RESUMO
PURPOSE OF REVIEW: As obesity and chronic kidney disease (CKD) remain a public health issue, we aim to elaborate on their complex relationship regarding pathogenetic mechanisms and therapeutic potential as well. The purpose of this review is to enhance our understanding of the interplay between obesity and CKD in order to timely diagnose and treat obesity-related CKD. RECENT FINDINGS: Obesity and CKD pose significant intertwined challenges to global health, affecting a substantial portion of the population worldwide. Obesity is recognized as an independent risk factor, intricately contributing to CKD pathogenesis through mechanisms such as lipotoxicity, chronic inflammation, and insulin resistance. Recent evidence highlights additional factors including hemodynamic changes and intestinal dysbiosis that exacerbate kidney dysfunction in obese individuals, leading to histologic alterations known as obesity-related glomerulopathy (ORG). This narrative review synthesizes current knowledge on the prevalence, pathophysiology, clinical manifestations, and diagnostic strategies of obesity-related kidney disease. Furthermore, it explores mechanistic insights to delineate current therapeutic approaches, future directions for managing this condition and controversies. By elucidating the multifaceted interactions between obesity and kidney health, this review aims to inform clinical practice and stimulate further research to address this global health epidemic effectively.
RESUMO
Macroglossia is an uncommon condition characterized by chronic, painless and abnormal enlargement of the tongue. A multitude of medical conditions can cause macroglossia. Major endocrine and metabolic disorders associated with macroglossia include genetic, congenital and acquired conditions, such as mucopolysaccharidoses; acquired and congenital hypothyroidism and myxedema; transient neonatal diabetes mellitus; acromegaly and amyloidosis. Macroglossia is often associated (~57-60%) with all types of mucopolysaccharidoses, particularly type I (Hurler syndrome) and type II (Hunter syndrome), being a prominent feature of the disorder. It may also occur in patients with acquired and congenital hypothyroidism and myxedema, being a common sign of congenital hypothyroidism with an approximate prevalence of 12-25% at the time of diagnosis. Macroglossia is a predominant oral finding in subjects with transient neonatal diabetes mellitus (~44%), acromegaly (54-69%) and amyloidosis (10-25%), particularly AL amyloidosis (20-40%) whereas is considered a hallmark of the disease. Secondary to macroglossia various disturbances may occur, such as difficulty in speech or eating, orthodontic anomalies or even more serious conditions including upper airway obstruction or obstructive sleep apnea. Until now, no comprehensive review has been conducted focusing on macroglossia in endocrine and metabolic disorders. The objective of this review is to summarize literature on the etiology and epidemiology of macroglossia in major endocrine and metabolic disorders. It highlights key aspects such as pathophysiology, clinical presentation, diagnostic evaluation, management and prognosis of macroglossia in the context of endocrine and metabolic disorders.
RESUMO
Tetracyclines constitute a unique class of antibiotic agents, widely prescribed for both community and hospital infections due to their broad spectrum of activity. Acting by disrupting protein synthesis through tight binding to the 30S ribosomal subunit, their interference is typically reversible, rendering them bacteriostatic in action. Resistance to tetracyclines has primarily been associated with changes in pump efflux or ribosomal protection mechanisms. To address this challenge, tetracycline molecules have been chemically modified, resulting in the development of third-generation tetracyclines. These novel tetracyclines offer significant advantages in treating infections, whether used alone or in combination therapies, especially in hospital settings. Beyond their conventional antimicrobial properties, research has highlighted their potential non-antibiotic properties, including their impact on immunomodulation and malignancy. This review will focus on third-generation tetracyclines, namely tigecycline, eravacycline, and omadacycline. We will delve into their mechanisms of action and resistance, while also evaluating their pros and cons over time. Additionally, we will explore their therapeutic potential, analyzing their primary indications of prescription, potential future uses, and non-antibiotic features. This review aims to provide valuable insights into the clinical applications of third-generation tetracyclines, thereby enhancing understanding and guiding optimal clinical use.
