Animal Studies Research Articles

EP74 Splenic function following angioembolisation for blunt splenic injury: A systematic review

Abstract Background Splenic artery angioembolisation (SAE) plays an important role in the nonoperative management of blunt splenic injury. In contrast to splenectomy, there is little guidance concerning immune function, and consequently the need for antimicrobial prophylaxis, following SAE. A systematic review was conducted to evaluate the current literature on the topic. Method A systematic review of the currently available literature was performed using the MEDLINE database. Original articles were eligible if they reported at least one marker of splenic function following SAE. Animal studies, literature reviews and case reports were excluded. Two researchers independently assessed the eligibility and quality of the articles and performed the data extraction; these studies were qualitatively analysed. Results Eleven studies were included. A total of 407 patients, of which 243 had undergone SAE, 80 who had undergone splenectomy and 84 healthy controls, were included. All studies used different parameters for assessing splenic function. None reported increased rates of infection or overwhelming postsplenectomy infection following SAE. There was no statistically significant difference between the markers of immunocompetence measured in the SAE group when compared to healthy controls. Ten of the studies concluded that, by the parameters they measured, splenic function was preserved after the procedure. Conclusion All but one of the included studies reported preserved splenic function following SAE. Whilst there is no single parameter that unequivocally demonstrates this, the best available evidence supports this. This may help inform clinical guidelines for post-SAE vaccination and prophylactic antibiotic practice; namely, that there is no indication to do so.

Assessing the Efficacy of Mitochondria-Accumulating Self-Assembly Peptides in Pancreatic Cancer: An Animal Study.

Although pancreatic cancer presents with one of the most unfavorable prognoses, its treatment options are very limited. Mitochondria-targeting moieties, considered a new and prominent treatment modality, are expected to demonstrate synergistic anticancer effects due to their distinct mechanism compared to conventional chemotherapeutic approaches. This study evaluated the therapeutic potential of mitochondria-accumulating self-assembly peptides, referred to as Mito-FFs, utilizing both in vitro and in vivo pancreatic cancer models. Cellular viability assays revealed a concentration-dependent decrease in the survival of MIA-PACA2 pancreatic cancer cells upon exposure to Mito-FF treatment (p < 0.05). Subsequent in vitro Mito-FF treatments prompted the use of several molecular analyses, including Real-time PCR, Western blot analysis, and MitoSOX staining, which collectively indicated an upsurge in apoptosis, a concurrent reduction in the antioxidant enzyme expression, and an elevation in mitochondrial ROS levels (p < 0.05). In a murine xenograft model of pancreatic cancer, the intravenous administration of Mito-FF yielded a notable reduction in the tumor volume. Moreover, it upregulated the expression of pro-apoptotic markers, such as cleaved PARP and c-caspase 3, while concurrently downregulating the expression of an anti-apoptotic marker, MCL-1, as evidenced by both Western blot analysis and immunohistochemical staining (p < 0.05). It also resulted in the reduced expression of antioxidant enzymes like HO-1, catalase, and SOD2 within excised tumor tissues, as confirmed using Western blot analysis (p < 0.05). Cumulatively, the findings underscore the significant anticancer efficacy of Mito-FF against pancreatic cancer cells, predominantly mediated through the induction of apoptosis, suppression of antioxidant enzyme expression, and enhancement of mitochondrial ROS levels within the tumor microenvironment.

Prevalence and Risk Factors of Waterborne and Foodborne Protozoan Pathogens in Kenya: A One Health Perspective.

Intestinal infections affect approximately 450 million people globally, predominantly impacting children and immunocompromised individuals in low- and middle-income countries (LMICs) due to inadequate water, sanitation, and hygiene (WASH) conditions, poverty, malnutrition, and low literacy. In Kenya, the prevalence of intestinal infections is elevated by warm tropical climates and socioeconomic factors. This scoping review evaluates the national prevalence, risk factors, and contamination sources of intestinal protozoa in Kenya, using a One Health approach to synthesize existing data from various human, animal, and environmental studies. A comprehensive literature search identified 292 studies, of which 67 met the inclusion criteria, covering the period from 1966 to 2024. The review found that most studies utilized stool microscopy, a method with limited sensitivity, and largely focused on vulnerable human populations, with minimal investigation into environmental reservoirs. Key protozoa identified included Entamoeba histolytica, Cryptosporidium, and Giardia, with transmission driven by poor WASH conditions, environmental factors, and close human-animal interactions. The findings highlight significant gaps in environmental surveillance and suggest the need for a robust, integrated One Health approach to better understand and control protozoan infections in Kenya.

