Prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros / Smoking prevalence and lung cancer morbimortality in Brazilian states / Prevalencia del tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños

Introdução: O câncer de pulmão é uma doença grave, sendo a segunda maior causa de morte em todo o mundo, entretanto, em alguns países desenvolvidos, tornou-se já a primeira causa de morte. Cerca de 90% dos casos de neoplasia pulmonares são causados pela inalação da fumaça do cigarro. Objetivo: Correlacionar a prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, além de demonstrar a associação destes com sexo e faixa etária. Métodos: Estudo de caráter ecológico acerca da prevalência de tabagismo e morbimortalidade por câncer de pulmão nos estados brasileiros, nos períodos de 2013 e 2019, dividida por sexo e faixa etária. Foram utilizados bancos de coleta de dados como o Tabnet e Pesquisa Nacional de Saúde. Resultados: As maiores taxas de mortalidade e internações hospitalares foram do público masculino, em 2013, com taxa de 2,7 e 10, respectivamente, e em 2019 com 3,3 e 11,9, respectivamente. Ademais, a maior prevalência de tabagismo foi encontrada nos homens; entretanto seu índice tem caído, enquanto a quantidade de mulheres tabagistas tem aumentado. A Região Sul demonstrou maiores números de mortalidade em ambos os períodos estudados, com taxas de 4,9 e 5,8 por 100 mil habitantes, e morbidade hospitalar com 19,9 e 23,5 por 100 mil habitantes. Já a Região Norte se configurou com as menores prevalências: em 2013 apresentou taxa de óbito por câncer de pulmão de 1,0 e morbidade hospitalar de 3,5/100 mil habitantes, em 2019 apresentou taxa de mortalidade de 4,6 e internações de 1,6/100 mil habitantes. Os coeficientes de correlação de morbidade hospitalar e prevalência de tabagismo foram R2=0,0628, r=0,251 e p=0,042, enquanto os de mortalidade e prevalência de tabagismo foram R2=0,0337, r=0,183 e p=0,140. Conclusões: Na presente pesquisa, pode-se inferir que houve associação positiva na comparação entre taxa de morbidade hospitalar e prevalência de tabagismo; em contrapartida, não foi possível observar associação positiva na correlação da taxa de mortalidade por câncer de pulmão e prevalência de tabagismo.

Introduction: Lung cancer is a serious disease, being the second leading cause of death worldwide. Moreover, in some developed countries, it has already become the leading cause of death. About 90% of lung cancer cases are caused by cigarette smoking. Objective: To correlate the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states, and to demonstrate their association with sex and age group as well. Methods: An ecological study on the prevalence of smoking and lung cancer morbidity and mortality in Brazilian states between 2013 and 2019, divided by sex and age group. The data collection databases Tabnet and National Health Survey were used. Results: The highest rates of mortality and hospital admissions were among men, in 2013 with a rate of 2.7 and 10, respectively, and in 2019 with 3.3 and 11.9, respectively. In addition, the highest prevalence of smoking was found in men, but this rate has fallen, while the number of women smokers has increased. The South region showed higher mortality rates in both periods studied, with rates of 4.9 and 5.8 per 100,000 inhabitants, and hospital morbidity with 19.9 and 23.5 per 100,000 inhabitants. The North region had the lowest prevalence, where in 2013, it had a death rate from lung cancer of 1.0 and hospital morbidity of 3.5/100 thousand inhabitants, and where in 2019, it had a mortality rate of 4.6 and hospitalizations of 1.6/100 thousand inhabitants. The correlation coefficients for hospital morbidity and smoking prevalence were R2=0.0628, r=0.251 and p=0.042, while for mortality and smoking prevalence, these were R2=0.0337, r=0.183 and p=0.140. Conclusions: In the present study, it can be inferred that there was a positive association between hospital morbidity rate and prevalence of smoking, while it was not possible to observe a correlation between lung cancer mortality rate and prevalence of smoking.

