Impact of Formate Supplementation on Body Weight and Plasma Amino Acids.

Current nutritional recommendations are focused on energy, fat, carbohydrate, protein and vitamins. Less attention has been paid to the nutritional demand of one-carbon units for nucleotide and methionine synthesis. Here, we investigated the impact of sodium formate supplementation as a nutritional intervention to increase the dietary intake of one-carbon units. A cohort of six female and six male mice received 125 mM of sodium formate in the drinking water for three months. A control group of another six female and six male mice was also followed up for the same period of time. Tail vein blood samples were collected once a month and profiled with a haematology analyser. At the end of the study, blood and tissues were collected for metabolomics analysis and immune cell profiling. Formate supplementation had no significant physiological effect on male mice, except for a small decrease in body weight. Formate supplementation had no significant effect on the immune cell counts during the intervention or at the end of the study in either gender. In female mice, however, the body weight and spleen wet weight were significantly increased by formate supplementation, while the blood plasma levels of amino acids were decreased. Formate supplementation also increased the frequency of bifidobacteria, a probiotic bacterium, in the stools of female mice. We conclude that formate supplementation induces physiological changes in a gender-specific manner.

Mammals divert endogenous genotoxic formaldehyde into one-carbon metabolism.

The folate-driven one-carbon (1C) cycle is a fundamental metabolic hub in cells that enables the synthesis of nucleotides and amino acids and epigenetic modifications. This cycle might also release formaldehyde, a potent protein and DNA crosslinking agent that organisms produce in substantial quantities. Here we show that supplementation with tetrahydrofolate, the essential cofactor of this cycle, and other oxidation-prone folate derivatives kills human, mouse and chicken cells that cannot detoxify formaldehyde or that lack DNA crosslink repair. Notably, formaldehyde is generated from oxidative decomposition of the folate backbone. Furthermore, we find that formaldehyde detoxification in human cells generates formate, and thereby promotes nucleotide synthesis. This supply of 1C units is sufficient to sustain the growth of cells that are unable to use serine, which is the predominant source of 1C units. These findings identify an unexpected source of formaldehyde and, more generally, indicate that the detoxification of this ubiquitous endogenous genotoxin creates a benign 1C unit that can sustain essential metabolism.

Carcinoma de células escamosas de la piel infiltrando hueso: presentación de un caso / Squamous cell carcinoma of the skin infiltrating bone. Case report

Introducción: el carcinoma de células escamosas o epidermoide como también se le denomina, es el segundo tumor no melanoma más frecuente de la piel de las zonas expuestas a los rayos solares y es más común en las personas mayores. Tiene mayor incidencia en los hombres, aunque pueden ser vistos en ambos sexos. Presentación de caso: paciente de sexo femenino, 57 años de edad, raza indígena, con antecedentes de habérsele removido hace aproximadamente 30 años una lesión en la pierna derecha, en un Sanatorio Privado no precisando el resultado anatomopatológico de la misma. Acude a emergencias del Hospital Nacional Regional de Escuintla, (HNRE), Guatemala, porque desde hace aproximadamente 4 meses comenzó con una lesión, ulcerada, pequeña en la misma pierna y según refiere la paciente en el mismo lugar, que se trató inicialmente con remedios caseros, sin precisar cuáles, pero que no mejoró, al contrario comenzó a crecer de forma exofítica y a infectarse secundariamente. Se decide ingresar en el Servicio de Cirugía de Mujeres para estudio y posterior tratamiento. Se realiza biopsia de piel para un diagnóstico certero, el diagnóstico anatomopatológico confirma la existencia de un carcinoma de células escamosas bien diferenciado e infiltrante de piel, se toma la conducta de consultar y remitir el caso para el Hospital Roosevelt de Ciudad de Guatemala para ser interconsultado con un especialista cirujano oncólogo. Discusión: el carcinoma epidermoide o también conocido como carcinoma espinocelular, es el segundo cáncer de piel no melanoma más frecuente, siendo precedido por el carcinoma de células basales, el mismo se deriva de alteraciones a nivel de la epidermis específicamente de los queratinocitos.Conclusión: el carcinoma de células escamosas (epidermoide) surge por alteraciones de queratinocitos de la epidermis y es capaz de infiltrar estructuras óseas(AU)

Introduction: the squamous or epidermoid cell carcinoma is thesecond most common non-melanoma tumor in the skin areas exposed to sunlight, and it is more common in older people. Its incidence is higher in men, but it can be seen in both sexes. Case presentation: a 57-year-old female patient, native, with a clinical antecedent of a removed lesion in her right leg about 30 years ago in a private hospital, without specifying its anatomopathological result. She went to the Emergency Service at the National Regional Hospital in Escuintla, Guatemala, because four months ago she began with a small ulcerated injure in the same leg, and as she reported, in the same place, which was initially treated with home remedies, without specifying which ones, but the injure did not get better, otherwise it began to grow in an exophytic way and became secondarily infected. It was decided then to hospitalize the patient in the Surgery Service of Women for the study and later treatment. It was performed a skin biopsy to obtain an accurate diagnosis, the anatomopathological diagnosis confirmed the existence of a squamous cell carcinoma, well differentiated and infiltrating of the skin. It was decided then to consult and send the case to Roosevelt Hospital in Guatemala to be consulted with a surgeon specialist in oncology. Discussion: the epidermoid carcinoma, also known as spinocellular carcinoma is the second most common non-melanoma skin cancer, preceded by basal cell carcinoma; it is derived from alterations in the epidermis, specifically of keratinocytes. Conclusion:the squamous (epidermoid) cell carcinoma arises from alterations in epidermal keratinocytes and it can infiltrate bone structures(EU)