Insights from animal studies exploring the efficacy and safety of topical losartan, in prophylaxis and treatment of corneal scarring fibrosis.

Several studies in rabbits demonstrated the efficacy and safety of topical losartan, an angiotensin II receptor blockers (ARB) that modulates the TGF-β intracellular signaling pathways by inhibiting the activation of Extracellular Signal-regulated Kinase (ERK), in preventing or treating stromal fibrosis after a range of injuries such as Descemetorhexis, alkali burns, incisions, and photorefractive keratectomy (PRK). Several case reports have shown that topical losartan treatment is also efficacious and safe in humans to prevent or treat stromal fibrosis after many different injuries or diseases. Topical losartan penetrates the full thickness of the cornea and, therefore, can treat both anterior and posterior stromal fibrosis. These rabbit studies have demonstrated that there can be epithelial and stromal toxicity to losartan at dosages greater than 0.8 mg/ml and that higher dosages will not accelerate the return to transparency of fibrotic corneas. In corneas with an epithelial defect, it is likely safer to use 0.2 mg/ml losartan six times a day until the epithelium closes to further decrease the risk of epithelial toxicity before going to the 0.8 mg/ml six times a day dosage. Future clinical studies will explore additional questions, such as whether four times a day dosing is less effective than six times a day dosing in the treatment of stromal fibrosis.

Histopathologic effects of mobile phone radiation exposure on the testes and sperm parameters: a systematic literature review of animal studies

Histopathologic effects of mobile phone radiation exposure on the testes and sperm parameters: a systematic literature review of animal studies

Fetal Safety in MRI During Pregnancy: A Comprehensive Review.

As medical imaging continues to expand, concerns about the potential risks of ionizing radiation to the developing fetus have led to a preference for non-radiation-based alternatives such as ultrasonography and fetal MRI. This review examines the current evidence on the safety of MRI during pregnancy, with a focus on 3 T MRI and contrast agents, aiming to provide a comprehensive synthesis that informs clinical decision-making, ensures fetal safety and supports the safe use of all available modalities that could impact management. We conducted a comprehensive review of studies from 2000 to 2024 on MRI safety during pregnancy, focusing on 3 T MRI and gadolinium use. The review included peer-reviewed articles and large database studies, summarizing key findings and identifying areas for further research. Fetal MRI, used alongside ultrasound, enhances diagnostic accuracy for fetal anomalies, particularly in the brain, thorax, gastrointestinal and genitourinary systems, with no conclusive evidence of adverse effects on fetal development. While theoretical risks such as tissue heating and acoustic damage exist, studies show no significant harm at 1.5 T or 3 T, though caution is still advised in the first trimester. Regarding gadolinium-based contrast agents, the evidence is conflicting: while some studies suggest risks such as stillbirth and rheumatological conditions, animal studies show minimal fetal retention and no significant toxicity, and later clinical research has not substantiated these risks. The existing literature on fetal MRI is encouraging, suggesting minimal risks; however, further investigation through larger, prospective and long-term follow-up studies is essential to comprehensively determine its safety and late effects.

Basic research for ultrasound-guided injection into skeletal muscle lesions in an experimental animal model.

