Mitochondrial respiratory complex III sustains IL-10 production in activated macrophages and promotes tumor-mediated immune evasion.

The cytokine interleukin-10 (IL-10) limits the immune response and promotes resolution of acute inflammation. Because of its immunosuppressive effects, IL-10 up-regulation is a common feature of tumor progression and metastasis. Recently, IL-10 regulation has been shown to depend on mitochondria and redox-sensitive signals.

The deubiquitinase USP5 prevents accumulation of protein aggregates in cardiomyocytes.

Protein homeostasis is crucial for maintaining cardiomyocyte (CM) function. Disruption of proteostasis results in accumulation of protein aggregates causing cardiac pathologies such as hypertrophy, dilated cardiomyopathy (DCM), and heart failure. Here, we identify ubiquitin-specific peptidase 5 (USP5) as a critical determinant of protein quality control (PQC) in CM.

Noncanonical role of Golgi-associated macrophage TAZ in chronic inflammation and tumorigenesis.

Until now, Hippo pathway-mediated nucleocytoplasmic translocation has been considered the primary mechanism by which yes-associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) transcriptional coactivators regulate cell proliferation and differentiation via transcriptional enhanced associate domain (TEAD)-mediated target gene expression. In this study, however, we found that TAZ, but not YAP, is associated with the Golgi apparatus in macrophages activated via Toll-like receptor ligands during the resolution phase of inflammation. Golgi-associated TAZ enhanced vesicle trafficking and secretion of proinflammatory cytokines in M1 macrophage independent of the Hippo pathway.

Cardiac allograft tolerance can be achieved in nonhuman primates by donor bone marrow and kidney cotransplantation.

Long-term, immunosuppression-free allograft survival has been induced in human and nonhuman primate (NHP) kidney recipients after nonmyeloablative conditioning and donor bone marrow transplantation (DBMT), resulting in transient mixed hematopoietic chimerism. However, the same strategy has consistently failed in NHP heart transplant recipients. Here, we investigated whether long-term heart allograft survival could be achieved by cotransplanting kidneys from the same donor.

Amyloid-associated hyperconnectivity drives tau spread across connected brain regions in Alzheimer's disease.

In Alzheimer's disease (AD), amyloid-β (Aβ) triggers the aggregation and spreading of tau pathology, which drives neurodegeneration and cognitive decline. However, the pathophysiological link between Aβ and tau remains unclear, which hinders therapeutic efforts to attenuate Aβ-related tau accumulation. Aβ has been found to trigger neuronal hyperactivity and hyperconnectivity, and preclinical research has shown that tau spreads across connected neurons in an activity-dependent manner.

Triple knockdown of , , and in T cells reduces CAR-T cell toxicity but preserves activity against solid tumors in mice.

Chimeric antigen receptor (CAR)-T cell therapies have revolutionized the landscape of cancer treatment, in particular in the context of hematologic malignancies. However, for solid tumors that lack tumor-specific antigens, CAR-T cells can infiltrate and attack nonmalignant tissues expressing the CAR target antigen, leading to on-target, off-tumor toxicity. Severe on-target, off-tumor toxicities have been observed in clinical trials of CAR-T therapy for solid tumors, highlighting the need to address this issue.

Perinatal dysfunction of innate immunity in cystic fibrosis.

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF.

Expanding the Genetic Etiology of Multiple Morphological Abnormalities of the Sperm Flagella: A Case Report of Two Novel DNAH1 Variants.

Background: The following case report details the genetic evaluation and treatment of a 30-year-old male with a history of asthenoteratospermia and notable abnormalities of the sperm flagella.

Methods: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.

Results: Genetic evaluation was performed via a multi-gene panel of genes associated with primary ciliary dyskinesia and multiple morphological abnormalities of the sperm flagella (MMAF) prior to the couple's in vitro fertilization (IVF) cycle.

A pan-orthohantavirus human lung xenograft mouse model and its utility for preclinical studies.

Orthohantaviruses are emerging zoonotic viruses that can infect humans via the respiratory tract. There is an unmet need for an in vivo model to study infection of different orthohantaviruses in physiologically relevant tissue and to assess the efficacy of novel pan-orthohantavirus countermeasures. Here, we describe the use of a human lung xenograft mouse model to study the permissiveness for different orthohantavirus species and to assess its utility for preclinical testing of therapeutics.

