Animal Studies Research Articles

Sex-related differences in efficacy of bone marrow-derived high aldehyde dehydrogenase activity cells against pulmonary fibrosis

BackgroundAlthough bone marrow-derived cells with high aldehyde dehydrogenase activity (ALDHbr) have shown therapeutic potential against various diseases in animal studies, clinical trials have failed to show concurrent findings. We aimed to clarify the optimal conditions for the efficacy of ALDHbr cells by using a murine bleomycin-induced pulmonary fibrosis model.MethodsWe intravenously transferred male or female donor C57BL/6 mice-derived ALDHbr cells into recipient C57BL/6 mice under various conditions, and used mCherry-expressing mice as a donor to trace the transferred ALDHbr cells.ResultsPulmonary fibrosis improved significantly when (1) female-derived, not male-derived, and (2) lineage (Lin)-negative, not lineage-positive, ALDHbr cells were transferred during the (3) fibrotic, not inflammatory, phase. Consistent with the RNA-sequencing results, female-derived Lin−/ALDHbr cells were more resistant to oxidative stress than male-derived cells in vitro, and transferred female-derived Lin−/ALDHbr cells were more viable than male-derived cells in the fibrotic lung. The mechanism underlying the antifibrotic effects of Lin−/ALDHbr cells was strongly associated with reduction of oxidative stress.ConclusionsOur results indicated that Lin−/ALDHbr cell therapy could ameliorate pulmonary fibrosis by reducing oxidative stress and suggested that their efficacy was mediated by sex-related differences. Thus, sex-awareness strategies may be important for clinical application of bone marrow ALDHbr cells as a therapeutic tool.

Osteoporosis Management for Shoulder Surgeons.

The aim of this review is to aggregate currently available literature as it pertains to treating surgical shoulder pathology in patients with osteoporosis. Emerging data surrounding perioperative use of anti-osteoporosis medications for patients undergoing shoulder surgery have not shown definitively favorable or unfavorable outcomes. Similar evaluations in animal studies have shown promising results as a biologic augment to tendon and bone healing, especially with newer, anabolic agents. The mainstay of bone health management remains pre-operative evaluation, using opportunistic radiographic and CT based validated measurements, along with optimization of risk factors. Surgical techniques continue to incorporate implants that perform well in osteopenic bone. Promising pre-clinical studies have identified anabolic anti-osteoporosis medications as viable biologic augments to shoulder surgery, which has not been borne out in any clinical studies at this time.

The potential of nanocomposites (patuletin-conjugated with gallic acid-coated zinc oxide) against free-living amoebae pathogens.

Free-living amoebae infections are on the rise while the prognosis remains poor. Current therapies are ineffective, and there is a need for novel effective drugs which can target Naegleria, Balamuthia, and Acanthamoeba species. In this study, we determined the effects of a nano-formulation based on flavonoid patuletin-loaded gallic acid functionalized zinc oxide nanoparticles (PA-GA-ZnO) against Acanthamoeba, Balamuthia, and Naegleria trophozoites. Characterization of the nano-formulation was accomplished utilizing analytical tools, namely Fourier-transform infrared spectroscopy, drug entrapment efficiency, polydispersity index, dimensions, and surface morphologies. Anti-amoebic effects were investigated using amoebicidal assay, cytopathogenicity assay, and cytotoxicity of the nano-formulation on human cells. The findings revealed that nano-formulation (PA-GA-ZnO) displayed significant anti-amoebic properties and augmented effects of patuletin alone against all three brain-eating amoebae. When tested alone, patuletin nano-formulations showed minimal toxicity effects against human cells. In summary, the nano-formulations evaluated herein depicts efficacyversusAcanthamoeba, Balamuthia, and Naegleria. Nonetheless, future studies are needed to comprehend the molecular mechanisms of patuletin nano-formulations versus free-living amoebae pathogens, in addition to animal studies to determine their potential value for clinical applications.

#BrazilianButtLift: The Reel Problem Regarding Gluteal Augmentation Surgery.