Introducción: El cáncer de pulmón es una enfermedad grave, siendo la segunda causa de muerte en todo el mundo, sin embargo, en algunos países desarrollados, ya se ha convertido en la primera causa de muerte. Alrededor del 90% de los casos de neoplasias pulmonares están causados por la inhalación del humo del cigarrillo. Objetivo: Correlacionar la prevalencia de tabaquismo y la morbimortalidad por cáncer de pulmón en los estados brasileños, además de demostrar la asociación de estos con el género y el grupo de edad. Métodos: estudio ecológico sobre la prevalencia de tabaquismo y morbimortalidad por cáncer de pulmón en los estados brasileños, dentro de los períodos 2013 y 2019, divididos por sexo y grupo de edad. Se utilizaron bancos de recogida de datos como Tabnet y la Encuesta Nacional de Salud. Resultados: las mayores tasas de mortalidad e ingresos hospitalarios se dieron en el público masculino, en 2013 con una tasa de 2,7 y 10, respectivamente, y en 2019 con 3,3 y 11,9, respectivamente. Además, la mayor prevalencia del tabaquismo se encontró en los hombres, sin embargo, su tasa ha disminuido, mientras que la cantidad de mujeres fumadoras ha aumentado. La región Sur presentó cifras más altas de mortalidad en ambos periodos estudiados, con tasas de 4,9 y 5,8 por 100.000 habitantes, y de morbilidad hospitalaria con 19,9 y 23,5 por 100.000 habitantes. Mientras que la región Norte se configuró con las prevalencias más bajas, en 2013 presentó una tasa de mortalidad por cáncer de pulmón de 1,0 y una morbilidad hospitalaria de 3,5/100.000 habitantes, en 2019 presentó una tasa de mortalidad de 4,6 y hospitalizaciones de 1,6/100.000 habitantes. Los coeficientes de correlación para la morbilidad hospitalaria y la prevalencia del tabaquismo fueron R2=0,0628, r=0,251 y p=0,042, mientras que para la mortalidad y la prevalencia del tabaquismo fueron R2=0,0337, r=0,183 y p=0,140. Conclusiones: En la presente investigación se puede inferir que existe una asociación positiva en la comparación entre la tasa de morbilidad hospitalaria y la prevalencia de tabagismo, en contrapartida, no fue posible observar una asociación positiva en la correlación de la tasa de mortalidad por cáncer de pulmón y la prevalencia de tabagismo.

Tracking the Variations in Trace and Heavy Elements in Smoking Products Marketed in Oman and Egypt: Risk Assessment After Implementation of Constraining Protocols.

Tobacco smoking is becoming one of the major worldwide concerns regarding environmental pollution as well as health threats. In 2005, the World Health Organization (WHO) released the Framework Convention On Tobacco Control (FCTC), which outlined protocols for controlling tobacco products. Oman was one of the leading countries to follow these protocols; however, Egypt has only followed these protocols recently in 2020. One of the main challenges in tobacco product control is the variation in their trace element's types and amounts from country to country owing to differences in agriculture techniques and used chemical additives. Smoking releases different toxic metal ions found in them into the air, and hence, analyzing trace amounts of metals in tobacco smoking products is becoming more critical. The proposed research aims to evaluate the current levels of 11 heavy metals (namely, As, Pb, Cd, Co, Cr, Be, Ba, Mn, Ni, Fe, and Hg) in 22 tobacco products available in Egypt and Oman using inductively coupled plasma optical emission spectroscopy and a direct mercury analyzer. Although some elements such as Be, Co, and Cd were absent, the positive detection of As and Pb and the levels of Ba, Cr, and Ni are still alarming, especially for heavy smokers. The obtained results were then statistically related to previously published data in 2017 to explore the effectiveness of implementing the FCTC protocols within the Egyptian market. The outcomes suggested a positive impact of FCTC protocol implementation in Egypt, besides the lower levels of elemental content for Omani products compared to the Egyptian market.

The antiglycation potential of H1 receptor antagonists - in vitro studies in bovine serum albumin model and in silico molecular docking analyses.

