Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess ...of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.
Piperlongumine (PPL) has presented a variety of important pharmacological activities. In recent pharmacokinetics studies in rats, this molecule reached 76.39% of bioavailability. Although PPL is ...present in the bloodstream, no information is found on the interaction between PPL and rat serum albumin (RSA), the most abundant protein with the function of transporting endo/exogenous molecules. In this sense, the present study elucidated the mechanism of interaction between PPL and RSA, using in conjunction spectroscopic and computational techniques. This paper shows the importance of applying inner filter correction over the entire fluorescence spectrum prior to any conclusion regarding changes in the polarity of the fluorophore microenvironment, also demonstrates the convergence of the results obtained from the treatment of fluorescence data using the area below the spectrum curve and the intensity in a single wavelength. Thermodynamic parameters revealed that PPL binds to RSA spontaneously (ΔG < 0) and the process is entropically driven. Interaction density function method (IDF) indicated that PPL accessed two cooperative sites in RSA, with moderate binding constants (2.3 × 10
M
and 1.3 × 10
M
). The molecular docking described the microenvironment of the interaction sites, rich in apolar residues. The stability of the RSA-PPL complex was checked by molecular dynamics.
Studies that describe metastases to the gastrointestinal (GI) tract are restricted to small case series. An increase in the frequency of this condition is expected, so it would be useful to better ...characterize the endoscopic aspects of metastasis to the GI tract. The aims of this study were to describe the frequency and endoscopic features of the lesions, and to analyze the survival rate after diagnosis of metastasis.
This was a retrospective, single-center, observational study, conducted between 2009 and 2017. Patients with metastasis to the GI tract were included.
95 patients were included. Melanoma (25.3 %), lung (15.8 %), and breast (14.7 %) were the most frequent primary tumors. The most common endoscopic presentation was a solitary, ulcerated lesion in the gastric body. Conventional biopsy was diagnostic in 98.9 % of the cases. The mean and median survival rates were 13.3 months (95 % confidence interval CI 8.2 - 18.3) and 4.7 months (95 %CI 3.7 - 5.6), respectively. Palliative treatment with chemo- and/or radiotherapy after the diagnosis of the metastasis was related to a higher survival rate.
Melanoma, lung, and breast cancer were the most common primary tumors to metastasize to the GI tract. The endoscopic features could not predict the primary site of the tumor. The finding of metastasis in the GI tract is related to the final stage of the cancer disease but patients who received palliative treatment with chemo- and/or radiotherapy after diagnosis of GI metastasis had higher survival rates.
Purpose
Maternal obesity can program the offspring, increasing the risk of overweight and obesity in adult life. Guarana (
Paullinia cupana
) is a Brazilian plant that has weight-reducing effects. ...Thus, this study aimed to evaluate the effects of Guarana on metabolic and inflammatory parameters in mice programmed by maternal obesity.
Methods
Swiss female mice were divided into two groups: control and high fat (HF), who received a standard diet or a high-fat diet (HFD), respectively, for 8 weeks prior to mating, gestation, and lactation. After post-natal day (PN) 21, the offspring of the HF group were subdivided into three groups: HF without treatment; HF early treatment, offspring treated with Guarana (1 g/kg bodyweight) in PN25–PN30; HF late treatment, offspring treated with Guarana (1 g/kg bodyweight) in PN65–PN75. Basal energy expenditure, the lipid profile and fasting glucose levels were determined. Body composition was evaluated by dissecting adipose tissue depots. Gene expression was analyzed using real-time PCR.
Results
During mating, the weight of HF females increased; after lactation, their adipose tissue depots and fasting glycemic levels also increased. The offspring of the HF group showed an increased body weight at PN21. At PN80, in the mice treated with Guarana (with both treatments),
V
O
2
and energy expenditure increased, adipose tissue depots decreased, and the expression of leptin, IL-6, TNF-α, and MCP-1 decreased compared with that in the HF group.
Conclusions
Guarana treatment at both stages of life reversed some of the alterations developed by the offspring of HF animals in adult life.
Background
Neoadjuvant chemoradiotherapy (nCRxt) followed by radical surgery is the optimal treatment for advanced rectal adenocarcinoma. Patients with clinical complete response (cCR) may be ...followed closely without immediate surgery. Probe-based confocal laser endomicroscopy (pCLE) is a real-time in vivo method that allows acquisition of optical biopsies with 1000 times magnification, evaluating both epithelial and vascular patterns.
