Positive selection in gamete interaction proteins in Carnivora.

The absence of robust interspecific isolation barriers among pantherines, including the iconic South American jaguar (Panthera onca), led us to study molecular evolution of typically rapidly evolving reproductive proteins within this subfamily and related groups. In this study, we delved into the evolutionary forces acting on the zona pellucida (ZP) gamete interaction protein family and the sperm-oocyte fusion protein pair IZUMO1-JUNO across the Carnivora order, distinguishing between Caniformia and Feliformia suborders and anticipating few significant diversifying changes in the Pantherinae subfamily. A chromosome-resolved jaguar genome assembly facilitated coding sequences, enabling the reconstruction of protein evolutionary histories. Examining sequence variability across more than 30 Carnivora species revealed that Feliformia exhibited significantly lower diversity compared to its sister taxa, Caniformia. Molecular evolution analyses of ZP2 and ZP3, subunits directly involved in sperm-recognition, unveiled diversifying positive selection in Feliformia, Caniformia and Pantherinae, although no significant changes were linked to sperm binding. Structural cross-linking ZP subunits, ZP4 and ZP1 exhibited lower levels or complete absence of positive selection. Notably, the fusion protein IZUMO1 displayed prominent positive selection signatures and sites in basal lineages of both Caniformia and Feliformia, extending along the Caniformia subtree but absent in Pantherinae. Conversely, JUNO did not exhibit any positive selection signatures across tested lineages and clades. Eight Caniformia-specific positive selected sites in IZUMO1 were detected within two JUNO-interaction clusters. Our findings provide for the first time insights into the evolutionary trajectories of ZP proteins and the IZUMO1-JUNO gamete interaction pair within the Carnivora order.

Novel Zn(II)-complex with hybrid chalcone-thiosemicarbazone ligand: Synthesis, characterization, and inhibitory effect on HTLV-1-infected MT-2 leukemia cells.

Chalcone and thiosemicarbazone have attracted attention due to their easy synthetic procedure and high success in the development of antiviral and antitumor, however, there are few biological data on the evaluation of chalcone-thiosemicarbazone hybrids and their complexation with metal ions. In this sense, the present work reports the synthesis and characterization of the hybrid (Z)-2-((E)-3-(4-chlorophenyl)-1-phenylallylidene)hydrazine-1-carbothioamide (CTCl) and its Zn(II)-complex (CTCl-Zn). The compounds were cell-based evaluated in terms of cytotoxicity against human T-cell lymphotropic virus type 1 (HTLV-1) infected leukemia cells (MT-2) and the experimental data were correlated with molecular docking calculations. The ligand and Zn(II)-complex were easily synthesized with a good yield - 57% and 79%, respectively. The dynamic of E/Z isomers with respect to the imine bond configuration of CTCl was evidenced by 1H NMR experiments in DMSO­d6, while the X-ray diffraction of CTCl-Zn showed that Zn(II) ion is tetracoordinated to two ligands in a bidentate mode and the metal ion lies on an intermediate geometry between the see-saw and trigonal pyramid. The ligand and complex exhibited low toxicity and the Zn(II)-complex is more cytotoxic than the ligand, with the corresponding IC50 value of 30.01 and 47.06 µM. Both compounds had a pro-apoptotic effect without the release of reactive oxygen species (ROS) and they can interact with DNA via minor grooves driven by van der Waals forces.

Clinical and molecular overview of immunotherapeutic approaches for malignant skin melanoma: Past, present and future.

Traditional therapeutic approaches for malignant melanoma, have proved to be limited and/or ineffective, especially with respect to their role in improving patient survival and tumor recurrence. In this regard, immunotherapy has been demonstrated to be a promising therapeutic alternative, boosting antitumor responses through the modulation of cell signaling pathways involved in the effector mechanisms of the immune system, particularly, the so-called "immunological checkpoints". Clinical studies on the efficacy and safety of immunotherapeutic regimens, alone or in combination with other antitumor approaches, have increased dramatically in recent decades, with very encouraging results. Hence, this review will discuss the current immunotherapeutic regimens used to treat malignant melanoma, as well as the molecular and cellular mechanisms involved. In addition, current clinical studies that have investigated the use, efficacy, and adverse events of immunotherapy in melanoma will also be discussed.