This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Lesion-localized hydrogels functionalized with engineered extracellular matrix restore cellular homeostasis by enhancing mitochondrial energy metabolism for osteoarthritis therapy

Cartilage damage and degeneration are fundamental pathological features of osteoarthritis (OA), attributed largely to disruptions in chondrocyte homeostasis. Tissue engineering employing functional bioactive materials presents a promising avenue for cartilage regeneration and repair. Particularly, extracellular matrix (ECM) produced by mesenchymal stem cells (MSCs) is gaining traction in the field of tissue engineering and scaffold-based regenerative therapies due to its robust bioactivity and excellent biocompatibility. In this study, we utilized specific inflammatory cytokines associated with OA as stimulators to optimize the MSC-derived secretome. Our in vitro experiments demonstrated that the engineered ECM effectively inhibited early chondrocyte apoptosis, reversed cellular senescence, and maintained anabolic-catabolic equilibrium. Moreover, we developed aldehyde- and methacrylic anhydride-modified hyaluronic acid hydrogels incorporated with ECM (ECM@AH) using photo-cross-linking techniques. The affinity of these ECM-functionalized hydrogels for degraded cartilage was confirmed through in situ cartilage lesion localization experiments in the knee joints of rat OA models. Further in vitro analysis revealed that the engineered ECM@AH, especially IFN-γ-ECM@AH, sustains chondrocyte homeostasis by restoring mitochondrial energy metabolism. Animal studies demonstrated that ECM@AH, localized to cartilage lesions, could reverse cartilage matrix degradation and promote cartilage repair, underscoring the potential of this biomaterial in OA treatment.

Altered firing output of VIP interneurons and early dysfunctions in CA1 hippocampal circuits in the 3xTg mouse model of Alzheimer's disease.

Alzheimer's disease (AD) leads to progressive memory decline, and alterations in hippocampal function are among the earliest pathological features observed in human and animal studies. GABAergic interneurons (INs) within the hippocampus coordinate network activity, among which type 3 interneuron-specific (I-S3) cells expressing vasoactive intestinal polypeptide and calretinin play a crucial role. These cells provide primarily disinhibition to principal excitatory cells (PCs) in the hippocampal CA1 region, regulating incoming inputs and memory formation. However, it remains unclear whether AD pathology induces changes in the activity of I-S3 cells, impacting the hippocampal network motifs. Here, using young adult 3xTg-AD mice, we found that while the density and morphology of I-S3 cells remain unaffected, there were significant changes in their firing output. Specifically, I-S3 cells displayed elongated action potentials and decreased firing rates, which was associated with a reduced inhibition of CA1 INs and their higher recruitment during spatial decision-making and object exploration tasks. Furthermore, the activation of CA1 PCs was also impacted, signifying early disruptions in CA1 network functionality. These findings suggest that altered firing patterns of I-S3 cells might initiate early-stage dysfunction in hippocampal CA1 circuits, potentially influencing the progression of AD pathology.

Carcinomembrane-Camouflaged Perfluorochemical Dual-Layer Nanopolymersomes Bearing Indocyanine Green and Camptothecin Effectuate Targeting Photochemotherapy of Cancer.

Photochemotherapy has been recognized as a promising combinational modality for cancer treatment. However, difficulties such as off-target drug delivery, systemic toxicity, and the hypoxic nature of the tumor microenvironment remain hindrances to its application. To overcome these challenges, cancer cell membrane camouflaged perfluorooctyl bromide (PFOB) dual-layer nanopolymersomes bearing indocyanine green (ICG) and camptothecin (CPT), named MICFNS, were developed in this study, and melanoma was exploited as the model for MICFNS manufacture and therapeutic application. Our data showed that MICFNS were able to stabilize both ICG and CPT in the nanocarriers and can be quickly internalized by B16F10 cells due to melanoma membrane-mediated homology. Upon NIR irradiation, MICFNS can trigger hyperthermia and offer enhanced singlet oxygen production due to the incorporation of PFOB. With ≥10/2.5 μM ICG/CPT, MICFNS + NIR can provide comparable in vitro cancericidal effects to those caused by using an 8-fold higher dose of encapsulated CPT alone. Through the animal study, we further demonstrated that MICFNS can be quickly brought to tumors and have a longer retention time than those of free agents in vivo. Moreover, the MICFNS with 40/10 μM ICG/CPT in combination with 30 s NIR irradiation can successfully inhibit tumor growth without systemic toxicity in mice within the 14 day treatment. We speculate that such an antitumoral effect was achieved by phototherapy followed by chemotherapy, a two-stage tumoricidal process performed by MICFNS. Taken together, we anticipate that MICFNS, a photochemotherapeutic nanoplatform, has high potential for use in clinical anticancer treatment.

