Search

Ubiquitination is a prevalent post-translational modification that plays a crucial role in a wide range of pathophysiological processes, including cell proliferation, apoptosis, autophagy, immune response, and DNA damage repair. Among the enzymes involved in ubiquitination, E3 ubiquitin ligases are particularly significant, serving as key regulators of numerous diseases, including tumours. This review focuses on HECW2 (HECT, C2, and WW domain-containing E3 ubiquitin protein ligase 2, also known as NEDL2), providing a comprehensive overview of its interactors and its pathological roles in tumorous cancer and other diseases. The insights gained from this review may contribute to the development of novel treatment strategies for various diseases, particularly tumours. [ABSTRACT FROM AUTHOR]

One of the most typical dishes of traditional Mexican cuisine is pozole, made with nixtamalized maize. This dish has a special place as part of the identity of Mexican culture. However, it is time-consuming to prepare. With an increasing demand for precooked maize for pozole and the limited information on its preparation process, this study aims to assess the impact of both traditional (TN) and commercial nixtamalization (CN) on the quality of processed maize and its reception by consumers, focusing on the three most popular maize landraces used in pozole recipes. This study was carried out with the Cacahuacintle ('CAC'), Elotes Occidentales ('EO') and Ancho ('AN') landraces, which were nixtamalized using the traditional method (only lime) and the commercial method (lime + additives) and the grain was flowered. The quality of the flowered grain was determined, and a sensory analysis consisting of magnitude of difference tests, a descriptive analysis, affective test and evaluation of consumer preferences was carried out. The 'CAC' landrace, when processed traditionally, yielded the highest sensory and commercial quality. The 'EO' landrace demanded a longer flowering time, resulting in less volume but retaining the aleurone layer. This characteristic helped preserved a portion of the anthocyanins. Consistently, maize landraces subjected to traditional nixtamalization displayed higher ratings for attributes related to masa and nejayote aroma. The 'CAC' landrace subjected to CN faced challenges in acceptability due to odors of acetic acid and sulfuric acid. These findings underscore the importance and advantages the TN techniques. They also emphasize the need to preserve grain quality and meeting consumer preferences when exploring alternative maize processing methods for emerging markets. [ABSTRACT FROM AUTHOR]

Background: NR2F1 mutations are associated with Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Although ~ 46.7% of BBSOAS patients present with epilepsy, which is always drug-resistant and associated with higher rates of behavioral and cognitive problems, the treatment and outcomes of NR2F1-related epilepsy have rarely been described. Here, we present new cases of BBSOAS-related epilepsy and summarize all previously reported cases to explore the effective treatment for this type of epilepsy. Methods: We identified six new Chinese cases of BBSOAS with epilepsy. Five different de novo heterozygous NR2F1 mutations were identified in these cases, including two novel mutations c.365G > T, p.Cys122Phe and c.449G > T, p.Gly150Val. By combining the six cases and 14 previously reported cases, we analyzed the characteristics and treatment outcomes of NR2F1-related epilepsy. Results: Twelve of the 20 patients (60%) had infantile epileptic spasms, while the other patients had generalized tonic/tonic-clonic, focal, myoclonic, absence, or unclassified seizures. Several anti-seizure medications, steroids, and a ketogenic diet were administered in these cases. However, seizures were controlled in only 50% of previously reported cases, while all of the six new cases became seizure-free after perampanel as an add-on treatment. The average time from the addition of perampanel to seizure control was 7.33 ± 4.59 months (range, 1–12 months). The median time to seizure freedom was 14 months (1–32 months, > 19 months in 3 cases). The average dosage of perampanel needed for epilepsy control was 0.22 ± 0.17 mg/kg per day. Conclusions: In this paper, we comprehensively summarized the clinical characteristics, treatments and outcomes of NR2F1-related epilepsy for the first time. Perampanel exhibits dramatic efficacy for NR2F1-related epilepsy. This will help optimize the treatment of this type of epilepsy and provide clues for its pathogenic mechanisms. The two novel mutations expand the genotype spectrum of this disease. [ABSTRACT FROM AUTHOR]