The H1 receptor belongs to the family of rhodopsin-like G-protein-coupled receptors activated by the biogenic amine histamine. H1 receptor antagonists are widely used in the treatment of allergies. However, these drugs could have a much broader spectrum of activity, including hypoglycemic effects, which can broaden the spectrum of their use. The aim of the study was to evaluate the antiglycation potential of twelve H1 receptor antagonists (diphenhydramine, antazoline, promethazine, ketotifen, clemastine, pheniramine, cetirizine, levocetirizine, bilastine, fexofenadine, desloratadine, and loratadine). Bovine serum albumin (BSA) was glycated with sugars (glucose, fructose, galactose, and ribose) and aldehydes (glyoxal and methylglyoxal) in the presence of H1 blockers. The tested substances did not induce a significant decrease in the content of albumin glycation end-products, and the inhibition rate of glycoxidation was not influenced by the chemical structure or generation of H1 blockers. None of the tested H1 receptor antagonists exhibited strong antiglycation activity. Antiglycemic potential of H1 blockers could be attributed to their antioxidant and anti-inflammatory activity, as well as their effects on carbohydrate metabolism/metabolic balance at the systemic level.

Coupling of a streamlined solid-liquid extraction protocol with LC-ESI-MS/MS for the regular oversight of illegal bromate additive use: An accurate and sensitive determination method in preliminary and bakery products.

A reliable solid-liquid extraction protocol coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry in the negative-ion mode was developed and validated for illegal bromate determination in preliminary and bakery products. Crude and dried-treated samples were directly extracted with acetonitrile-water (4:1, v/v). Bromate was determined using a Phenomenex Synergi™ Polar reversed-phase column and MS/MS under multiple reaction monitoring. The chosen solvent efficiently extracted bromate with all applied extraction-assisting techniques (p > 0.05). Although this assay avoids cleanup procedures, matrix effect of <-11% was achieved. Rapid bromate separation in only 8 min was attained by a reversed-phase column. In both commodities, linearity range, R2, recovery%, repeatability, intermediate precision, LOD and LOQ results were 0.05-100 ng mL-1, >0.9999, 88.6-103%, 2.93-9.80% and 9.64-10.10%, 0.015 µg kg-1 and 0.05 µg kg-1, respectively. Out of 288 tested real samples, 13.9% of violations were observed. This high-sensitivity protocol offers effective oversight and consumer protection.

Re-discovery of MS-347a as a fungicide candidate through a new drug discovery platform with a multidrug-sensitive Saccharomyces cerevisiae screening system and the introduction of a global secondary metabolism regulator, laeA gene.

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of ten-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery.

Connection of spectral pattern of carbohydrate molecular structure to alteration of nutritional properties of by-products from coffee processing affected by microorganism fermentation.

Objective: The objective of this study was to determine internal structure spectral profile of by-products from coffee processing that were affected by added-microorganism fermentation duration in relation to truly absorbed feed nutrient supply in ruminant system. Methods: The by-products from coffee processing were fermented using commercial fermentation product, consisting of various microorganisms: for 0 (control), 7, 14, 21, and 28 days. In this study, the association and correlation of carbohydrate-related spectral profiles with chemical and nutritional properties (chemical composition, total digestible nutrient, bioenergy values, carbohydrate sub-fractions and predicted degradation and digestion parameters as well as milk value of feed. The vibrational spectra of coffee by-products samples after fermentation for 0 (control), 7, 14, 21, and 28 days were determined using a JASCO FT/IR-4200 spectroscopy coupled with accessory of Attenuated total reflectance (ATR). The molecular spectral analyses with univariate approach were conducted with the OMNIC 7.3 software. Results: Molecular spectral analysis parameters in fermented and non-fermented by-products from coffee processing included Structural carbohydrate, Cellulosic compounds, Non-structural carbohydrates, Lignin compound, CH-bending, structural carbohydrate peak1, Structural carbohydrate peak2, Structural carbohydrate peak3, Hemicellulosic compound, Non-structural carbohydrate peak1, non-structural carbohydrate peak2, non-structural carbohydrate peak3. The study results show that added-microorganism fermentation induced chemical and nutritional changes of coffee by-products including carbohydrate chemical composition profiles, bioenergy value, feed milk value, carbohydrate subfractions, estimated degradable and undegradable fractions in the rumen, and intestinal digested nutrient supply in ruminant system. Conclusion: In conclusion, carbohydrate nutrition value changes by added-microorganism fermentation duration were in an agreement with the change of their spectral profile in the coffee by-products. The studies show that the vibrational ATR-FT/IR spectroscopic technique could be applied as a rapid analytical tool to evaluate fermented by-products and connect with truly digestible carbohydrate supply in ruminant system.