Ultrasound-guided injection techniques are expected to enhance therapeutic efficacy for skeletal muscle injuries and disorders, but basic knowledge is lacking. The purpose of this study was to examine the diagnostic accuracy of ultrasound for abnormal skeletal muscle lesions, and to examine the distribution patterns of solution and cells injected into abnormal muscle lesions under ultrasound guidance. A cardiotoxin (CTX)-induced muscle injury model was used. Briefly, CTX was injected into tibialis anterior muscle in rats under ultrasound observation. First, the diagnostic accuracy of abnormal muscle lesions on ultrasound was examined by comparing ultrasound findings and histology. Next, Fast Green solution and green fluorescent protein (GFP)-labelled cells were simultaneously injected into the abnormal muscle lesions under ultrasound guidance, and their distribution was evaluated. Evaluation of short-axis ultrasound images and cross-sectional histological staining showed a strong correlation (r = 0.927; p < 0.001) between the maximum muscle damage area in ultrasound and haematoxylin and eosin (H&E) staining evaluations. Histological analysis showed that ultrasound-guided injection could successfully deliver Fast Green solution around the myofibres at the site of injury. In contrast, the distribution of injected cells was very localized compared to the area stained with Fast Green. This experimental animal study demonstrated the potential of ultrasound to quantitatively visualize abnormalities of skeletal muscle. It also showed that ultrasound-guided injections allowed for highly accurate distribution of solution and cells in abnormal muscle tissue, but the patterns of solution and cell distribution were markedly different. Although future studies using a more clinically relevant model are necessary, these results are important findings when considering biological therapies for skeletal muscle injuries and disorders.

Photoprotective Effects of Phytochemicals on Blue Light-Induced Retinal Damage: Current Evidence and Future Perspectives.

The widespread use of light-emitting diodes (LEDs) has increased blue light (BL) exposure, raising concerns about its potential adverse effects on ocular health. Prolonged exposure to BL has been implicated in the pathogenesis of various retinal disorders, including age-related macular degeneration (AMD), primarily through mechanisms involving oxidative stress and inflammation mediated by the overproduction of reactive oxygen species (ROS). This review synthesizes current evidence on the photoprotective properties of dietary bioactive compounds, (e.g., anthocyanins, curcumin, quercetin, myricetin, and resveratrol), with a focus on their potential to mitigate BL-induced retinal damage. Accumulating research suggests that dietary antioxidants, particularly polyphenols, may offer photoprotective benefits. These phytochemicals act by neutralizing ROS and enhancing the retina's endogenous antioxidant capacity. Based on these findings, this review advocates for a food-first approach in future investigations, emphasizing the development of evidence-based dietary recommendations to bolster retinal health and mitigate the risk of BL-related ocular diseases. Considering the current lack of empirical clinical studies examining the impact of BL on human ocular health, future research in the field of BL hazard should prioritize two key approaches: conducting large-scale epidemiological dietary surveys and implementing clinical trials on functional ingredients that have demonstrated beneficial effects against photodamage in preclinical animal studies.

Anticancer effect of the antirheumatic drug leflunomide on oral squamous cell carcinoma by the inhibition of tumor angiogenesis

ObjectivesLeflunomide (LEF) is a conventional synthetic disease-modifying antirheumatic drug and suppresses T-cell proliferation and activity by inhibiting pyrimidine synthesis using dihydroorotase dehydrogenase (DHODH); however, several studies have demonstrated that LEF possesses anticancer and antiangiogenic effects in some malignant tumors. Therefore, we investigated the anticancer and antiangiogenic effects of LEF on oral squamous cell carcinoma (OSCC).MethodsTo evaluate the inhibitory effect of LEF on OSCC, cell proliferation and wound-healing assays using human OSCC cell lines were performed. The DHODH inhibitory effect of LEF was evaluated by Western blot. To assess the suppression of pyrimidine biosynthesis induced by LEF on OSCC, cell proliferation assays with or without uridine supplementation were performed. The antiangiogenic effect of LEF was evaluated by in vitro tube formation assay using immortalized human umbilical vein endothelial cells, which were electroporatically transfected with hTERT. The tumor-suppressive effect of LEF in vivo was examined in both immunodeficient and syngeneic mice by implanting mouse OSCC cells. Tumor vascularization was evaluated by immunohistochemistry of the tumor extracted from syngeneic mice.ResultsLEF dose-dependently inhibited OSCC proliferation and migration. LEF significantly inhibited DHODH expression, and uridine supplementation rescued the inhibitory effect of LEF. LEF dose-dependently suppressed endothelial tube formation. In the animal study, LEF significantly suppressed tumor growth in both immunodeficient and syngeneic mice. Histologically, LEF decreased DHODH expression and tumor vascularization.ConclusionLEF is a potent anticancer agent with antiangiogenic effects on OSCC and might be clinically applicable to OSCC by drug repositioning.