Assuntos
Antibacterianos , Tetraciclinas , Tigeciclina , Tetraciclinas/uso terapêutico , Tetraciclinas/química , Tetraciclinas/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/uso terapêutico , Tigeciclina/uso terapêutico , Tigeciclina/farmacologia , AnimaisRESUMO
Nonalcoholic fatty liver disease (NAFLD) poses an emerging threat topublic health. Nonalcoholic steatohepatitis (NASH) is reported to be the most rapidly rising cause of hepatocellular carcinoma in the western world. Recently, a new term has been proposed: metabolic dysfunction-associated steatotic liver disease (MASLD). The introduction of this new terminology has sparked a debate about the interchangeability of these terms. The pathogenesis of NAFLD/MASLD is thought to be multifactorial, involving both genetic and environmental factors. Among these factors, alterations in gut microbiota and gut dysbiosis have recently garnered significant attention. In this context, this review will further discuss the gut-liver axis, which refers to the bidirectional interaction between the human gut microbiota and the liver. Additionally, the therapeutic potential of probiotics, particularly next-generation probiotics and genetically engineered bacteria, will be explored. Moreover, the role of prebiotics, synbiotics, postbiotics, and phages as well as fecal microbiota transplantation will be analyzed. Particularly for lean patients with NAFLD/MASLD, who have limited treatment options, approaches that modify the diversity and composition of the gut microbiota may hold promise. However, due to ongoing safety concerns with approaches that modulate gut microbiota, further large-scale studies are necessary to better assess their efficacy and safety in treating NAFLD/MASLD.
RESUMO
Atherosclerotic cardiovascular disease poses a significant global health issue, with dyslipidemia standing out as a major risk factor. In recent decades, lipid-lowering therapies have evolved significantly, with statins emerging as the cornerstone treatment. These interventions play a crucial role in both primary and secondary prevention by effectively reducing cardiovascular risk through lipid profile enhancements. Beyond their primary lipid-lowering effects, extensive research indicates that these therapies exhibit pleiotropic actions, offering additional health benefits. These include anti-inflammatory properties, improvements in vascular health and glucose metabolism, and potential implications in cancer management. While statins and ezetimibe have been extensively studied, newer lipid-lowering agents also demonstrate similar pleiotropic effects, even in the absence of direct cardiovascular benefits. This narrative review explores the diverse pleiotropic properties of lipid-modifying therapies, emphasizing their non-lipid effects that contribute to reducing cardiovascular burden and exploring emerging benefits for non-cardiovascular conditions. Mechanistic insights into these actions are discussed alongside their potential therapeutic implications.
RESUMO
Hypovitaminosis D is highly prevalent in critically ill patients, and it has been suggested to be a risk factor for infections, sepsis and higher mortality. We sought to investigate whether serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) in critically ill patients with new onset sepsis are associated with severity and outcome. We prospectively included 50 consecutive critically ill adult cases with new onset sepsis and 50 healthy controls matched for age and sex. PTH and 25(OH)D were determined in serum via electrochemiluminescence immunoassays at inclusion in the study in all cases and controls, and one week after sepsis onset in cases. Patients had reduced 25(OH)D compared to controls at sepsis onset (7.9 ± 3 vs 24.6 ± 6.7 ng/mL, p < 0.001), whilst PTH was similar (median (range): 34.5 (5.7-218.5) vs 44.2 (14.2-98.1) pg/mL, p = 0.35). In patients, 25(OH)D upon enrollment and one week after did not differ significantly (7.9 ± 3 vs 7 ± 4.3 ng/mL, p = 0.19). All patients presented with hypovitaminosis D (25(OH)D < 20 ng/mL), while 40 patients (80 %) had vitamin D deficiency (25(OH)D < 12 ng/mL) at sepsis onset, including all ten (20 %) nonsurvivors, who died within 28 days from sepsis onset. Patients with sepsis (N = 28) and septic shock (N = 22) as well as survivors (N = 40) and nonsurvivors (N = 10) had similar 25(OH)D at enrollment (p > 0.05). 25(OH)D was positively correlated with ionized calcium (r = 0.46, p < 0.001) and negatively with PTH (p < 0.05), while inflammatory biomarkers or the severity scores exhibited no correlation with 25(OH)D. Patients with septic shock and nonsurvivors had lower PTH than patients with sepsis and survivors respectively (42.2 ± 42.9 vs 73.4 ± 61.9 pg/mL, p = 0.04, and 18.3 ± 10.7 vs 69.9 ± 58.8 pg/mL, p = 0.001, respectively). C-reactive protein was negatively associated with PTH (r = -0.44, p = 0.001). In conclusion, vitamin D deficiency was present in 80 % of critically ill patients at sepsis onset, while nonsurvivors exhibited lower PTH than survivors. Additional, larger and multicenter studies are warranted to elucidate the contribution of vitamin D and PTH to the pathogenesis of sepsis and its outcomes.
