin may alleviate HS-induced lung injury via the PI3K/AKT pathway, but limitations exist. We did not test key protein knockdown/overexpression, and PI3K/AKT may not be the only pathway. Human and mouse pharmacokinetic differences could affect clinical translation.

Mesenchymal stem cell application in pulmonary disease treatment with emphasis on their interaction with lung-resident immune cells

Due to the vital importance of the lungs, lung-related diseases and their control are very important. Severe inflammatory responses mediated by immune cells were among the leading causes of lung tissue pathology and damage during the COVID-19 pandemic. In addition, uncontrolled immune cell responses can lead to lung tissue damage in other infectious and non-infectious diseases. It is essential to control immune responses in a way that leads to homeostasis. Immunosuppressive drugs only suppress inflammatory responses and do not affect the homeostasis of reactions. The therapeutic application of mesenchymal stem cells (MSCs), in addition to restoring immune homeostasis, can promote the regeneration of lung tissue through the production of growth factors and differentiation into lung-related cells. However, the communication between MSCs and immune cells after treatment of pulmonary diseases is essential, and investigating this can help develop a clinical perspective. Different studies in the clinical phase showed that MSCs can reverse fibrosis, increase regeneration, promote airway remodeling, and reduce damage to lung tissue. The proliferation and differentiation potential of MSCs is one of the mechanisms of their therapeutic effects. Furthermore, they can secrete exosomes that affect the function of lung cells and immune cells and change their function. Another important mechanism is that MSCs reduce harmful inflammatory responses through communication with innate and adaptive immune cells, which leads to a shift of the immune system toward regulatory and hemostatic responses.

Scalable deep learning artificial intelligence histopathology slide analysis and validation.

Deep learning involves an artificial intelligence (AI) approach and has been shown to provide superior performance for automating image recognition tasks, as well as exceeding human capabilities in both time and accuracy. Histopathology diagnostics is one of the more popular challenges at the intersection of artificial intelligence, computer vision, and medicine. Developing methods to automatically detect and identify pathologies in digitized histology slides imposes unique challenges due to the large size of these images and the complexity of the features present in biological tissue. Most methods that are capable of human-level recognition in histopathology are tuned to a specific problem since the computational complexity exceeds that of traditional image classification problems. In the current study, a deep learning approach is developed and presented that can be trained to locate and accurately classify different types of pathologies in gigapixel digitized histology slides along with completing the binary disease classification for the entire image. The approach uses a novel pyramid tiling approach to take advantage of spatial awareness around the area to be classified, while maintaining efficiency and scalability for gigapixel images. The approach is trained and validated on a wide variety of tissue types (i.e., testis, ovary, prostate, kidney) and pathologies taken from an epigenetically altered histology study at Washington State University. The newly developed procedure was optimized and validated along with comparison and validation on public histology datasets. The current developed procedure was found to be optimal and more reproducible when compared to manual procedures, and optimal to previous protocols that used fragmented tissue or slide analysis. Observations demonstrate that the deep learning histopathology analysis is significantly more efficient and accurate than standard manual histopathology analysis.

Photobiomodulation Therapy at 660 nm Inhibits Hippocampal Neuroinflammation in a Lipopolysaccharide-Challenged Rat Model

Background/Objectives: Neuroinflammation is associated with the progression of various brain diseases, and the management of neuroinflammation-induced neural damage is a crucial aspect of treating neurological disorders. This study investigated the anti-inflammatory efficacy of photobiomodulation therapy (PBMT) using 660 nm phototherapy in a rat model with lipopolysaccharide (LPS)-induced neuroinflammation. Methods: We induced inflammation in rat brains via intraperitoneal injection of LPS and subjected the treatment group to 660 nm phototherapy to examine its protective effect against hippocampal damage based on pathological, histological, and immunohistochemical tissue analyses. Results: The 660 nm treated rats showed a significant decrease in hippocampal structural damage and cell death compared to the LPS-treated group. We observed reduced expression of the inflammation markers GFAP, TNF-α, and IL-1β in the hippocampus of the treatment group, and an increase in SIRT1 expression across all hippocampal regions. Conclusions: This study presents a promising method for controlling neuroinflammation and providing neuroprotection and inflammation relief. PBMT represents a non-invasive therapeutic approach with minimal side effects ensured through the proper control of light irradiation.

Peptide stimulation effect on organotypic culture development of neuroendocrine tissues

Introduction. One of the actual task of modern biology and medicine. Is the creation of bioregulator preparation, which can stimulate the neuroendocrine system of organism. Purpose of study. Study of effect of polypeptide complex from brain cortex (PPCbc) and from pancreas (PPCp) of calfs on the cellular proliferation in organotypic culture of nerve and endocrine of young and old rats. Methods. The adequate method of organotypic tissue culture of tissue from young and old rats was used for quick biologically activity of peptides screening. Results. The square index (SI) of nerve and endocrine tissues explants were increased statistically reliable, as compared to the control, also in young and old rats, under the polypeptides complexes effect. Conclusion. The data obtained produce the base for working and quick testing of preparations for treatment of patients with pathology in brain cortex and endocrine tissues

Stigmas of dysembryogenesis of undifferentiated connective tissue dysplasia in bronchial asthma

