Potential molecular patterns for tuberculosis susceptibility in diabetic patients with poor glycaemic control: a pilot study.

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.

Influence of coffee roasting degree on inflammatory and oxidative stress markers in high-fructose and saturated fat-fed rats.

The objective of this study was to evaluate the effect of roasting coffee degree on inflammatory (NF-kß F-6 and TNF-α) and stress oxidative markers (malondialdehyde (MDA), nitric oxide (NO) end product concentrations, catalase (CAT), and superoxide dismutase (SOD) in high-fructose and saturated fat (HFSFD)-fed rats. Roasting was performed using hot air circulation (200 °C) for 45 and 60 min, obtaining dark and very dark coffee, respectively. Male Wistar rats were randomly assigned to receive a) unroasted coffee, b) dark coffee, c) very dark coffee, or distilled water for the control group (n = 8). Coffee brews (7.4 mL/per day equivalent to 75 mL/day in humans) were given by gavage for sixteen weeks. All treated groups significantly decreased NF-kß F-6 (∼30 % for unroasted, ∼50 % for dark, and âˆ¼ 75 % for very dark group) and TNF-α in the liver compared with the control group. Additionally, TNF-α showed a significant reduction in all treatment groups (∼26 % for unroasted and dark groups, and âˆ¼ 39 % for very dark group) in adipose tissue (AT) compared with the negative control. Regarding oxidative stress makers, all coffee brews exerted antioxidant effects in serum, AT, liver, kidney, and heart. Our results revealed that the anti-inflammatory and antioxidant effects of coffee vary according to the roasting degree in HFSFD-fed rats.

Hypomagnesemia and 25-hydroxyvitamin D deficiency in patients with long COVID.

Clinical manifestations related to hypomagnesemia and/or deficiency of vitamin D are frequent in patients with an extended course of coronavirus disease-2019 (long COVID). To evaluate hypomagnesemia and hydroxyvitamin D deficiency in patients with long COVID. A total of 125 adults with a diagnosis of long COVID were enrolled in a cross-sectional study. Participants were allocated into a risk (hypomagnesemia and hydroxyvitamin D deficiency) or control (serum magnesium and hydroxyvitamin D within normal ranges) group. Hypomagnesemia and 25-hydroxyvitamin D deficiency were defined based on serum level ≤1.8 mg/dL and <30 ng/mL, respectively. The number of clinical manifestations of long COVID were significantly higher in the risk compared to the control group. Fatigue, memory loss, attention disorders, joint pain, anxiety, sleep disorders, myalgia, and depression, all of which are related to hypomagnesemia and/or 25-hydroxyvitamin D deficiency, were among the 10 most frequent manifestations in the risk group. The adjusted odds ratio for the association between hypomagnesemia and hydroxyvitamin D deficiency during long COVID was 3.1; 95% CI 2.3-12.4, p=0.005. Our results show that patients suffering with long COVID had a deficiency in magnesium and 25-hydroxyvitamin D which correlated with the number of associated clinical manifestations.

Reply to Scarpati, G.; Piazza, O. Comment on "Guerrero-Romero et al. Magnesium-to-Calcium Ratio and Mortality from COVID-19. Nutrients 2022, 14, 1686".

We thank Dr. Scarpati and Dr. Piazza for their interest and comments [...].

Inhibitory effect of Mexican oregano (Lippia graveolens Kunth) extracts on digestive enzymes in vitro, and beneficial impact on carbohydrates and lipids absorption in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Although Mexican oregano inhibits digestive enzymes in vitro its effect on the absorption of carbohydrates and lipids in vivo has not been addressed. AIM OF THE STUDY: Assess the effect of Mexican oregano (Lippia graveolens Kunth) on carbohydrates and lipids absorption in vivo. The antioxidant activity also was investigated. MATERIALS AND METHODS: Enzymatic inhibitory action of lipase, α-amylase, and α-glucosidase was evaluated in vitro. Oral lipid (OLTT) and starch tolerance tests (OSTT) were conducted with L. graveolens acetone (O-A) and ethanol (O-E) extracts (at 102 mg/kg body weight equivalent to a 1 g human doses) in male Wistar rats. The antioxidant activity was evaluated through inhibition of lipid peroxidation and scavenging radical. RESULTS: Both extracts exhibited higher inhibitory median concentration (IC50) of lipase activity (1.9 µg/µL for O-E and 1.8 µg/µL for O-A) than the positive control (Orlistat) (0.07 µg/µL). The IC50 of α-amylase was higher (41.8 µg/µL for O-E and 25.2 µg/µL for O-A) than the Acarbose (2.5 µg/µL); while α-glucosidase results showed not statistically differences between groups (∼1.7 µg/µL). The OLTT results showed that both extracts significantly reduced serum triglycerides (∼147 mg/dL for O-E and ∼155 mg/dL for O-A) as compared with negative control group (only lipid load). In the OSTT, glucose levels showed a significant decrease (∼31 mg/dL for O-E and ∼17 mg/dL for O-A) than the negative control group (only starch load). About in vitro antioxidant evaluation, not statistically differences between extracts and positive control (Trolox) were observed for scavenged free radicals (∼2.0 µg/µL); whereas O-A inhibited lipid peroxidation similar to the Trolox (∼0.8 µg/µL IC50). The main chemical composition of both extracts was coumaric acid, luteolin, rutinoside, naringenin, and carvacrol. CONCLUSIONS: Both extracts reduce lipid absorption; whereas O-E decreases carbohydrate absorption in vivo. Both extracts inhibit lipid peroxidation and scavenging free radicals in vitro.

