Nivolumab for newly and recurrent glioblastoma multiforme treatment: A systematic review and meta-analysis.

OBJECTIVE: We conducted a systematic review and meta-analysis aiming to assess the efficacy and safety of Nivolumab treatment in patients with newly diagnosed and recurrent glioblastoma multiforme (GBM). DATA SOURCES: Our study followed the guidelines outlined in the preferred reporting items for systematic reviews and meta-analyses (PRISMA) recommendations. The protocol for this review can be found in the International Prospective Register of Systematic Reviews Database (CRD42022340071). We performed searches on the Medline, PubMed, Embase, Scopus, and Web of Science databases. DATA SUMMARY: A total of 545 studies were identified through our comprehensive search across the five databases (PubMed: 78, Embase: 82, Medline: 173, Scopus: 138, Web of Science: 74). After conducting a thorough analysis, our meta-analysis indicated that treatment with Nivolumab led to improved overall survival (OS) outcomes in newly diagnosed glioblastoma patients, as evidenced by a prolonged median OS based on trial data. However, there was no significant beneficial effect observed in terms of median progression-free survival (PFS), as well as OS at 6, 12, and 24 months. Furthermore, our results demonstrated no efficacy of Nivolumab in the treatment of recurrent GBM patients. CONCLUSIONS: In conclusion, Nivolumab demonstrated promising results that warrant further investigation for its use in newly diagnosed glioblastoma patients. However, its effectiveness was not observed in the context of recurrent GBM.

In Situ Maturated Early-Stage Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes Improve Cardiac Function by Enhancing Segmental Contraction in Infarcted Rats.

The scant ability of cardiomyocytes to proliferate makes heart regeneration one of the biggest challenges of science. Current therapies do not contemplate heart re-muscularization. In this scenario, stem cell-based approaches have been proposed to overcome this lack of regeneration. We hypothesize that early-stage hiPSC-derived cardiomyocytes (hiPSC-CMs) could enhance the cardiac function of rats after myocardial infarction (MI). Animals were subjected to the permanent occlusion of the left ventricle (LV) anterior descending coronary artery (LAD). Seven days after MI, early-stage hiPSC-CMs were injected intramyocardially. Rats were subjected to echocardiography pre-and post-treatment. Thirty days after the injections were administered, treated rats displayed 6.2% human cardiac grafts, which were characterized molecularly. Left ventricle ejection fraction (LVEF) was improved by 7.8% in cell-injected rats, while placebo controls showed an 18.2% deterioration. Additionally, cell-treated rats displayed a 92% and 56% increase in radial and circumferential strains, respectively. Human cardiac grafts maturate in situ, preserving proliferation with 10% Ki67 and 3% PHH3 positive nuclei. Grafts were perfused by host vasculature with no evidence for immune rejection nor ectopic tissue formations. Our findings support the use of early-stage hiPSC-CMs as an alternative therapy to treat MI. The next steps of preclinical development include efficacy studies in large animals on the path to clinical-grade regenerative therapy targeting human patients.

Long-term single-cell passaging of human iPSC fully supports pluripotency and high-efficient trilineage differentiation capacity.

OBJECTIVES: To establish a straightforward single-cell passaging cultivation method that enables high-quality maintenance of human induced pluripotent stem cells without the appearance of karyotypic abnormalities or loss of pluripotency. METHODS: Cells were kept in culture for over 50 passages, following a structured chronogram of passage and monitoring cell growth by population doubling time calculation and cell confluence. Standard procedures for human induced pluripotent stem cells monitoring as embryonic body formation, karyotyping and pluripotency markers expression were evaluated in order to assess the cellular state in long-term culture. Cells that underwent these tests were then subjected to differentiation into keratinocytes, cardiomyocytes and definitive endoderm to evaluate its differentiation capacity. RESULTS: Human induced pluripotent stem cells clones maintained its pluripotent capability as well as chromosomal integrity and were able to generate derivatives from the three germ layers at high passages by embryoid body formation and high-efficient direct differentiation into keratinocytes, cardiomyocytes and definitive endoderm. CONCLUSIONS: Our findings support the routine of human induced pluripotent stem cells single-cell passaging as a reliable procedure even after long-term cultivation, providing healthy human induced pluripotent stem cells to be used in drug discovery, toxicity, and disease modeling as well as for therapeutic approaches.

Implications of body condition and seasonality on morphological and functional parameters of testes of Myotis nigricans (Chiroptera: Vespertilionidae).