Riotous methodological and methodointuitive reflections on (non)religion, spirituality and the multispecies turn

The ‘multispecies turn’ in the social sciences and humanities is informing many disciplines including animal studies, anthropology, Indigenous studies and, more recently, sociology of religion. Scholars working on multispecies relations employ various methods and methodologies, many of which are challenging modern, Western, Christian paradigms and practices that are anthropocentric and focus on logos/words/texts/beliefs. This discussion examines new and multiple ways of conducting multispecies focused research, that is critical, reflexive, embodied, affective and intuitive. It begins with an overview of the methods applied by notable scholars – Kimmerer, Tsing and Beaman – researching multispecies relations, and then includes four personal ‘riotous’ reflections by this article’s co-authors, on their own positionality and experiences of conducting such research. The discussion concludes by identifying key challenges in research on diverse worldviews and multispecies relations, and aims to generate creative and scientific responses to further decenter anthropocentrism in academia.

The Protective Effect of Adipose Derived Stromal Vascular Fraction on Ovarian Function in Rats with Cyclophosphamide-Induced Ovarian Damage.

To investigate if adipose derived stromal vascular fraction (SVF) treatment has any protective effect on ovarian function in rats with cyclophosphamide (CP) induced ovarian damage. Experimental animal study. Participants/ Materials, Setting, Methods: 25 mature cycling Wistar-Albino rats were randomized into four groups (n=5 per group). Rats in Group 1 and 2 received single dose of intraperitoneal (i.p.) 1 mL/kg sodium chloride 0.9% (NaCl). Group 3 and 4 received single dose of 75 mg/kg i.p. CP. On seventh day, SVF was prepared from adipose tissues of 5 additional rats and Group 1 and 3 received 0.9% NaCl i.p. injections while Group 2 and 4 received 0.2 mL i.p. injections of SVF. On day 21 all rats were euthanized, and serum anti-mullerian hormone (AMH) levels, primordial, primary, secondary, antral, and atretic follicle counts, AMH positive staining follicle counts along with AMH staining intensity of the follicles were evaluated. Among two CP induced ovarian damaged groups, SVF treated group showed significantly higher secondary and antral follicle and lower atretic follicle counts, significantly higher mean serum AMH levels, AMH positive antral follicle count and higher intensity of AMH positive follicle scores for primary, secondary and antral follicles when compared to untreated group. Moreover, Group 1 showed no significant difference for all parameters except antral follicle count and AMH positive staining intensity scores for antral follicles when compared to Group 4. This study was conducted on experimental rat model. Our study demonstrated a significant protective effect of SVF against Cp-induced ovarian damage which reveals the apparent need for further investigation of its precise mechanisms of action as it may provide a new treatment approach for women with premature ovarian failure.

Dietary Fat Intake on Metabolic Health: An in-Depth Analysis of Epidemiological, Clinical, and Animal Studies

Dietary Fat Intake on Metabolic Health: An in-Depth Analysis of Epidemiological, Clinical, and Animal Studies

In vivo video microscopy of the rupturing process of thin blood vessels to clarify the mechanism of bruising caused by blunt impact: an animal study