Low dose DNA methyltransferase inhibitors potentiate PARP inhibitors in homologous recombination repair deficient tumors

BackgroundPoly (ADP-Ribose) polymerase inhibitors are approved for treatment of tumors with BRCA1/2 and other homologous recombination repair (HRR) mutations. However, clinical responses are often not durable and treatment may be detrimental in advanced cancer due to excessive toxicities. Thus we are seeking alternative therapeutics to enhance PARP-directed outcomes. In an effort to expand the clinical use of PARP inhibitors to HRR proficient tumors, several groups have tested combinations of DNA methyltransferase inhibitors and PARP inhibitors. While this approach attenuated tumor cell proliferation in preclinical studies, subsequent clinical trials revealed little benefit. We hypothesized that benefit for this drug combination would only be specific to HRR deficient tumors, due to their inability to enact high fidelity DNA repair with subsequent cell death.MethodsWe generated hypomorphic BRCA1 and BRCA2 variants of the HRR proficient triple negative breast cancer cell line MDA-MB-231. We compared therapeutic response features such as RAD51 focus formation, cell cycle fraction alterations, DNA damage accumulation, colony formation, and cell death of these and other cell lines with and without intrinsic BRCA1/2 mutations. Results were confirmed in BRCA1/2 intact and deficient xenografts and PDX.ResultsOur targeted variants and cells with intrinsic BRCA1/2 mutations responded to low dose combination therapeutic treatment by G2M stalling, compounded DNA damage, severely attenuated colony formation, and importantly, increased cell death. In contrast, the parental MDA-MB-231 cells and other HRR proficient cell lines produced smaller cell populations with short term treatment, but with much less cumulative DNA damage, and minimal cell death. In animal studies, our BRCA-engineered hypomorphs and several independent PDX models with clinically relevant BRCA mutations were acutely more vulnerable to this drug combination.ConclusionsWe conclude that low dose DNA methyltransferase inhibition can cooperate with low dose PARP inhibition to increase DNA damage predominantly in cells with HRR deficiencies, ultimately producing more cell death than in HRR proficient tumors. We predict that clinical benefit will more likely be apparent in patients with DNA repair defective tumors and are focusing clinical exploration of this drug combination in these patients, with the goals of enhancing tumor cell death at minimal toxicities.

MOF-derived intelligent arenobufagin nanocomposites with glucose metabolism inhibition for enhanced bioenergetic therapy and integrated photothermal-chemodynamic-chemotherapy

Bioenergetic therapy based on tumor glucose metabolism is emerging as a promising therapeutic modality. To overcome the poor bioavailability and toxicity of arenobufagin (ArBu), a MOF-derived intelligent nanosystem, ZIAMH, was designed to facilitate energy deprivation by simultaneous interventions of glycolysis, OXPHOS and TCA cycle. Herein, zeolitic imidazolate framework-8 was loaded with ArBu and indocyanine green, encapsulated within metal–phenolic networks for chemodynamic therapy and hyaluronic acid modification for tumor targeting. ZIAMH nanoparticles can release ArBu in the tumor microenvironment for chemtherapy, and ICG enables photothermal therapy under near-infrared laser irradiation. In vitro and in vivo mechanism studies revealed that the ZIAMH nanoplatform downregulated glucose metabolism related genes, resulting in the reduction of energy substances and metabolites in tumors. Additionally, it significantly promoted cell apoptosis by upregulating pro-apoptotic proteins such as Bax, Bax/Bcl-2, cytochrome C. Animal studies have shown that the tumor inhibition efficiency of ZIAMH nanomedicines was three fold higher than that of free drugs. Therefore, this study provides a new strategy for glucose metabolism-mediated bioenergetic therapy and PTT/CDT/CT combined therapy for tumors.Graphical

Novel Approach to Vascular Thymic Tissue Transplantation in Humans: A Case Report.