Spontaneous ovarian hyperstimulation syndrome in a pregnant woman with hypothyroidism: a case report.

OBJECTIVE: To study a rare case of spontaneous ovarian hyperstimulation syndrome in a naturally conceived pregnancy associated with overt hypothyroidism. DESIGN: Case report. SETTING: Endocrinology private practice. PATIENTS: A 32-year-old woman who was 13 weeks pregnant with bilaterally enlarged ovaries presumed to be secondary to hypothyroidism. INTERVENTIONS: Administration of levothyroxine and titration of the dose. MAIN OUTCOME MEASURES: Regression of signs and symptoms of spontaneous ovarian hyperstimulation syndrome after 12 weeks of therapy. RESULTS: The patient was diagnosed with severe hypothyroidism, as confirmed by her elevated thyroid-stimulating hormone level. Ultrasound evaluation revealed ovarian enlargement secondary to multiple contiguous cysts with anechoic content. The patient was administered levothyroxine 175 µg/day. Results of hormonal studies demonstrated thyroid function normality at week 12 after treatment. Incomplete regression of ovarian cysts was also noticed within this period. At week 37, the patient developed preeclampsia, and cesarean delivery was recommended. An 8-month postpartum ultrasound evaluation revealed complete regression of the cysts. CONCLUSIONS: Spontaneous ovarian hyperstimulation syndrome secondary to hypothyroidism may be the cause of ovarian enlargement, and levothyroxine replacement seems an appropriate primary therapeutic option. Proper endocrinological assessment of patients is recommended as it may avoid unfavorable outcomes.

Gut microbiota: A potential therapeutic target for management of diabetic retinopathy?

Diabetic Retinopathy (DR) is one of the main complications of Diabetes Mellitus (DM), drastically impacting individuals of working age over the years, being one of the main causes of blindness in the world. The existing therapies for its treatment consist of measures that aim only to alleviate the existing clinical signs, associated with the microvasculature. These treatments are limited only to the advanced stages and not to the preclinical ones. In response to a treatment with little resolution and limited for many patients with DM, investigations of alternative therapies that make possible the improvement of the glycemic parameters and the quality of life of subjects with DR, become extremely necessary. Recent evidence has shown that deregulation of the microbiota (dysbiosis) can lead to low-grade, local and systemic inflammation, directly impacting the development of DM and its microvascular complications, including DR, in an axis called the intestine-retina. In this regard, the present review seeks to comprehensively describe the biochemical pathways involved in DR as well as the association of the modulation of these mechanisms by the intestinal microbiota, since direct changes in the microbiota can have a drastic impact on various physiological processes. Finally, emphasize the strong potential for modulation of the gut-retina axis, as therapeutic and prophylactic target for the treatment of DR.

Management of Traumatic Brain Injury at a Medium Complexity Hospital in a Remote Area of Amazonas, 2017-2019.

OBJECTIVE: To describe the traumatic brain injury (TBI) care in the city of Coari, Amazonas, from 2017-2019. METHODS: Ecological study based on the analysis of the data obtained by the Epidemiology Service of the Regional Hospital of Coari regarding TBI attendances in the emergency room from January 2017 to October 2019. According to the Glasgow Coma Scale, TBI was classified as mild, moderate, or severe. Other variables analyzed were sex, age, main causes of TBI, hospitalizations at the admission unit, and transfers to another health center and means of transport used. RESULTS: One hundred ten admissions were registered: 24 mild TBI, 51 moderate, and 35 severe; higher prevalence among men (70%); and age between 20 and 29 years (29%). The main causes were motorcycle accidents (42.7%), falls (29%), and physical aggression (21%). Some 69% of the patients admitted required to be transferred to another health center, with aerial intensive care unit (ICU) as the most significant means of transport (48.7%). Thirty patients hospitalized at the admission unit progressed with hospital discharge and 4 died. CONCLUSIONS: The profile of patients affected by TBI in the city of Coari was characterized by male victims of motorcycle accidents with age between 20 and 29 years. The high transfer rates indicates the need for a better neurotrauma assistance. Further investigations and studies associated with regional specificities are essential to recommend changes on the scope of public health and therefore decrease the incidence of TBI.