BackgroundThe thresholds of mechanical inputs for bruising caused by blunt impact are important in the fields of machine safety and forensics. However, reliable data on these thresholds remain inadequate owing to a lack of in vivo experiments, which are crucial for investigating the occurrence of bruising. Since experiments involving live human participants are limited owing to ethical concerns, finite-element method (FEM) simulations of the bruising mechanism should be used to compensate for the lack of experimental data by estimating the thresholds under various conditions, which requires clarifying the mechanism of formation of actual bruises. Therefore, this study aimed to visualize the mechanism underlying the formation of bruises caused by blunt impact to enable FEM simulations to estimate the thresholds of mechanical inputs for bruising.MethodsIn vivo microscopy of a transparent glass catfish subjected to blunt contact with an indenter was performed. The fish were anesthetized by immersing them in buffered MS-222 (75–100 mg/L) and then fixed on a subject tray. The indenter, made of transparent acrylic and having a rectangular contact area with dimensions of 1.0 mm × 1.5 mm, was loaded onto the lateral side of the caudal region of the fish. Blood vessels and surrounding tissues were examined through the transparent indenter using a microscope equipped with a video camera. The contact force was measured using a force-sensing table.ResultsOne of the processes of rupturing thin blood vessels, which are an essential component of the bruising mechanism, was observed and recorded as a movie. The soft tissue surrounding the thin blood vessel extended in a plane perpendicular to the compressive contact force. Subsequently, the thin blood vessel was pulled into a straight configuration. Next, it was stretched in the axial direction and finally ruptured.ConclusionThe results obtained indicate that the extension of the surrounding tissue in the direction perpendicular to the contact force as well as the extension of the thin blood vessels are important factors in the bruising mechanism, which must be reproduced by FEM simulation to estimate the thresholds.

Implications of β-Arrestin biased signaling by angiotensin II type 1 receptor for cardiovascular drug discovery and therapeutics

Angiotensin II receptors, Type 1 (AT1R) and Type 2 (AT2R) are 7TM receptors that play critical roles in both the physiological and pathophysiological regulation of the cardiovascular system. While AT1R blockers (ARBs) have proven beneficial in managing cardiac, vascular and renal maladies they cannot completely halt and reverse the progression of pathologies. Numerous experimental and animal studies have demonstrated that β-arrestin biased AT1R-ligands (such as SII-AngII, S1I8, TRV023, and TRV027) offer cardiovascular benefits by blocking the G protein signaling while retaining the β-arrestin signaling. However, these ligands failed to show improvement in heart-failure outcome over the placebo in a phase IIb clinical trial. One major limitation of current β-arrestin biased AT1R-ligands is that they are peptides with short half-lives, limiting their long-term efficacy in patients. Additionally, β-arrestin biased AT1R-ligand peptides, may inadvertently block AT2R, a promiscuous receptor, potentially negating its beneficial effects in post-myocardial infarction (MI) patients. Therefore, developing a small molecule β-arrestin biased AT1R-ligand with a longer half-life and specificity to AT1R could be more effective in treating heart failure. This approach has the potential to revolutionize the treatment of cardiovascular diseases by offering more sustained and targeted therapeutic effects.

First Fully Endoscopic End-to-End Colonic Anastomoses With a Novel Endoscopic Device: A Feasibility Study in a Porcine Model.

Continuous advancements and breakthroughs in flexible gastrointestinal endoscopy have led to alternatives to colonic anastomosis. This study aimed to evaluate the feasibility and safety of end-to-end colonic anastomosis using a single flexible endoscope with the novel through-the-scope "bow-tie" (TTS-BT) device and conventional metal clips in a porcine model. Animal study. Animal laboratory at China Medical University. Eight healthy pigs were included. Eight animals underwent total colonic severance and anastomoses with through-the-scope "bow-tie" devices and metal clips. The primary outcomes were the success rate of the anastomosis and survival rate during 3-month follow-up. Furthermore, the secondary outcomes were anastomotic site healing, reintervention rate, and rate of anastomotic complications such as bleeding, leakage, stenosis, and obstruction. Six pigs were euthanized, and necropsies were performed 3 months postoperatively, while two pigs were fed for long-term observation. The anastomotic stoma was histologically analyzed using Hematoxylin-eosin and Masson's trichrome staining. End-to-end colonic anastomoses were successfully performed using through-the-scope "bow-tie" devices, and satisfactory healing was achieved in all pigs. The success rate of anastomosis was 100% (8/8). All animals survived postoperatively without anastomotic complications, including bleeding, leakage, or obstruction; however, two cases of stenosis occurred (25%), and one case (12.5%) required reintervention. Large-scale studies should be conducted to verify the feasibility and safety of the through-the-scope "bow-tie" device in other parts of the intestine. Flexible endoscopy with the through-the-scope "bow-tie" device is feasible and safe for intraluminal colonic anastomosis. This study may expand the indications for full-thickness endoscopic resection in the future. See Video abstract.