Vascular thymus transplantation has been explored in animal models but remains untested in humans. Current approaches to congenital athymia involve avascular transplantation of allogeneic thymic tissue, which may delay immune recovery. Building on animal studies, we propose revascularization of thymic tissue in a human model. This case report details about the revascularization of neonatal thymic tissue in an elderly woman with terminal cancer, evaluating revascularization efficacy, rejection risks, and procedural safety over a 3-week period. A thymic tissue graft obtained from a neonate during corrective heart surgery was implanted into the left radial forearm of an 85-year-old woman. The graft was evaluated for 3 weeks, with one thymic vein anastomosed to the cephalic vein and one thymic artery to the radial artery. No immunosuppression or HLA matching was employed. Weekly Doppler ultrasound and postexplantation histopathology monitored blood flow and graft status. Hematologic, biochemical, radiological evaluations, and daily clinical follow-up were conducted. This preliminary research demonstrates the feasibility of revascularizing a neonatal thymus in an adult using microsurgical techniques.

The effect of light-emitting diode-mediated photobiomodulation therapy on orthodontic tooth movement: A literature review.

This study aims to review and analyze the impact of light-emitting diode (LED) photobiomodulation (PBM) therapy on orthodontic tooth movement. This non-invasive technique is proposed to reduce time-related side effects, such as white spot lesions, dental caries, and root resorption. Five studies were included in the review, comprising two animal studies (ages 10 and 12 weeks) and three human studies (ages ranging from 15 to 17 years). All studies applied PBM concurrently with force application using sliding mechanics for canine retraction (three studies) and molar protraction (two studies). Two studies employed LEDs with a wavelength of 850 nm, with an exposure time of 5 minutes daily. Another two studies used LEDs with a wavelength of 618 nm, with an exposure time of 20 minutes daily. In summary, these studies demonstrated that LED-mediated PBM enhanced orthodontic tooth movement by 33% (a 1.36-fold increase) compared to the control group. The mean tooth movement per month was 1.55 ± 0.33 mm, which was higher than the control group's average of 1.06 ± 0.35 mm. Also, no studies demonstrated any side effects such as anchorage loss, root resorption, canine rotation, or tooth inclinations. In conclusion, LED-mediated PBM (at wavelengths of 618 nm and 850 nm) can accelerate orthodontic tooth movement without adverse effects, thanks to its biostimulatory properties. Given the advantages of LEDs over traditional lasers-particularly their lower cost and easier application-this method shows promise as a tool to accelerate tooth movement, potentially reducing treatment time and associated side effects.

Differences of microbial growth and biofilm formation among periprosthetic joint infection-causing species: an animal study.

The most frequently used surgical procedures for periprosthetic joint infections (PJIs) are debridement, antibiotics, and implant retention (DAIR), as well as single- or two-stage revision arthroplasty. The choice of surgery is made depending on the full maturation of the biofilm layer. The purpose of this study was to evaluate the biofilm formation and microbial growth using common PJI-causing agents and compare its development on the implant surface. The in vivo study was performed using 40 Sprague-Dawley rats divided into five groups (n = 8/group): Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Candida albicans, and control. Six standard titanium alloy discs were placed into the subcutaneous air pouches of the interscapular areas of the rats. After the inoculation of microorganisms, disc and soft tissue cultures were collected at 2-week intervals for 6weeks, and the microbial load and the microscopic appearance of the biofilm were compared. The disc samples from the S. aureus group had the highest infection load at all time points; however, in soft tissue samples, this was only observed at week 4 and 6. Electron microscopic images showed no distinctive differences in the biofilm structures between the groups. S. aureus microbial burden was significantly higher in implant cultures at week 2 compared to other PJI-causing agents examined. These results may explain the higher failure rate seen if the DAIR procedure was performed at < 3-4weeks after the PJI symptom onset and support the observation that DAIR may not be effective against PJIs caused by S. aureus.