Synthesis of C3-epi-virenose and anomerically activated derivatives.

A 9-step synthetic route to a protected form of the C3-epimer of virenose from D-fucose is described. C3-epi-virenose is the carbohydrate unit of the bioactive polyketide elsamicin B and part of the carbohydrate unit of elsamicin A. The developed route enabled preparation of anomerically activated forms of this unique C6-deoxy sugar, including derivatives with 1-acetyl, 1-acetylthio, 1-trichloroacetimidate, 1-bromo, and 1-fluoro substituents.

Fabrication of textured functional ingredient based on apple: Sesame by-product.

The search for new sources of fortified components from low-cost and sustainable sources has become a trend in the last decade. Food byproducts containing valuable bioactive compounds such as dietary fiber, protein, and phytochemicals are being used as substrates for obtaining beneficial components that can promote health. Extrusion is an efficient technology for converting food by-products into nutrient-rich food ingredients. The objective of this work was to optimize the extrusion process to obtain the best combination of moisture content (14, 18 and 22%) and screw speed (SS) (120,150 and180 rpm), apple pomace (AP): semi-defatted sesame cake (SDSC) blends (25:75, 50:50 and 75:25 w/w) to fabricate textured functional ingredients (TFI) with high values of expansion ratio (ER), water absorption index (WAI), brightness level, total phenolic compounds (TPC) and antioxidant activity (AA) and lower hardness based on a central composite design. The optimal treatment was determined at 176 rpm SS, 18% moisture content and a ratio of (75:25) AP: SDSC. The desirability value has indicated an appropriate match between the predicted and the observed response. TFI exhibited higher soluble dietary fiber fraction (WAI) values and lower plate count values during 30 days of storage compared to the unprocessed by-product, suggesting that TFI could be successfully used for the manufacture of innovative, high quality products such as porridge, beverages, cookies, soups and others that could provide health benefits based on the values obtained.

Replacement of nitrates and nitrites in meat-derived foods through the utilization of coagulase-negative staphylococci: A review.

Nitrates and nitrites, which are synthetic additives, are traditionally used as curing agents in meat-based products. These synthetic additives are employed in the preparation of fermented meat foods to improve quality characteristics and microbiological safety, develop distinct flavours and red-colour stability, and counteract lipid oxidation. Nitrites also display significant bacteriostatic and bactericidal action against spoilage microorganisms and foodborne pathogens (such as Clostridium botulinum and Listeria monocytogenes). However, meat curing is currently under scrutiny because of its links to cardiovascular diseases and colorectal cancer. Based on the current literature, this review provides recent scientific evidence on the potential utilisation of coagulase-negative staphylococci (CNS) as nitrate and nitrite substitutes in meat-based foods. Indeed, CNS are reported to reproduce the characteristic red pigmentation and maintain the typical high-quality traits of cured-meats, thanks to their arginine degradation pathway, thus providing the nitrite-related desirable attributes in cured meat. The alternative strategy, still based on the NOS pathway, consisting of supplementing meat with arginine to release nitric oxide (NO) and obtain a meat characterised by the desired pinkish-red colour, is also reviewed. Exploiting NOS-positive CNS strains seems particularly challenging because of CNS technological adaptation and the oxygen dependency of the NOS reaction; however, this exploitation could represent a turning point in replacing nitrates and nitrites in meat foods.

Nutritional profile of plant-based dairy alternatives in the Swedish market.

