Ampelopsis japonica aqueous extract improves ovulatory dysfunction in PCOS by modulating lipid metabolism.

Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine and metabolic disorder that is closely associated with the proliferation and apoptosis of ovarian granulosa cells (GCs). Ampelopsis japonica (AJ) is the dried tuberous root of Ampelopsis japonica (Thunb.) Makino (A. japonica), with anti-inflammatory, antioxidant, antibacterial, antiviral, wound-healing, and antitumor properties; however, it is unclear whether this herb has a therapeutic effect on PCOS. Therefore, this study aimed to investigate the pharmacological effect of AJ on PCOS and reveal its potential mechanism of action. A PCOS rat model was established using letrozole. After establishing the PCOS model, the rats received oral treatment of AJ and Diane-35 (Positive drug: ethinylestradiol + cyproterone tablets) for 2 weeks. Lipidomics was conducted using liquid-phase mass spectrometry and chromatography. AJ significantly regulated serum hormone levels and attenuated pathological variants in the ovaries of rats with PCOS. Furthermore, AJ significantly reduced the apoptotic rate of ovarian GCs. Lipidomic analysis revealed that AJ modulated glycerolipid and glycerophospholipid metabolic pathways mediated by lipoprotein lipase (Lpl), diacylglycerol choline phosphotransferase (Chpt1), and choline/ethanolamine phosphotransferase (Cept1). Therefore, we established that AJ may reduce ovarian GC apoptosis by modulating lipid metabolism, ultimately improving ovulatory dysfunction in PCOS. Therefore, AJ is a novel candidate for PCOS treatment.

Anti-tumor pharmacology of natural products targeting mitosis.

Cancer has been an insurmountable problem in the history of medical science. The uncontrollable proliferation of cancer cells is one of cancer's main characteristics, which is closely associated with abnormal mitosis. Targeting mitosis is an effective method for cancer treatment. This review summarizes several natural products with anti-tumor effects related to mitosis, focusing on targeting microtubulin, inducing DNA damage, and modulating mitosis-associated kinases. Furthermore, the main disadvantages of several typical compounds, including drug resistance, toxicity to non-tumor tissues, and poor aqueous solubility and pharmacokinetic properties, are also discussed, together with strategies to address them. Improved understanding of cancer cell mitosis and natural products may pave the way to drug development for the treatment of cancer.

A Perspective on Extreme Open Science: Companies Sharing Compounds without Restriction.

Although the human genome provides the blueprint for life, most of the proteins it encodes remain poorly studied. This perspective describes how one group of scientists, in seeking new targets for drug discovery, used open science through unrestricted sharing of small molecules to shed light on dark matter of the genome. Starting initially with a single pharmaceutical company before expanding to multiple companies, a precedent was established for sharing published kinase inhibitors as chemical tools. The integration of open science and kinase chemogenomics has supported the study of many new potential drug targets by the scientific community.

Ruxolitinibe para o tratamento de mielofibrose / Ruxolitinib for the treatment of myelofibrosis

CONTEXTO: A mielofibrose mieloproliferativa pode apresentar-se como um transtorno novo (mielofibrose primária - MFP) ou evoluir secundariamente a partir de policitemia vera anterior ou trombocitemia essencial (MF Pos-PV ou MF Pos-TE respectivamente). O termo neoplasia mieloproliferativa (NMP) associada a mielofibrose tem sido sugerido para abranger todas estas entidades. Independentemente de a mielofibrose ser primária ou secundária, a doença é caracterizada por uma proliferação clonal de células estaminais hematopoiéticas associada a um padrão estromal característico, a um esfregaço de sangue leuco eritroblástico e a níveis elevados de várias citocinas inflamatórias e pró-angiogênicas. TECNOLOGIA: Ruxolitinibe. PERGUNTA: Ruxolitinibe é eficaz e seguro para o tratamento de mielofibrose? EVIDÊNCIAS: Ruxolitinibe foi melhor do que o placebo para o desfecho sobrevida global, redução do tamanho do baço e qualidade de vida. Não houve diferenças estatisticamente significativas entre ruxolitinibe e melhor terapia disponível (BAT) para sobrevida global e sobrevida livre de progressão. Ruxolitinibe foi melhor do que BAT para os desfechos qualidade de vida e redução do baço. O risco de eventos adversos não hematológicos de grau 3 ou 4 (incluindo fadiga, artralgia, náusea, diarreia, dor nas extremidades e pirexia) foi semelhante entre ruxolitinibe e placebo ou BAT. A confiança nas estimativas dos resultados dos ensaios clínicos incluídos na revisão sistemática foi baixa devido ao viés de desenho e às suas amostras limitadas que resultaram em resultados imprecisos. Além disso, os dados devem ser interpretados com cautela, pois são baseados em estudos patrocinados pela indústria. CONCLUSÕES: A evidência foi considerada insuficiente para conclusões consistentes sobre a eficácia e segurança do ruxolitinibe no tratamento da mielofibrose. São necessários mais estudos que comparem o ruxolitinibe com as opções terapêuticas disponíveis.