Impact of microplastics on female reproductive health: insights from animal and human experimental studies: a systematic review.

This systematic review aims to evaluate the impact of microplastics on female reproductive health by analyzing experimental studies. A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases to identify experimental studies published between 2021 and 2023. Studies investigating the effects of microplastics on reproductive organs, hormone levels, fertility rates, and offspring development in female subjects were included. The quality of the studies was assessed using the Cochrane risk of bias tool. A total of 15 studies met the inclusion criteria. The results indicate that exposure to microplastics significantly affects ovarian function, decreases fertility rates, and disrupts hormone levels in female subjects. Several studies also reported negative effects on embryo development and offsprings health. The quality of the studies varied, with some showing a high risk of bias. The evidence from experimental studies suggests that microplastics have a detrimental effect on female reproductive health. However, the variation in study quality highlights the need for more rigorous research to confirm these results and better understand the underlying mechanisms.

Neural Stem/Progenitor Cell Therapy in Patients and Animals with Amyotrophic Lateral Sclerosis: A Systematic Review and Meta-analysis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative malady that causes progressive degeneration and loss of motor neuron function in the brain and spinal cord, eventually resulting in muscular atrophy, paralysis, and death. Neural stem/progenitor cell (NSPC) transplantation can improve bodily function in animals and delay disease progression in patients with ALS. This paper summarizes and analyzes the efficacy and safety of neural stem/progenitor cell (NSPC) transplantation as a treatment for ALS, aiming to improve function and delay disease progression in patients. We present a summary of the pathogenic mechanism and causative genes associated with ALS and describe the mechanism and efficacy of NSPC treatment for ALS. We comprehensively searched for relevant English-language articles published between January 1, 2000 and October 1, 2023, across the following five medical databases: PubMed, EMBASE, OVID, Web of Science, and the Cochrane Library. We examined experimental indices of physical function in animals and patients who underwent stem cell transplantation. All statistical analyses were performed via Review Manager 5.4. The study comprised a total of 16 investigations, including 5 clinical studies and 11 animal studies and involving 66 patients and 203 animals. The meta-analysis revealed that the administration of NSPCs appeared to yield positive outcomes in clinical patients, as assessed by the ALS functional rating scale and forced vital capacity. Furthermore, improvements following cell injection were observed in the rotarod test results, the Basso-Beattie-Bresnahan Locomotor Rating Scale score, weight, and survival time. Our meta-analysis, which was grounded in randomized controlled trials, revealed that the transplantation of neural stem/progenitor cells (NSPCs), has potential effects on ALS patients, enhancing the physical function of animals and mitigating degenerative effects in individuals. These underscored the promise of NSPC therapy as a viable treatment option. We report that the transplantation of neural stem/progenitor cells (NSPCs) is promising for enhancing bodily function and slowing the progression of ALS in affected patients. In this review, we summarize the treatment of ALS with NSPCs, evaluating both its efficacy and safety. Through database searches, we identified 16 studies involving 66 patients and 203 animals and analyzed the experimental indices of physical function following stem cell transplantation. The meta-analysis results indicated a positive impact of NSPCs on the clinical conditions of patients and the behavior of animals. A meta-analysis of randomized controlled trials further supported the conclusion that NSPC transplantation has a beneficial effect on improving physical function and mitigating degeneration in ALS patients.

Intentions in interactions: an enactive reply to expressive communication proposals

The search for origins of human linguistic behavior is a consuming project in many fields. Philosophers drawing on studies of animal behavior are working to revise some of the standard cognitive requirements in hopes of linking the origins of human language to non-human animal communication. This work depends on updates to Grice’s theory of communicative intention and Millikan’s teleosemantics. Yet the classic idea of speaker meaning on which these new projects rest presupposes coherent, stable, individual, internal, and prior intention as a cognitive or mental state, which is also the framework presupposed in theory of mind. This framework neglects the co-authored nature of communicative intentions and is thereby at odds with enactivist views of cognition. In this paper we draw on the idea of participatory sense-making alongside research on non-human animal communication to identify utterances—co-authored meaningful acts—as the token of communicative activity cross-species. Utterances by our definition are expressive, relational, and work without mindreading. In closing we propose the possibility of dialogical subjectivity, and engage with animal studies to show that some species exhibit its traits.