Background: Smith-Kingsmore syndrome (SKS) is a rare autosomal dominant disorder caused by de novo mutations of gene MTOR in most cases and germline mosaicism in a few cases. The first case of SKS was reported in 2013. The incidence of SKS remains unknown. The clinical manifestations of SKS are diverse, and common features are macrocephaly, intellectual disability, and seizures. Some patients with SKS have special facial features. Case presentation: The case was a 5-month-old baby girl, who was admitted to the hospital for nystagmus, delayed development for 2 months, and intermittent convulsions for 2 days. The patient had a head circumference of 42 cm (+ 2SD), and showed facial deformity, low limb muscle tension, large areas of pigmentation, as well as mosaic patchy and strip-like pigment loss in her trunk and limbs. Meanwhile, her development was lagging behind peers. Physical examination did not reveal other abnormalities. She was diagnosed with SKS based on whole-exome sequencing combined with clinical symptoms and signs. She successively received treatment with adrenocorticotropic hormone, methylprednisolone sodium succinate, topiramate, levetiracetam, and zonisamide to reduce the number of convulsions in a short time, but drug resistance appeared thereafter. After combined treatment with multiple antiseizure medications, the patient still had seizures, but the amplitude of limb movement during the seizures was reduced compared to that before treatment. Conclusions: This case expanded the phenotypic spectrum of SKS for diagnosis. We also review the related literature to promote the awareness, diagnosis, clinical management, and follow-up of SKS patients with MTOR mutations. [ABSTRACT FROM AUTHOR]

Nixtamalization, which means cooking maize in alkaline water, is the central technique for the culinary use of maize in Mexico and Central America. Without this procedure, relying on maize as the basic starch staple is inadequate because of nutriment deficiencies. Mexico has more than 50 principal racial types of maize, and these differ in grain qualities that can require the adjustment of the nixtamalization process. Properties such as hardness and grain composition influence nixtamalization because they are related to the absorption of water that occurs during cooking and steeping. Some maize preparations, like tortillas and tostadas, can also require the adjustment of nixtamalization to obtain a high-quality foodstuff. We studied how women in three regions of the state of Chiapas, which differ in the prevalent maize race available, prepare their nixtamal and whether they make changes according to the type of food they prepare. Interviews of 30 women follow the measure of relevant variables when the women prepared nixtamal. We found that nixtamalization is adjusted for different grain hardnesses and for environmental conditions. Variations were found in the cooking time of the nixtamal, in the amount of time the nixtamal was steeped, and in a special process of double boiling of the nixtamal performed by some women for tostadas. Women that specialize in production for the market have developed variations preferred by consumers. As practiced by women in Chiapas, nixtamalization is a flexible technique that is adjusted for maize type and for food preparations. [ABSTRACT FROM AUTHOR]

Cisplatin is a widely used chemotherapeutic agent for treatment of various cancers. However, treatment with cisplatin is associated with drug resistance and several adverse side effects such as nephrotoxicity, reduced immunity towards infections and hearing loss. A Combination of cisplatin with other drugs is an approach to overcome drug resistance and reduce toxicity. The combination therapy also results in increased sensitivity of cisplatin towards cancer cells. The mitogen activated protein kinase (MAPK) pathway in the cell, consisting of extracellular signal regulated kinase, c-Jun N-terminal kinase, p38 kinases, and downstream mediator p90 ribosomal s6 kinase (RSK); is responsible for the regulation of various cellular events including cell survival, cell proliferation, cell cycle progression, cell migration and protein translation. This review article demonstrates the role of MAPK pathway in cisplatin based therapy, illustrates different combination therapy involving cisplatin and also shows the importance of targeting MAPK family, particularly RSK, to achieve increased anticancer effect and overcome drug resistance when combined with cisplatin. [ABSTRACT FROM AUTHOR]