Molecular pathways: targeting the kinase effectors of RHO-family GTPases.

RHO GTPases, members of the RAS superfamily of small GTPases, are adhesion and growth factor-activated molecular switches that play important roles in tumor development and progression. When activated, RHO-family GTPases such as RAC1, CDC42, and RHOA, transmit signals by recruiting a variety of effector proteins, including the protein kinases PAK, ACK, MLK, MRCK, and ROCK. Genetically induced loss of RHO function impedes transformation by a number of oncogenic stimuli, leading to an interest in developing small-molecule inhibitors that either target RHO GTPases directly, or that target their downstream protein kinase effectors. Although inhibitors of RHO GTPases and their downstream signaling kinases have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to facilitate pharmaceutical research and development and is a promising therapeutic strategy.

Tofacitinib y otros inhibidores de las cinasas en el tratamiento de la psoriasis / Tofacitinib and Other Kinase Inhibitors in the Treatment of Psoriasis

Las proteínas cinasas desempeñan un papel fundamental en las vías de señalización intracelular implicadas tanto en la proliferación celular como en la inflamación. El mejor conocimiento de estas vías metabólicas, y del mecanismo patogénico de las señales intracelulares de la psoriasis, está provocando el desarrollo e investigación de un nuevo grupo de fármacos en el tratamiento de esta enfermedad y de otros procesos inflamatorios. Los inhibidores de las cinasas son moléculas de pequeño tamaño que van a permitir un tratamiento vía oral o tópico. El futuro papel de estos fármacos dentro del arsenal terapéutico de la psoriasis está todavía por determinar, ya que la mayoría de moléculas están en fases precoces de investigación. Su hipotético coste inferior al de los tratamientos biológicos pudiera favorecer su aprobación en los próximos años. Tofacitinib, un inhibidor de las cinasas Janus, es el fármaco con investigación más avanzada y resultados prometedores (AU)

Protein kinases play a crucial role in the intracellular signaling pathways involved in inflammation and cell proliferation. Advances in our understanding of these metabolic pathways and of the role played by intracellular signaling in the pathogenesis of psoriasis have led to research in this area and the development of a new class of drugs for the treatment of psoriasis and other inflammatory processes. Since kinase inhibitors are small molecules, oral and topical treatments are possible. The future role of these molecules in the therapeutic arsenal used to treat psoriasis is as yet unknown because in most cases they are still in the early stages of research. The fact that these drugs may cost much less than biologic therapies could favor their approval in coming years. Tofacitinib, a Janus kinase inhibitor, is the drug that has reached the most advanced stage of research and has shown the most promising results (AU)

[Morphology of thrombolysis as affected by a plasmakinase preparation]. / Morfologiia lizisa tromba pod deistviem preparata plazmakinazy.

The effect of a new thrombolytic preparation, plasmakinase, on experimental coagulates and thrombi was studied morphologically. Histological and electron microscopic studies revealed changes in the structure of fibrin fibers in the form of separation of fibers into individual protofibrils and subsequent degradation into globular particles. There were disorders in the fibrin association with blood cells, washing out of partially hemolyzed red blood cells into the bloodstream, decrease in the size of thrombi and restoration of the vessel lumen.