The market for plant-based dairy alternatives is growing; therefore, focusing on the nutritional quality of these products is important. This study evaluates the nutritional profile of plant-based alternatives to milk, yoghurt, cheese, cream, ice cream and fat spread in the Swedish market and compares them to corresponding dairy products. The nutritional quality of organic vs non-organic and plain vs flavoured plant-based milk and yoghurt alternatives was also assessed. Nutritional data for 222 plant-based dairy alternatives were collected from the manufacturers' websites, and data for corresponding dairy products were obtained from the Swedish Food Composition Database. Plant-based dairy alternatives had higher fibre content than dairy products, while their protein content was lower, except for soy-based products. The saturated fat content of plant-based dairy alternatives was similar to or lower than dairy products, except for coconut-based yoghurt and plant-fat-based cheese. Their energy content was also similar to or lower than dairy products, except for coconut-based yoghurt, plant-based fat spread and plant-based ice cream, which contained higher energy than yoghurt, blended margarine, and ice cream, respectively. The micronutrient fortification was mainly in plant-based milk, yoghurt, and cheese alternatives; thus, compared to dairy, they had similar or higher vitamins D, B2, and B12 (except in plant-based milk alternatives), calcium and iodine content. Furthermore, organic plant-based milk and yoghurt alternatives had a lower micronutrient content (e.g., vitamins B2 and B12, iodine and calcium) except for vitamin D than non-organic varieties. Flavoured plant-based milk and yoghurt alternatives were higher in energy and total sugar than plain varieties. In summary, plant-based dairy alternatives have nutritional strengths and weaknesses compared to dairy products that should be considered when replacing dairy.

Machine learning-based identification of novel hub genes associated with oxidative stress in lupus nephritis: implications for diagnosis and therapeutic targets.

BACKGROUND: Lupus nephritis (LN) is a complication of SLE characterised by immune dysfunction and oxidative stress (OS). Limited options exist for LN. We aimed to identify LN-related OS, highlighting the need for non-invasive diagnostic and therapeutic approaches. METHODS: LN-differentially expressed genes (DEGs) were extracted from Gene Expression Omnibus datasets (GSE32591, GSE112943 and GSE104948) and Molecular Signatures Database for OS-associated DEGs (OSEGs). Functional enrichment analysis was performed for OSEGs related to LN. Weighted gene co-expression network analysis identified hub genes related to OS-LN. These hub OSEGs were refined as biomarker candidates via least absolute shrinkage and selection operator. The predictive value was validated using receiver operating characteristic (ROC) curves and nomogram for LN prognosis. We evaluated LN immune cell infiltration using single-sample gene set enrichment analysis and CIBERSORT. Additionally, gene set enrichment analysis explored the functional enrichment of hub OSEGs in LN. RESULTS: The study identified four hub genes, namely STAT1, PRODH, TXN2 and SETX, associated with OS related to LN. These genes were validated for their diagnostic potential, and their involvement in LN pathogenesis was elucidated through ROC and nomogram. Additionally, alterations in immune cell composition in LN correlated with hub OSEG expression were observed. Immunohistochemical analysis reveals that the hub gene is most correlated with activated B cells and CD8 T cells. Finally, we uncovered that the enriched pathways of OSEGs were mainly involved in the PI3K-Akt pathway and the Janus kinase-signal transducer and activator of transcription pathway. CONCLUSION: These findings contribute to advancing our understanding of the complex interplay between OS, immune dysregulation and molecular pathways in LN, laying a foundation for the identification of potential diagnostic biomarkers and therapeutic targets.

Prevalence of tobacco use among cancer patients in Iran: a systematic review and meta-analysis.