Aim
To evaluate the role of pCLE in the diagnosis of cCR after nCRxt for advanced rectal adenocarcinoma.
Methods
pCLE was performed in 47 patients with locally advanced rectal adenocarcinoma (T3/T4, or N+) who underwent nCRxt (5-fluorouracil, 5040 cGy).
Results
Twenty-seven (57.5%) patients were men, and the mean age was 62.8 years. Thirty-seven had partial response confirmed by pCLE. Ten (21.3%) patients had good endoscopic response and presented small ulcer (
n
= 5) or residual scar (
n
= 5). After nCRxt, the essential features to differentiate malignancy from post-radiation alterations at pCLE were the presence of irregular crypts, budding, back-to-back glands, cribriform pattern, increased vessel/crypt ratio, and fluorescein leakage. A scoring system was created considering these epithelial and vascular features, with high accuracy for differentiating patients with complete response from those with residual neoplasia (
p
< 0.00001). pCLE sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 71.4%, 95.2%, 100%, and 95.7%, respectively.
Conclusions
(1) pCLE evaluation of epithelial and vascular features may improve the diagnosis of cCR and may alter patient management; (2) pCLE might be valuable for identifying patients with advanced rectal cancer who will benefit from watch and wait strategy, avoiding immediate surgical treatment.
The Amazonian indigenous peoples depend on natural resources to live, but human activities' growing impacts threaten their health and livelihoods. Our objectives were to present the principal results ...of an integrated and multidisciplinary analysis of the health parameters and assess the mercury (Hg) exposure levels in indigenous populations in the Brazilian Amazon. We carried out a cross-sectional study based on a census of three Munduruku indigenous villages (
and
), located in the
Indigenous Land, between 29 October and 9 November 2019. The investigation included: (i) sociodemographic characterization of the participants; (ii) health assessment; (iii) genetic polymorphism analysis; (iv) hair mercury determination; and (v) fish mercury determination. We used the logistic regression model with conditional Prevalence Ratio (PR), with the respective 95% confidence intervals (CI95%) to explore factors associated with mercury exposure levels ≥6.0 µg/g. A total of 200 participants were interviewed. Mercury levels (197 hair samples) ranged from 1.4 to 23.9 μg/g, with significant differences between the villages (Kruskal-Wallis test: 19.9;
-value < 0.001). On average, the general prevalence of Hg exposure ≥ 6.0 µg/g was 57.9%. For participants ≥12 years old, the Hg exposure ≥6.0 µg/g showed associated with no regular income (PR: 1.3; CI95%: 1.0-1.8), high blood pressure (PR: 1.6; CI95%: 1.3-2.1) and was more prominent in
village (PR: 1.8; CI95%: 1.3-2.3). For women of childbearing age, the Hg exposure ≥6.0 µg/g was associated with high blood pressure (PR: 1.9; CI95%: 1.2-2.3), with pregnancy (PR: 1.5; CI95%: 1.0-2.1) and was more prominent among residents in
(PR: 1.9; CI95%: 1.0-3.4) and
(PR: 2.5; CI95%: 1.4-4.4) villages. Our findings suggest that chronic mercury exposure causes harmful effects to the studied indigenous communities, especially considering vulnerable groups of the population, such as women of childbearing age. Lastly, we propose to stop the illegal mining in these areas and develop a risk management plan that aims to ensure the health, livelihoods, and human rights of the indigenous people from Amazon Basin.
Wound healing is characterized by a systemic and complex process of cellular and molecular activities. Dipotassium Glycyrrhizinate (DPG), a side product derived from glycyrrhizic acid, has several ...biological effects, such as being antiallergic, antioxidant, antibacterial, antiviral, gastroprotective, antitumoral, and anti-inflammatory. This study aimed to evaluate the anti-inflammatory effect of topical DPG on the healing of cutaneous wounds by secondary intention in an in vivo experimental model. Twenty-four male Wistar rats were used in the experiment, and were randomly divided into six groups of four. Circular excisions were performed and topically treated for 14 days after wound induction. Macroscopic and histopathological analyses were performed. Gene expression was evaluated by real-time qPCR. Our results showed that treatment with DPG caused a decrease in the inflammatory exudate as well as an absence of active hyperemia. Increases in granulation tissue, tissue reepithelization, and total collagen were also observed. Furthermore, DPG treatment reduced the expression of pro-inflammatory cytokines (
,
,
,
,
, and
) while increasing the expression of
, demonstrating anti-inflammatory effects across all three treatment periods. Based on our results, we conclude that DPG attenuates the inflammatory process by promoting skin wound healing through the modulation of distinct mechanisms and signaling pathways, including anti-inflammatory ones. This involves modulation of the expression of pro- and anti-inflammatory cytokine expression; promotion of new granulation tissue; angiogenesis; and tissue re-epithelialization, all of which contribute to tissue remodeling.