Topical application of the ethanol extract and the hydroethanolic fraction of ripe Solanum lycocarpum A. St. Hil. fruit improves the healing of excisional wounds.

Purpose: To evaluate the effect of the topical application of the ethanol extract (EESL) and the hydroethanolic fraction (HFSL) of ripe Solanum lycocarpum fruit on the healing of experimentally-induced wounds in mice.

Methods: The EESL and HFSL obtained from ripe fruit of the species S. lycocarpum were obtained by percolation with ethanol.

CHROMOPHOBE HEPATOCELLULAR CARCINOMA: DIAGNOSTIC CHALLENGES.

Background: Hepatocellular carcinoma (HCC) encompasses rare variants like chromophobe hepatocellular carcinoma (CHCC) characterized by distinct histological features and molecular profiles.

Case Report: A 56-year-old male with chronic hepatitis C, presenting pain in the right hypochondrium. Imaging revealed a solitary liver lesion, subsequently resected and histologically diagnosed as HCC.

SURGICAL TECHNIQUES TO INCREASE RESECTABILITY IN LIVER METASTASIS.

The development of surgical techniques, chemotherapy, biological agents, and multidisciplinary approaches have made patients with unresectable colorectal liver metastases eligible for surgery. Many strategies have been developed to allow patients for surgical resection (percutaneous portal vein embolization, liver venous deprivation, parenchyma-sparing liver surgery, reverse strategy, associating liver partition and portal vein ligation for staged hepatectomy, and liver transplantation), the only form of disease control and curative treatment.

MANAGEMENT OF SYNCHRONIC LARGE LIVER METASTASIS IN A NON-OCCLUSIVE COLON TUMOR.

In patients with synchronic liver colorectal metastasis, resection of the primary tumor and liver metastases is the only potentially curative strategy. In such cases, there is no consensus on whether resection of the primary tumor and metastases should be performed simultaneously or whether a staged approach should be performed (resection of the primary tumor and after, hepatectomy, or hepatectomy first). Patients with no bowel occlusion and with extensive liver disease are advised neoadjuvant oncological therapy.

NON-FUNCTIONING SPORADIC PANCREATIC NEUROENDOCRINE TUMOR IS AN INDEPENDENT RISK FACTOR FOR RECURRENCE AFTER SURGICAL TREATMENT.

Background: Pancreatic neuroendocrine tumors (PNETs) are uncommon and heterogeneous neoplasms, often exhibiting indolent biological behavior. Their incidence is rising, largely due to the widespread use of high-resolution imaging techniques, particularly influencing the diagnosis of sporadic non-functioning tumors, which account for up to 80% of cases. While surgical resection remains the only curative option, the impact of factors such as tumor grade, size, and type on prognosis and recurrence is still unclear.

Growth and metabolic functions of Schizolobium amazonicum subjected to nickel doses.

Anthropic activities such as industries, agriculture and mining has generated public concern for its numerous irregular disposals of its waste, the incorrect deposition of heavy metals such as nickel (Ni) has caused the degradation and contamination of groundwater and water. Studies that point out cheap and efficient solutions have been an obstacle to the advancement of solutions for degraded area recovery programs. For this, a vegetable home experiment was developed, with an entirely randomized design with 5 treatments being a control (no metal) and 4 nickel concentrations (200 μM/L; 400 μM/L; 600 μM/L and 800 μM/L) with 6 repetitions.

Physical development and sociocultural context influences on children's physical activity.

Objective: To examine the predictive strength of cardiorespiratory fitness (CRF), motor competence (MC), maternal educational status, and parental perception of their children's favorite leisure activities for meeting physical activity (PA) guidelines of each gender among children aged 3-6 years.

Methods: This is a cross-sectional study with 367 preschoolers (53% girls), assessing CRF (PREFIT 20m shuttle run), MC (battery of motor skills), PA (accelerometry), maternal education and parental perception of children's preferred leisure (questionnaires). Factorial analysis of covariance, multiple logistic regression, and chi-square tests were conducted.

Therapeutic strategies for tongue musculature: a systematic literature review.

Purpose: To analyze the different therapeutic strategies prescribed in orofunctional rehabilitation of the tongue musculature.