BACKGROUND: The prevalence of tobacco use among various cancer types in Iran remains a significant concern, necessitating a comprehensive analysis to understand the extent and patterns of consumption. This study aimed to systematically review and analyze existing literature to delineate the prevalence of tobacco use across different cancer types in Iran, thereby providing a robust basis for future interventions and policy formulations. METHODS: Adhering to the PRISMA guidelines, we conducted a systematic review and meta-analysis of literature available in PubMed and Scopus databases. The initial search identified 351 records, out of which 44 studies were selected based on their relevance and design. These studies spanned various time frames, starting from the 2001s up until 2022, and encompassed diverse geographical locations and cancer types in Iran. To avoid bias and potential data overlap, we opted to incorporate a single comprehensive study from the Golestan Cohort, encompassing all data, while excluding 10 other studies. Our final analysis incorporated data from 34 studies, which accounted for 15,425 patients and 5,890 reported smokers. Statistical analyses were performed to calculate the overall proportion of tobacco consumption and to conduct subgroup analyses based on different variables such as cancer types, gender, geographical locations, and types of tobacco used. RESULTS: The analysis revealed a substantial prevalence of tobacco use among cancer patients in Iran, with an overall consumption rate of 43%. This rate varied significantly, ranging from 10 to 88% across individual studies. Subgroup analyses further highlighted disparities in tobacco consumption rates across different demographics, geographic areas, and cancer types. Notably, the 'ever' smokers category exhibited the highest prevalence of tobacco use. The study also identified a worrying trend of high cigarette smoking rates, along with variable consumption patterns of other forms of tobacco, including waterpipe, 'Naas', and 'Pipe'. CONCLUSIONS: This systematic review and meta-analysis underscores a significant association between tobacco consumption and various cancer types in Iran, with a prevalence rate among cancer patients being three times higher than the average Iranian population. The findings indicate substantial heterogeneity in tobacco use patterns, emphasizing the need for targeted interventions to address this pressing health issue. The study serves as a critical resource for shaping future policies and strategies aimed at curbing tobacco use and mitigating its adverse effects on cancer prevalence in Iran.

A survey of severe asthma in Canada: results from the CASCADE practice reflective program.

BACKGROUND: Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. METHODS: The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. RESULTS: The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. CONCLUSIONS: Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved.

Mixed exposure to haloacetaldehyde disinfection by-products exacerbates lipid aggregation in the liver of mice.

Haloacetaldehyde disinfection by-products (HAL-DBPs) are among the top three unregulated DBPs found in drinking water. The cytotoxicity and genotoxicity of HALs are much higher than that of the regulated trihalomethanes and haloacetic acids. Previous studies have mainly focused on the toxic effects of single HAL, with few examining the toxic effects of mixed exposures to HALs. The study aimed to observe the effects of mixed exposures of 1∼1000X the realistic level of HALs on the hepatotoxicity and lipid metabolism of C57BL/6J mice, based on the component and concentration of HALs detected in the finished water of Shanghai. Exposure to realistic levels of HALs led to a significant increase in phosphorated acetyl CoA carboxylase 1 (p-ACC1) in the hepatic de novo lipogenesis (DNL) pathway. Additionally, exposure to 100X realistic levels of HALs resulted in significant alterations to key enzymes of DNL pathway, including ACC1, fatty acid synthase (FAS), and diacylglycerol acyltransferase 2 (DGAT2), as well as key proteins of lipid disposal such as carnitine palmitoyltransferase 1 (CPT-1) and peroxisome proliferator activated receptor α (PPARα). Exposure to 1000X realistic levels of HALs significantly increased hepatic and serum triglyceride levels, as well as total cholesterol, low-density lipoprotein, alanine aminotransferase, aspartate transaminase, alkaline phosphatase, and lactate dehydrogenase levels, significantly decreased high-density lipoprotein. Meanwhile, histopathological analysis demonstrated that HALs exacerbated tissue vacuolization and inflammatory cell infiltration in mice livers, which showed the typical phenotypes of non-alcoholic fatty liver disease (NAFLD). These results suggested that the HALs mixture is a critical risk factor for NAFLD and is significantly highly toxic to C57BL/6J mice.

Analysis of GC × GC fingerprints from medicinal materials using a novel contour detection algorithm: A case of Curcuma wenyujin.