Connective tissue dysplasia is a disturbance of its development during embryogenesis and the postnatal period due to genetically altered fibrillogenesis of the extracellular matrix. Undifferentiated connective tissue dysplasia (UCTD) includes a set of phenotypic characteristics that do not fit into any already known dysplastic syndrome or phenotype. It is this pathology of connective tissue that is widespread and is constantly encountered in the practice of doctors of various profiles, serving as the basis for the formation of various chronic diseases. As for bronchial asthma (BA), it is quite natural that studies have appeared to identify the characteristics of the course of BA with connective tissue dysplasia, primarily in children. It has been shown that asthma in children associated with connective tissue dysplasia has a number of clinical features: an earlier onset of the disease, a higher incidence of concomitant diseases, and a more severe course. The features of the course of bronchial asthma associated with connective tissue dysplasia in adults have been practically not studied. Our very first results from a study of adult patients with BA showed that in patients with a mild course of the disease, up to 3 stigmas of disembryogenesis were recorded, in patients with a moderate course - from 2 to 4, and in patients with a severe course - from 1 to 8 stigmas. Correlation analysis (the data was obtained on a small material, therefore we do not consider it statistically significant) provides a distinct basis for continuing the study. Thus, negative correlations have been identified between the presence of stigmas (myopia, dolichostenomelia, joint hypermobility, wide atrophic scars, varicose veins) and such an important characteristic of the disease as its controllability.

“Exploring The Nexus”: Chronic musculoskeletal pain in diabetic vs non-diabetic population

IntroductionDiabetes-mellitus (DM) has transcended the boundaries and affected populations across globe, it predisposes individual to stiffness and musculoskeletal-pain due to accumulation of glycation-end-products. Musculoskeletal-pain is a common yet frequently neglected complication. Pain mechanisms have been categorized as nociceptive, neuropathic, nociplastic, and idiopathic. Four criteria were put by Kosek-et-al to identify nociplastic pain that affects the musculoskeletal-system. Study aimed to evaluate prevalence of chronic musculoskeletal (cMSK) pain and its association with diabetes and glycaemic control and to evaluate comorbid conditions of cMSK pain. Methods and materialsA prospective case-control study was conducted at a level-1-tertiary-care-facility. Patients with type-2 DM above 30-years-age who visited outpatient department participated in the study (study group). Age-matched equal number of healthy individuals (control-cohort) were recruited in the study. We collected data from 300 participants in each group. Analysis was done based-on HbA1c-levels, random-blood-sugar (RBS),clinical-history, and comorbidities. Information regarding cMSK-pain was gathered using modified version of Nordic standard questionnaire. ResultsOverall prevalence of cMSK pain was 23.3 % (140 out of 600). Among Group-1/Diabetic group, it was 27.7 % and among group-2/Healthy Cohort it was 19 % and the odds ratio was 1.6. Most commonly reported region with cMSK among group-1 and group-2 was shoulder (32.5 %) and knee (36.8 %) respectively. We found a significant association between cMSK-pain and HbA1c levels (p < 0.005). and individuals with HbA1c levels of more than 12 reported involvements in multiple regions. We didn't find significant association between cMSK and DM, HTN, dyslipidemia, or hypothyroidism (P > 0.05). ConclusionStudy highlights higher-prevalence and significant impact of cMSK pain in diabetic patients compared to non-diabetic individuals. Addressing musculoskeletal-pain is crucial for improving overall quality-of-life in diabetic patients. Clinicians should adopt a proactive and comprehensive approach to pain management in diabetics. Using a simple Nordic questionnaire during routine check-ups helps with screening of joint and surrounding soft tissue pathology, preventing future complications that could lead to disability.

A rare case of prostatic malakoplakia with multidrug-resistant Escherichia coli: a case report

Prostatic malakoplakia is an uncommon chronic inflammatory disorder, tumor-like but non-cancerous, the diagnosis of which pivots crucially on the identification of characteristic Michaelis-Gutmann bodies within the pathological tissue. We hereby present an inaugural case report of prostatic malakoplakia concurrent with sepsis caused by multidrug-resistant Escherichia coli, verified through blood culture and metagenomic next-generation sequencing (mNGS). The pathogenesis might be associated with infections by Escherichia coli, immune system irregularities, or lysosomal dysfunction. Although the patient had no chronic underlying diseases, he presented early with sepsis and multi-organ dysfunction. This case emphasizes the imperative to further investigate the association between malakoplakia and Escherichia coli, the necessity for prompt diagnosis, and the supportive role of mNGS, and the treatment strategy focuses on rapid control of infection and systemic inflammatory response.

The role of extracellular ATP in regulating the functional activity of cells

A search and analysis of scientific articles presented in the databases PubMed, ScienceDirect, Elsevier, eLibrary for 2000–2024 was carried out. The selection criterion was the presence in the articles of information on the concentration of extracellular ATP in normal and pathological tissues, the mechanisms of purinergic regulation of cell functioning, and the expression of CD73 and CD39 ectonucleotidases on cells, which regulate proinflammatory extracellular ATP catabolism to immunosuppressive adenosine. Modern data are presented on the role of extracellular ATP in the regulation of cell functioning under normal and pathological conditions, during inflammation and the formation of cellular and humoral immune responses, as well as on the study of the mechanisms of purinergic signaling from extracellular ATP in the development of targeted drugs for various diseases, including neoplasms, neurodegenerative and autoimmune pathologies.