Guarana (
) is a plant originated in Brazil that presents a beneficial effect on body weight control and metabolic alterations. The aim of this study was to evaluate the effects of guarana on genes ...and miRNAs related to adipogenesis in 3T3L1 cells. The anti-adipogenic effect of guarana was evaluated by Oil Red-O staining. Gene and miRNA expression levels were determined by real time PCR. The Cebpα and β-catenin nuclear translocation were evaluated using immunocytochemistry. Our data indicated that the triglyceride-reducing effect of guarana was dose-dependent from 100 to 300 µg/mL (-12%, -20%, -24% and -40%, respectively,
< 0.0001). An up-regulation of the anti-adipogenic genes
,
,
,
and
and a down-regulation of pro-adipogenic genes
,
and
were also observed. Furthermore, guarana repressed mmu-miR-27b-3p, mmu-miR-34b-5p and mmu-miR-760-5p, that contributed for up-regulation of their molecular targets
,
and
. Additionally, cells treated with guarana presented an increase on β-catenin nuclear translocation (
< 0.0018). In summary, our data indicate that guarana has an anti-adipogenic potential due to its ability to modulate miRNAs and genes related to this process. Together our data demonstrate the important role of guarana as a putative therapeutic agent.
In the aging process, physiological decline occurs, posing a substantial threat to the physical and mental well-being of the elderly and contributing to the onset of age-related diseases. While ...traditional perspectives considered the maintenance of life as influenced by a myriad of factors, including environmental, genetic, epigenetic, and lifestyle elements such as exercise and diet, the pivotal role of symbiotic microorganisms had been understated. Presently, it is acknowledged that the intestinal microbiota plays a profound role in overall health by signaling to both the central and peripheral nervous systems, as well as other distant organs. Disruption in this bidirectional communication between bacteria and the host results in dysbiosis, fostering the development of various diseases, including neurological disorders, cardiovascular diseases, and cancer. This review aims to delve into the intricate biological mechanisms underpinning dysbiosis associated with aging and the clinical ramifications of such dysregulation. Furthermore, we aspire to explore bioactive compounds endowed with functional properties capable of modulating and restoring balance in this aging-related dysbiotic process through epigenetics alterations.
Background and Aims Self-expandable metallic stents are considered the best palliative treatment of dysphagia for patients with advanced esophageal cancer. Adverse events (AEs) are a major concern, ...especially in patients with better prognosis and longer survival. The present study aimed to evaluate the AEs of patients who survived longer than 6 months with esophageal stents in place. Methods This is a retrospective analysis of a prospectively collected database including all patients submitted to esophageal stent placement for the palliation of malignant diseases during the period from February 2009 to February 2014 at a tertiary care academic center who had stents longer than 6 months. Results Sixty-three patients were included. Mean follow-up was 10.7 months. Clinical success was achieved in all patients, and the median stent patency was 7.1 months. AEs occurred in 40 patients (63.5%), totaling 62 AEs (mean, 1.5 AEs per patient). Endoscopic management of AEs was successful in 84.5% of cases, with a mean of 1.6 reinterventions per patient. The univariate analysis revealed that performance status, age, and post-stent radiotherapy presented a trend to higher risk of AEs. The multivariate analysis revealed that only performance status was associated with AEs ( P = .025; hazard ratio, 4.1). Conclusions AEs are common in patients with long-term esophageal stenting for malignancy. However, AEs were not related to higher mortality rate, and most AEs could be successfully managed by endoscopy. Only performance status was a risk factor for AEs. Our data suggest that metallic stenting is a valid option for the treatment of malignant esophageal conditions, even when survival longer than 6 months is expected.
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