Magnesium-to-Calcium Ratio and Mortality from COVID-19.

Obesity, type 2 diabetes, arterial hypertension, decrease in immune response, cytokine storm, endothelial dysfunction, and arrhythmias, which are frequent in COVID-19 patients, are associated with hypomagnesemia. Given that cellular influx and efflux of magnesium and calcium involve the same transporters, we aimed to evaluate the association of serum magnesium-to-calcium ratio with mortality from severe COVID-19. The clinical and laboratory data of 1064 patients, aged 60.3 ± 15.7 years, and hospitalized by COVID-19 from March 2020 to July 2021 were analyzed. The data of 554 (52%) patients discharged per death were compared with the data of 510 (48%) patients discharged per recovery. The ROC curve showed that the best cut-off point of the magnesium-to-calcium ratio for identifying individuals at high risk of mortality from COVID-19 was 0.20. The sensitivity and specificity were 83% and 24%. The adjusted multivariate regression model showed that the odds ratio between the magnesium-to-calcium ratio ≤0.20 and discharge per death from COVID-19 was 6.93 (95%CI 1.6-29.1) in the whole population, 4.93 (95%CI 1.4-19.1, p = 0.003) in men, and 3.93 (95%CI 1.6-9.3) in women. In conclusion, our results show that a magnesium-to-calcium ratio ≤0.20 is strongly associated with mortality in patients with severe COVID-19.

Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dL in normal weight full-term healthy newborns / Polimorfismos 1304 G > A y 292 C > T del gen placentario SLC38A4 y su asociación con glucosa > 95 mg/dL en recién nacidos a término, sanos y con peso normal al nacimiento

Abstract Background: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. Methods: We conducted a case–control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. Results: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). Conclusions: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

Resumen Introducción: El gen SLC38A4 codifica la proteína SNAT4, que se ha relacionado con alteraciones en el metabolismo de la glucosa en los humanos. El objetivo de este estudio fue determinar si los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se asocian con concentraciones de glucosa > 95 mg/dL en recién nacidos a término Métodos: Se llevó a cabo un estudio de casos y controles con 50 recién nacidos a término, sanos, con peso normal al nacimiento. Los grupos se definieron de acuerdo con las concentraciones de glucosa: > 95 mg/dL (casos; n = 13) y < 95 mg/dL (controles; n = 37). Los polimorfismos 1304 G > A y 292 C > T del gen SLC38A4 se genotipificaron por qPCR utilizando ADN de la placenta. La asociación entre los polimorfismos y la concentración de glucosa > 95 mg/dL se estableció mediante la estimación de la razón de momios (RM) en un análisis múltiple de regresión logística. Resultados: No se observaron diferencias estadísticamente significativas para la edad gestacional y el peso al nacer entre los grupos de estudio. El modelo homeostático para evaluar la resistencia a la insulina (HOMA-IR) fue significativamente más alto en los recién nacidos del grupo de casos que en el grupo control (p < 0.0005). La RM mostró asociación significativa entre el polimorfismo de nucleótido único (SNP) 292 C > T del gen SLC38A4 y la concentración de glucosa > 95 mg/dL (RM: 7.78; p = 0.024); el SNP 1304 G > A no mostró asociación significativa (RM: 1.46; p = 0.77). Conclusiones: Los resultados de este estudio sugieren que el SNP 292 C > T del gen SLC38A4 se asocia con concentraciones de glucosa > 95 mg/dL en recién nacidos a término.