The insectivorous bat Myotis nigricans is widely distributed throughout the Neotropics, including Brazil, and has a reproductive biology that is affected by climate and food availability. To evaluate the reproductive capacity of this species, morphofunctional parameters of the testes were correlated with environmental variables and the body condition of individuals captured. After bats had been killed, their testes were removed, fixed in Karnovsky's fluid for 24h and embedded in resin for evaluation by light microscopy. The mean annual tubulosomatic index (0.58%) and the percentage of seminiferous tubules in the testes (88.96%) were the highest ever recorded for the Order Chiroptera. The percentage of Leydig cells and volume of the cytoplasm of Leydig cells were higher in the rainy than dry season (80.62±3.19% and 573.57±166.95µm, respectively; mean±s.d.). Conversely, the percentage of nuclei of the Leydig cells in the dry season (26.17±3.70%; mean±s.d.) and the total number of Leydig cells (6.38±1.84×109; mean±s.d.) were higher in the dry season. The results of the present study could help in future conservation of these bats because they provide a better understanding of the bats' reproductive strategies and how the species can adapt to changes.

Quantification of argyrophillic, argentaffin and insulin immunoreactive cells in the small intestine in the opossum Didelphis aurita (Wied-Neuwied, 1826) / Quantificação das células argirófilas, argentafins e imunorreativas à insulina nos diferentes segmentos do intestino delgado do gambá Didelphis aurita (Wied-Neuwied, 1826)

The objective of this study was to quantify argyrophillic, argentaffin and insulin immunoreactive endocrine cells in the different segments of the small intestine of Didelphis aurita and measure probable differences in the number of these cells between adult and post-pubertal animals. Biological material consisted of ten male and female opossums specimen, divided in two groups according to weigh. The utilized staining techniques were Grimelius, modified Masson-Fontana and direct immunoperoxidase. Results indicated a predominance of argyrophillic cells in the small intestine of opossums from class 1 and 2, with an average of 52.58 and 56.15 cells mm-2, respectively; of which, the average number of total endocrine cells, argyrophillic and argentaffin cells decreased distally in the intestinal segments of opossums from classes 1 and 2. No significant difference was observed for the insulin immunoreactive cells between the intestinal segments of animals from class 2. A greater number of insulin immunoreactive cells was encountered in the jejunum and ileum of animals from class 2 when compared to the same segment in animals from class 1.

Os objetivos deste trabalho foram quantificar as células endócrinas argirófilas, argentafins e imunorreativas à insulina nos diferentes segmentos do intestino delgado de gambás Didelphis aurita e mensurar prováveis diferenças no número destas células entre animais adultos e pós-púberes. Dez exemplares de gambás D. aurita machos e fêmeas foram divididos em dois grupos de acordo com o peso. As técnicas de coloração utilizadas foram Grimelius, Masson-Fontana modificado e Imunoperoxidase direta. Os resultados indicaram um predomínio das células argirófilas no intestino delgado de gambás da classe 1 e 2, com uma média de 52,58 e 56,15 células mm-2, respectivamente. O número médio de células endócrinas totais, células argirófilas e argentafins decresceu distalmente nos segmentos intestinais dos gambás das classes 1 e 2. Nenhuma diferença significativa foi observada para as células imunorreativas à insulina entre os segmentos intestinais dos animais da classe 2. Foi encontrado maior número de células imunorreativas à insulina no jejuno e íleo de animais da classe 2 quando comparado ao mesmo segmento em animais da classe 1.

Quantification of argyrophillic, argentaffin and insulin immunoreactive cells in the small intestine in the opossum Didelphis aurita (Wied-Neuwied, 1826) - doi: 10.4025/actascibiolsci.v33i4.8644 / Quantification of argyrophillic, argentaffin and insulin immunoreactive cells in the small intestine in the opossum Didelphis aurita (Wied-Neuwied, 1826) - doi: 10.4025/actascibiolsci.v33i4.8644

The objective of this study was to quantify argyrophillic, argentaffin and insulin immunoreactive endocrine cells in the different segments of the small intestine of Didelphis aurita and measure probable differences in the number of these cells between adult and post-pubertal animals. Biological material consisted of ten male and female opossums specimen, divided in two groups according to weigh. The utilized staining techniques were Grimelius, modified Masson-Fontana and direct immunoperoxidase. Results indicated a predominance of argyrophillic cells in the small intestine of opossums from class 1 and 2, with an average of 52.58 and 56.15 cells mm-2, respectively; of which, the average number of total endocrine cells, argyrophillic and argentaffin cells decreased distally in the intestinal segments of opossums from classes 1 and 2. No significant difference was observed for the insulin immunoreactive cells between the intestinal segments of animals from class 2. A greater number of insulin immunoreactive cells was encountered in the jejunum and ileum of animals from class 2 when compared to the same segment in animals from class 1.