Three-dimensional virtual histology of the rat uterus musculature using micro-computed tomography.

Contractions of the uterus play an important role in menstruation and fertility, and contractile dysfunction can lead to chronic diseases such as endometriosis. However, the structure and function of the uterus are difficult to interrogate in humans, and thus animal studies are often employed to understand its function. In rats, anatomical studies of the uterus have typically been based on histological assessment, have been limited to small segments of the uterine structure, and have been time-consuming to reconstruct at the organ scale. This study used micro-computed tomography imaging to visualise the muscle structures in the entire non-pregnant rat uterus and assess its use for 3D virtual histology. An assessment of the rodent uterus is presented to (i) quantify muscle thickness variations along the horns, (ii) identify predominant fibre orientations of the muscles and (iii) demonstrate how the anatomy of the uterus can be mapped to 3D volumetric meshes via virtual histology. Micro-computed tomography measurements were validated against measurements from histological sections. The average thickness of the myometrium was found to be 0.33 ± 0.11 mm and 0.31 ± 0.09 mm in the left and right horns, respectively. The micro-computed tomography and histology thickness calculations were found to correlate strongly at different locations in the uterus: at the cervix, r = 0.87, and along the horn from the cervical end to the ovarian end, respectively, r = 0.77, r = 0.89 and r = 0.54, with p < 0.001 in every location. This study shows that micro-computed tomography can be used to quantify the musculature in the whole non-pregnant uterus and can be used for 3D virtual histology.

Current Utilization and Research Status of Herbal Medicine Sipjeondaebotang for Anemia: A Scoping Review

Background/Objectives: Anemia is a global health issue affecting diverse populations, particularly older adults, and conventional treatments often show limited efficacy. This study aimed to evaluate the utilization and effectiveness of Sipjeondaebotang (SDT), a prescription drug used in traditional East Asian medicine, in treating various types of anemia. Methods: A scoping review was conducted following Arksey and O’Malley’s framework and PRISMA-ScR guidelines. Six electronic databases were searched for clinical studies on SDT, while focusing on human participants and excluding animal and cellular studies. Sixteen studies, including nine randomized controlled trials, two controlled clinical trials, two case series, and three case reports, involving 863 participants, were analyzed. These studies were primarily conducted in China, Korea, and Japan. Results: According to the analysis, SDT improved hemoglobin levels across all types of anemia studied, with all controlled studies showing significant improvements compared with the control groups. Additionally, SDT reduced blood loss, improved recovery times, and decreased transfusion requirements in patients with post-operative anemia, with lower adverse event rates than those in the control groups. These findings suggest that SDT may enhance hematological parameters and improve overall patient outcomes. Conclusions: In conclusion, SDT may be an effective treatment for anemia that improves hemoglobin levels and patient outcomes. However, further high-quality, large-scale studies are necessary to standardize SDT prescriptions, confirm the optimal treatment duration, and validate its efficacy and safety across different anemia types.

Apple cider vinegar in folk and modern medicine: a historical review and current scientific evidence.

Introduction and Aim of the Study: Apple cider vinegar (ACV) has been used for centuries in various cultural and medical contexts globally. This study seeks to explore ACV's traditional and contemporary applications, evaluating scientific evidence for its efficacy and safety. Material and Methods: This review synthesizes information from PubMed, Google Scholar, and other scientific sources. Key search terms included "apple cider vinegar," "apple cider vinegar medical use," "apple cider vinegar antimicrobial effect," "apple cider vinegar lipid profile," "apple cider vinegar glucose level," "apple cider vinegar preparation," and "apple cider vinegar historical use." Results: Research supports ACV's traditional role as a disinfectant, demonstrating effectiveness against a range of bacteria and fungi. Both animal and human studies suggest ACV may help lower cholesterol and triglyceride levels while boosting HDL cholesterol. Evidence indicates ACV can enhance insulin sensitivity and reduce blood glucose levels, offering benefits for type 2 diabetes management. ACV shows antioxidant properties, potential for lowering blood pressure, and use in certain skin diseases, though further research is needed to confirm these effects. Conclusions: The historical use of ACV in traditional medicine finds partial support in modern scientific research. Its antimicrobial, lipid-modulating, and glucose-regulating properties are documented, suggesting potential benefits for cardiovascular health, weight management, and metabolic regulation. Nonetheless, the evidence for its cosmetic applications and impact on muscle cramps remains less definitive. Additional research involving larger, diverse populations is necessary to fully validate ACV's benefits and establish safe usage guidelines.