This study introduces an innovative contour detection algorithm, PeakCET, designed for rapid and efficient analysis of natural product image fingerprints using comprehensive two-dimensional gas chromatogram (GC × GC). This method innovatively combines contour edge tracking with affinity propagation (AP) clustering for peak detection in GC × GC fingerprints, the first in this field. Contour edge tracking significantly reduces false positives caused by "burr" signals, while AP clustering enhances detection accuracy in the face of false negatives. The efficacy of this approach is demonstrated using three medicinal products derived from Curcuma wenyujin. PeakCET not only performs contour detection but also employs inter-group peak matching and peak-volume percentage calculations to assess the compositional similarities and differences among various samples. Furthermore, this algorithm compares the GC × GC fingerprints of Radix/Rhizoma Curcumae Wenyujin with those of products from different botanical origins. The findings reveal that genetic and geographical factors influence the accumulation of secondary metabolites in various plant tissues. Each sample exhibits unique characteristic components alongside common ones, and variations in content may influence their therapeutic effectiveness. This research establishes a foundational data-set for the quality assessment of Curcuma products and paves the way for the application of computer vision techniques in two-dimensional (2D) fingerprint analysis of GC × GC data.

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria.

Linear nitramines (R-N(R')NO2; R' = H or alkyl) are toxic compounds, some with environmental relevance, while others are rare natural product nitramines. One of these natural product nitramines is N-nitroglycine (NNG), which is produced by some Streptomyces strains and exhibits antibiotic activity towards Gram-negative bacteria. An NNG degrading heme enzyme, called NnlA, has recently been discovered in the genome of Variovorax sp. strain JS1663 (Vs NnlA). Evidence is presented that NnlA and therefore, NNG degradation activity is widespread. To achieve this objective, we characterized and tested the NNG degradation activity of five Vs NnlA homologs originating from bacteria spanning several classes and isolated from geographically distinct locations. E. coli transformants containing all five homologs converted NNG to nitrite. Four of these five homologs were isolated and characterized. Each isolated homolog exhibited similar oligomerization and heme occupancy as Vs NnlA. Reduction of this heme was shown to be required for NnlA activity in each homolog, and each homolog degraded NNG to glyoxylate, NO2- and NH4+ in accordance with observations of Vs NnlA. It was also shown that NnlA cannot degrade the NNG analog 2-nitroaminoethanol. The combined data strongly suggest that NnlA enzymes specifically degrade NNG and are found in diverse bacteria and environments. These results imply that NNG is also produced in diverse environments and NnlA may act as a detoxification enzyme to protect bacteria from exposure to NNG.

Targeting autophagy with natural products as a potential therapeutic approach for diabetic microangiopathy.

As the quality of life improves, the incidence of diabetes mellitus and its microvascular complications (DMC) continues to increase, posing a threat to people's health and wellbeing. Given the limitations of existing treatment, there is an urgent need for novel approaches to prevent and treat DMC. Autophagy, a pivotal mechanism governing metabolic regulation in organisms, facilitates the removal of dysfunctional proteins and organelles, thereby sustaining cellular homeostasis and energy generation. Anomalous states in pancreatic ß-cells, podocytes, Müller cells, cardiomyocytes, and Schwann cells in DMC are closely linked to autophagic dysregulation. Natural products have the property of being multi-targeted and can affect autophagy and hence DMC progression in terms of nutrient perception, oxidative stress, endoplasmic reticulum stress, inflammation, and apoptosis. This review consolidates recent advancements in understanding DMC pathogenesis via autophagy and proposes novel perspectives on treating DMC by either stimulating or inhibiting autophagy using natural products.

Tapping the biosynthetic potential of marine Bacillus licheniformis LHG166, a prolific sulphated exopolysaccharide producer: structural insights, bio-prospecting its antioxidant, antifungal, antibacterial and anti-biofilm potency as a novel anti-infective lead.