Unveiling the Emerging Role of Xanthine Oxidase in Acute Pancreatitis: Beyond Reactive Oxygen Species.

Acute pancreatitis (AP) is a potentially fatal acute digestive disease that is widespread globally. Although significant progress has been made in the previous decade, the study of mechanisms and therapeutic strategies is still far from being completed. Xanthine oxidase (XO) is an enzyme that catalyzes hypoxanthine and xanthine to produce urate and is accompanied by the generation of reactive oxygen species (ROS) in purine catabolism. Considerable preclinical and clinical studies have been conducted over many decades to investigate the role of XO in the pathogenesis of AP and its potential targeting therapeutic value. There is no doubt that the ROS generated by irreversibly activated XO participates in the local pancreas and multiple organ failure during AP. However, the optimal timing and doses for therapeutic interventions targeting XO in animal studies and the clinic, as well as the additional molecular mechanisms through which XO contributes to disease onset and progression, including metabolic regulation, remain to be elucidated. This review summarized the benefits and contradictions of using XO inhibitors in animal models, offered mechanisms other than ROS, and discussed the difficulties faced in clinical trials. We hope to provide a perspective on the future worthwhile basic and clinical research on XO by analyzing its chemical and biological characteristics, as well as the progress of its regulatory mechanisms in AP.

Genome-Wide Screening in Haploid Stem Cells Reveals Synthetic Lethality Targeting MLH1 and TP53 Deficient Tumours.

Synthetic lethality is defined as a type of genetic interaction where the combination of two genetic events results in cell death, whereas each of them separately does not. Synthetic lethality can be a useful tool in personalised oncology. MLH1 is a cancer-related gene that has a central role in DNA mismatch-repair and TP53 is the most frequently mutated gene in cancer. To identify genetic events that can lead to tumour death once either MLH1 or TP53 is mutated, a genome-wide genetic screening was performed. Thus, mutations in all protein-coding genes were introduced into haploid human embryonic stem cells (hESCs) with and without loss-of-function mutations in the MLH1 or TP53 genes. These experiments uncovered a list of putative hits with EXO1, NR5A2, and PLK2 genes for MLH1, and MYH10 gene for TP53 emerging as the most promising candidates. Synthetic lethal interactions of these genes were validated genetically or chemically using small molecules that inhibit these genes. The specific effects of SR1848, which inhibits NR5A2, ON1231320 or BI2536, which inhibits PLK2, and blebbistatin, which inhibits MYH10, were further validated in cancer cell lines. Finally, animal studies with CCL xenografts showed the selective effect of the small molecule BI2536 on MLH1-null tumours and of blebbistatin on TP53-mutated tumours. Thus, demonstrating their potential for personalised medicine, and the robustness of genetic screening in haploid hESCs in the context of cancer therapeutics.

The role of beta band phase resetting in audio-visual temporal order judgment

The integration of auditory and visual stimuli is essential for effective language processing and social perception. The present study aimed to elucidate the mechanisms underlying audio-visual (A-V) integration by investigating the temporal dynamics of multisensory regions in the human brain. Specifically, we evaluated inter-trial coherence (ITC), a neural index indicative of phase resetting, through scalp electroencephalography (EEG) while participants performed a temporal-order judgment task that involved auditory (beep, A) and visual (flash, V) stimuli. The results indicated that ITC phase resetting was greater for bimodal (A + V) stimuli compared to unimodal (A or V) stimuli in the posterior temporal region, which resembled the responses of A-V multisensory neurons reported in animal studies. Furthermore, the ITC got lager as the stimulus-onset asynchrony (SOA) between beep and flash approached 0 ms. This enhancement in ITC was most clearly seen in the beta band (13–30 Hz). Overall, these findings highlight the importance of beta rhythm activity in the posterior temporal cortex for the detection of synchronous audiovisual stimuli, as assessed through temporal order judgment tasks.