Placental SLC38A4 gene polymorphisms 1304 G > A and 292 C > T, and their association with glucose > 95 mg/dl in normal weight full-term healthy newborns.

BACKGROUND: The SLC38A4 gene encodes for the SNAT4 protein, which has been related to glucose metabolic alterations in human newborns. This study aimed to determine whether the 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene are associated with the presence of glucose levels > 95 mg/dL in normal weight full-term healthy newborns. METHODS: We conducted a case-control study and analyzed 50 normal weight full-term healthy newborns. Groups were defined based on glucose levels: > 95 mg/dL (cases; n = 13) and < 95 mg/dL (controls; n = 37). The 1304 G > A and 292 C > T polymorphisms of the SLC38A4 gene were determined through quantitative polymerase chain reaction using placental DNA. The association between polymorphism and glucose levels > 95 mg/dL was established using multivariate logistic regression analysis. RESULTS: No significant differences were observed either for gestational age or body weight at birth between groups. In the case group, newborns showed significantly higher homeostatic model assessment for insulin resistance than those in the control group (p < 0.0005). The odds ratio (OR) between the SLC38A4 gene 292 C > T single-nucleotide polymorphism (SNP) and glucose levels > 95 mg/dL was 7.78 (p = 0.024), whereas no significant association was found for the 1304 G > A SNP (OR 1.46; p = 0.77). CONCLUSIONS: Our results suggest that the SLC38A4 gene 292 C > T SNP is associated with glucose levels > 95 mg/dL in normal weight full-term healthy newborns.

The triglycerides and glucose index is strongly associated with hepatic steatosis in children with overweight or obesity.

Given the worldwide increase prevalence of overweight, obesity, and nonalcoholic fatty liver disease (NAFLD), the objective of this study was to evaluate whether the triglycerides and glucose (TyG) index is associated with hepatic steatosis in children with overweight or obesity. Apparently healthy children aged 5­17 years were included and allocated into the groups with and without hepatic steatosis. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)]/2. Hepatic steatosis was diagnosed by ultrasonography. A total of 177 children, 66 (37.3%) girls and 111 (62.7%) boys, were included in the study. According to the hepatic ultrasonography, they were allocated into the groups with (n = 100) and without (n = 77) hepatic steatosis. The adjusted analysis by gender, body mass index, and waist circumference revealed that HDL-C (OR 0.96; 95% CI: 0.93-0.99), triglycerides (OR 1.005; 95% CI: 1.001-1.009), AST (OR 1.03; 95% CI: 1.008-1.07), ALT (OR 1.03; 95% CI: 1.01-1.05), and TyG index (OR 4.07; 95% CI: 1.26-13.15) remained associated with hepatic steatosis.Conclusion: Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight and obesity. What is known: • The triglycerides and glucose (TyG) index is effective in predicting high risk for incident nonalcoholic fatty liver disease (NAFLD) in adults. What is new: • Compared to other biochemical markers, the TyG index is highly associated with the presence of fatty liver in children with overweight or obesity. • The triglycerides and glucose index may be a useful tool to detect children at high risk of fatty liver.

Association of the 5HTTLPR Polymorphism with Obesity in Mexican Women with High Native American Ancestry.

Aims: The 5HTT gene has been associated with obesity; this study aimed to determine the association between L- and S-alleles at the 5HTTLPR polymorphism with obesity in indigenous Mexican populations. Materials and Methods: A total of 362 individuals, 289 belonging to eight Native American (NA) groups; 40 Mexican mestizos; and 33 Caucasian Mennonites were enrolled in a cross-sectional study. High (≥90%) and low (<90%) NA ancestry was molecularly determined. A body mass index >30 kg/m2 was considered as obese. The L- and S-alleles of the 5HTTLPR locus were identified by PCR; the association between alleles and obesity was performed by logistic regression analysis. Results: A significantly lower prevalence of obesity (35%) was observed in participants from communities with high NA ancestry (p < 0.005). Under a dominant heritance model the L-allele was associated with obesity in women with high NA ancestry (odds ratio [OR] 7.27; 95% confidence interval [CI] 1.6-32.5; p = 0.009) but not in women with low NA ancestry (OR 0.83; 95% CI 0.3-2.2; p = 0.71); no association was observed in men. Conclusion: Our results suggest that the 5HTTLPR L-allele is a risk factor for developing obesity in Mexican women with high NA ancestry (≥90%).