Cancer-associated fibroblast cell surface markers as potential biomarkers or therapeutic targets in lung cancer

Cancer-associated fibroblasts (CAFs) are the vital constituent of the tumor microenvironment, and in communication with other cells, they contribute to tumor progression and metastasis. Fibroblasts are the proposed origin of CAFs, which are mediated by pro-inflammatory cytokines and the recruitment of immune cells akin to wound healing. Although various studies have identified different subpopulations of CAFs in lung cancer, the heterogeneity of CAFs, particularly in lung cancer, and their potential as a therapeutic target remain largely unknown. Notwithstanding CAFs were previously thought to have predominantly tumor-promoting features, their pro- or anti-tumorigenic properties may depend on various conditions and cell origins. The absence of distinct markers to identify CAF subpopulations presents obstacles to the successful therapeutic targeting and treatment of CAFs in cancer. Human clinical and animal studies targeting CAFs have shown that targeting CAFs exacerbates the disease progression, suggesting that subpopulations of CAFs may exert opposing functions in cancer progression. Therefore, it is essential to pinpoint specific markers capable of characterizing these subpopulations and revealing their mechanisms of function. The cell-specific surface markers of CAFs will serve as an initial step in investigating precise CAF subpopulations and their role in diagnosing and targeting therapy against cancer-promoting CAF subsets in lung cancer.

Microbiome contributions to pain: a review of the preclinical literature.

Over the past 2 decades, the microbiome has received increasing attention for the role that it plays in health and disease. Historically, the gut microbiome was of particular interest to pain scientists studying nociplastic visceral pain conditions given the anatomical juxtaposition of these microorganisms and the neuroimmune networks that drive pain in such diseases. More recently, microbiomes both inside and across the surface of the body have been recognized for driving sensory symptoms in a broader set of diseases. Microbiomes have never been a more popular topic in pain research, but to date, there has not been a systematic review of the preclinical microbiome pain literature. In this article, we identified all animal studies in which both the microbiome was manipulated and pain behaviors were measured. Our analysis included 303 unique experiments across 97 articles. Microbiome manipulation methods and behavioral outcomes were recorded for each experiment so that field-wide trends could be quantified and reported. This review specifically details the animal species, injury models, behavior measures, and microbiome manipulations used in preclinical pain research. From this analysis, we were also able to conclude how manipulations of the microbiome alter pain thresholds in naïve animals and persistent pain intensity and duration in cutaneous and visceral pain models. This review summarizes by identifying existing gaps in the literature and providing recommendations for how to best plan, implement, and interpret data collected in preclinical microbiome pain experiments.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review

Background Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. Methods We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. Results We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. Conclusion S. haematobium induces distinct alterations in the host’s immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection.

Disruption of Mitochondrial Quality Control in Inherited Metabolic Disorders.

Inherited metabolic disorders (IMDs) are genetic disorders often characterized by the accumulation of toxic metabolites in patient tissues and bodily fluids. Although the pathophysiologic effect of these metabolites and their direct effect on cellular function is not yet established for many of these disorders, animal and cellular studies have shown that mitochondrial bioenergetic dysfunction with impairment of citric acid cycle activity and respiratory chain, along with secondary damage induced by oxidative stress are prominent in some. Mitochondrial quality control, requiring the coordination of multiple mechanisms such as mitochondrial biogenesis, dynamics, and mitophagy, is responsible for the correction of such defects. For inborn errors of enzymes located in the mitochondria, secondary abnormalities in quality control this organelle could play a role in their pathophysiology. This review summarizes preclinical data (animal models and patient-derived cells) on mitochondrial quality control disturbances in selected IMDs.