The objective of this study was to quantify argyrophillic, argentaffin and insulin immunoreactive endocrine cells in the different segments of the small intestine of Didelphis aurita and measure probable differences in the number of these cells between adult and post-pubertal animals. Biological material consisted of ten male and female opossums specimen, divided in two groups according to weigh. The utilized staining techniques were Grimelius, modified Masson-Fontana and direct immunoperoxidase. Results indicated a predominance of argyrophillic cells in the small intestine of opossums from class 1 and 2, with an average of 52.58 and 56.15 cells mm-2, respectively; of which, the average number of total endocrine cells, argyrophillic and argentaffin cells decreased distally in the intestinal segments of opossums from classes 1 and 2. No significant difference was observed for the insulin immunoreactive cells between the intestinal segments of animals from class 2. A greater number of insulin immunoreactive cells was encountered in the jejunum and ileum of animals from class 2 when compared to the same segment in animals from class 1.

Oviductal structure and ultrastructure of the oviparous gecko, Hemidactylus mabouia (Moreau De Jonnès, 1818).

Lizards of the family Gekkonidae display a variety of reproductive patterns, as evidenced by the presence of viviparous and oviparous species. The species Hemidactylus mabouia is oviparous. We examined, in vitellogenic females, oviductal structure by light microscopy after routine histological and histochemical techniques, as well as by scanning and transmission electron microscopy. The oviduct is composed of four different regions: the infundibulum, which opens into the coelomic cavity and receives the oocyte released at the time of ovulation; the uterine tube, where sperm storage takes place; the uterus, which is responsible for the eggshell production; and the vagina, the final portion of the oviduct that leads to the cloaca. The oviductal structure of H. mabouia is similar to that of other oviparous lizard species and can be useful for morphological comparative analysis among reptile species.

Anatomia do tubo digestório de leporinus macrocephalus Garavello & Britski, 1988 (Characiformes, Anostomidae) em relação ao seu habita alimentar / Anatomy of the digestive tract of leporinus macrocephalus Garavello & Britski, 1988 (Characiformes, Anostomidae) in relation to its alimentary habit

Visando relacionar características anatômicas do tubo digestório de Leporinus macrocephalus com seu hábito alimentar onívoro, foram analisados 20 exemplares desta espécie, com 22 a 28cm de comprimento-padrão. A anatomia do tubo digestório de L. macrocephalus é, em geral, semelhante a dos demais Anostomidae. O esôfago é curto e cilíndrico; o estômago é do tipo cecal em “Y”; o intestino médio apresenta arranjo em “N”; e o intestino posterior é retilíneo e longo, sem valva e esfíncter íleorretais. O padrão de pregas da mucosa dos órgãos digestórios favorece as suas respectivas funções: no esôfago permite a distensibilidade e facilitando a passagem do alimento; no estômago, permite a distensibilidade da parede para recepção e armazenamento do alimento nas regiões cárdica e cecal, além do esvaziamento gástrico pela região pilórica; nas alças intestinais resulta em aumento da superfície, maior distensibilidade da parede intestinal, retardo no tempo de passagem do bolo alimentar e, conseqüentemente, maior exposição às enzimas digestivas e maior taxa de absorção dos nutrientes; e no intestino posterior, anteriormente ao ânus, permite a condução do bolo fecal e a sua expulsão do tubo digestório.

Aiming to relate the anatomical characteristics of the alimentary tract of Leporinus macrocephalus with its omnivorous alimentary habit, 20 specimens were analyzed, with 12 to 28cm of Standard-length. The anatomy of the alimentary tract of L. macrocephalus is similar to the of other Anostomidae. The esophagus is short and cylindrical; the stomach is like cecal shape in "Y"; the medium intestine presents arrangement in "N"; and the posterior intestine is rectilinial and long, without ileorectals valve. The pattern of folds of the mucous membrane of the digestive organs favors the its respective functions: in the esophagus allows distention and facilitates the passage of the food; in the stomach allows the distensibility of the wall for reception and storage of the food in the cardic and caecal areas, besides the gastric emptying in the piloric area; in the intestinal loops results in increase of the surface, larger distensibility of the intestinal wall, delay in the time of passage of the digesta and, consequently, larger exhibition to the digestive enzymes and larger rate of absorption of the nutrients; and in the posterior intestine, previously to the anus, allows the conduction of the feces and its expulsion of the alimentary tract.