Research Strategies: Regional Portal of the Virtual Health Library for Latin America and the Caribbean, Embase, PubMed/MEDLINE, Scientific Electronic Library Online, SciVerse Scopus and Cochrane databases were consulted, with the descriptors "exercise therapy" OR "physiology" OR "musculoskeletal physiological phenomena" OR "digestive system and oral physiological phenomena" AND "speech therapy" OR "myofunctional therapy" OR "speech language pathology" AND "tongue". Studies indexed until October 5, 2023, were included.

Hepatitis B infection (HBsAg and HBeAg) status among women attending antenatal care at public healthcare facilities of South Africa, 2017.

Eight years after WHO adopted a resolution to eliminate hepatitis B by the year 2030, the disease remains a global public health concern, with vertical transmission of HBV being a major obstacle to this goal. Our study aimed to determine the HBV infection status of pregnant women in South Africa at a national level to evaluate the risk of vertical transmission and provide evidence for public health decision-making. We conducted HBsAg testing on 1,942 HIV-uninfected and 2,312 HIV-infected pregnant women from South Africa's public health sector in 2017, followed by HBeAg testing on HBsAg-positive samples.

Effects of stimuli and contralateral noise levels on auditory cortical potentials recorded in school-age children.

Background And Objective: One of the functions attributed to the auditory efferent system is related to the processing of acoustic stimuli in noise backgrounds. However, clinical implications and the neurophysiological mechanisms of this system are not yet understood, especially on higher regions of the central nervous system. Only a few researchers studied the effects of noise on cortical auditory evoked potentials (CAEP), but the lack of studies in this area and the contradictory results, especially in children, point to the need to investigate different protocols and parameters that could allow the study of top-down activity in humans.

Exploring Glypican-3 targeted CAR-NK treatment and potential therapy resistance in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most prevalent form of primary liver cancer and the second leading cause of cancer-related mortality globally. Despite advancements in current HCC treatment, it remains a malignancy with poor prognosis. Therefore, developing novel treatment options for patients with HCC is urgently needed.

Hypopigmented mycosis fungoides: an important differential diagnosis of hypochromias in childhood.

Objective: To highlight the importance of early recognition of hypopigmented mycosis fungoides (HMF) in cases of cutaneous hypochromia in children, with a view to an effective diagnostic and therapeutic approach.

Case Description: Two cases of HMF in children are reported. The first case involves an eight-year-old boy with hypochromic macules on the trunk and root of the upper and lower limbs, while the second case is a six-year-old boy with widespread hypochromic patches.

Congenital toxoplasmosis in infants from chronically infected mothers: report of two cases.

Objective: To describe two severe cases of congenital toxoplasmosis in infants born to chronically infected mothers who did not receive education or information on the prevention of gestational toxoplasmosis during prenatal care.

Case Description: The mothers had a previous serological diagnosis of toxoplasmosis conducted during prenatal care, with non-reactive (<10 IU/mL) IgM and reactive IgG (>10 IU/mL), and were considered "immune" to the infection. Both infants were born with sequelae of the congenital infection, including neurological and ocular alterations.

GsMTx-4 combined with exercise improves skeletal muscle structure and motor function in rats with spinal cord injury.

Motor dysfunction and muscle atrophy are typical symptoms of patients with spinal cord injury (SCI). Exercise training is a conventional physical therapy after SCI, but exercise intervention alone may have limited efficacy in reducing secondary injury and promoting nerve regeneration and functional remodeling. Our previous research found that intramedullary pressure after SCI is one of the key factors affecting functional prognosis.

Protect or prevent? A practicable framework for the dilemmas of COVID-19 vaccine prioritization.

Determining COVID-19 vaccination strategies presents many challenges in light of limited vaccination capacity and the heterogeneity of affected communities. Who should be prioritized for early vaccination when different groups manifest different levels of risks and contact rates? Answering such questions often becomes computationally intractable given that network size can exceed millions. We obtain a framework to compute the optimal vaccination strategy within seconds to minutes from among all strategies, including highly dynamic ones that adjust vaccine allocation as often as required, and even with modest computation resources.

In vivo mapping of sodium homeostasis disturbances in individual ALS patients: A brain 23Na MRI study.

Objective: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by significant heterogeneity among patients. 23Na MRI maps abnormal sodium homeostasis that reflects metabolic alterations and energetic failure contributing to the neurodegenerative process. In this study, we investigated disease severity at the individual level in ALS patients using brain 23Na MRI.