The escalating global threat of antimicrobial resistance necessitates prospecting uncharted microbial biodiversity for novel therapeutic leads. This study mines the promising chemical richness of Bacillus licheniformis LHG166, a prolific exopolysaccharide (EPSR2-7.22 g/L). It comprised 5 different monosaccharides with 48.11% uronic acid, 17.40% sulfate groups, and 6.09% N-acetyl glucosamine residues. EPSR2 displayed potent antioxidant activity in DPPH and ABTS+, TAC and FRAP assays. Of all the fungi tested, the yeast Candida albicans displayed the highest susceptibility and antibiofilm inhibition. The fungi Aspergillus niger and Penicillium glabrum showed moderate EPSR2 susceptibility. In contrast, the fungi Mucor circinelloides and Trichoderma harzianum were resistant. Among G+ve tested bacteria, Enterococcus faecalis was the most susceptible, while Salmonella typhi was the most sensitive to G-ve pathogens. Encouragingly, EPSR2 predominantly demonstrated bactericidal effects against both bacterial classes based on MBC/MIC of either 1 or 2 superior Gentamicin. At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 88.30% against B. subtilis, while for G-ve antibiofilm inhibition, At 75% of MBC, EPSR2 displayed the highest anti-biofilm activity of 96.63% against Escherichia coli, Even at the lowest dose of 25% MBC, EPSR2 reduced biofilm formation by 84.13% in E. coli, 61.46% in B. subtilis. The microbial metabolite EPSR2 from Bacillus licheniformis LHG166 shows promise as an eco-friendly natural antibiotic alternative for treating infections and oxidative stress.

Identifying and costing common gaps in Central and West Africa pharmaceutical regulation.

Background: Regulatory systems strengthening is crucial for catalyzing access to safe and effective medical products and health technologies (MPHT) for all. Identifying and addressing common regulatory gaps through regional approaches could be instrumental for the newly incepted African Medicine Agency. Aims: This original study sheds light on common gaps among 10 national regulatory authorities (NRAs) and ways to address them regionally. Objectives: The study used NRA self-assessment outcomes to identify common gaps in four critical regulatory pillars and estimate the cost of addressing them from regional perspectives that aimed at raising the maturity level of regulatory institutions. Methods: A cross-sectional study, using the WHO Global Benchmarking Tool (GBT), was conducted between 2020 and 2021 with five NRAs from ECCAS and ECOWAS member states that use French and Spanish as lingua franca. Results: The 10 NRAs operated in a non-formal-to-reactive approach (ML1-2), which hinders their ability to ensure the quality of MPHT and respond appropriately to public health emergencies. Common gaps were identified in four critical regulatory pillars-good regulatory practices, preparedness for public health emergencies, quality management systems, and substandard and falsified medical products-with overall cost to address gaps estimated at US$3.3 million. Contribution: We elaborated a reproducible method to strengthen regulatory systems at a regional level to improve equitable access to assured-quality MPHT. Our bottom-up approach could be utilized by RECs to address common gaps through common efforts.

Paediatric clinical study of 3D printed personalised medicines for rare metabolic disorders.

Rare diseases are infrequent, but together they affect up to 6-10 % of the world's population, mainly children. Patients require precise doses and strict adherence to avoid metabolic or cardiac failure in some cases, which cannot be addressed in a reliable way using pharmaceutical compounding. 3D printing (3DP) is a disruptive technology that allows the real-time personalization of the dose and the modulation of the dosage form to adapt the medicine to the therapeutic needs of each patient. 3D printed chewable medicines containing amino acids (citrulline, isoleucine, valine, and isoleucine and valine combinations) were prepared in a hospital setting, and the efficacy and acceptability were evaluated in comparison to conventional compounded medicines in six children. The inclusion of new flavours (lemon, vanilla and peach) to obtain more information on patient preferences and the implementation of a mobile app to obtain patient feedback in real-time was also used. The 3D printed medicines controlled amino acid levels within target levels as well as the conventional medicines. The deviation of citrulline levels was narrower and closer within the target concentration with the chewable formulations. According to participants' responses, the chewable formulations were well accepted and can improve adherence and quality of life. For the first time, 3DP enabled two actives to be combined in the same formulation, reducing the number of administrations. This study demonstrated the benefits of preparing 3D printed personalized treatments for children diagnosed with rare metabolic disorders using a novel technology in real clinical practice.