RESUMO
Renal vein thrombosis (RVT) is a relatively uncommon condition that is most frequently observed in individuals with nephrotic syndrome. While rare, pyelonephritis (PN) may serve as a predisposing factor for secondary RVT. In such cases, one should consider the possibility of RVT when patients fail to respond to appropriate antibiotic treatment. Typically, these patients require additional anticoagulation therapy for a duration of 3 to 6 months, with a generally favorable prognosis. In this report, we present the case of a 74-year-old female who developed RVT due to Klebsiella pneumoniae PN. Additionally, we reviewed 11 cases of PN complicated by RVT, which were documented in the PubMed database over a span of 40 years, emphasizing key elements in diagnostic and therapeutic approaches. Lastly, we elaborated upon the role of thrombo-inflammation, especially in the context of sepsis.
RESUMO
Autoimmune polyglandular syndrome (APS) is a rare group of immune-mediated disorders, which are typically, but not exclusively, related to the presence of endocrine abnormalities. APS type 2 is the most common subtype of the syndrome, more often observed in adulthood, with a characteristic clinical triad, which includes adrenal insufficiency, autoimmune thyroiditis and diabetes mellitus type 1. Adrenal insufficiency is an essential and necessary clinical manifestation of the syndrome, as it is observed in 100 % of the cases, while it can be accompanied by hyperchloremic metabolic acidosis. Herein, we present a 23 years-old patient with adrenal insufficiency in the context of autoimmune polyglandular syndrome type 2 with coexisting autoimmune thyroiditis and metabolic acidosis with an increased anion gap attributed to prolonged malnutrition. Additionally, we analyze the main clinical features of adrenal insufficiency, which is a central component of autoimmune polyglandular syndrome; highlight characteristics that differentiate the major APS subtypes.
Assuntos
Acidose , Insuficiência Adrenal , Poliendocrinopatias Autoimunes , Humanos , Adulto Jovem , Equilíbrio Ácido-Base , Acidose/etiologia , Insuficiência Adrenal/complicações , Insuficiência Adrenal/diagnóstico , Poliendocrinopatias Autoimunes/complicações , Poliendocrinopatias Autoimunes/diagnóstico , Poliendocrinopatias Autoimunes/sangue , Tireoidite Autoimune/complicações , Tireoidite Autoimune/diagnósticoRESUMO
Non-alcoholic fatty liver disease (NAFLD) is a major public health issue worldwide. It is the most common liver disease in Western countries, andits global prevalence is estimated to be up to 35%. However, its diagnosis may be elusive, because liver biopsy is relatively rarely performed and usually only in advanced stages of the disease. Therefore, several non-invasive scores may be applied to more easily diagnose and monitor NAFLD. In this review, we discuss the various biomarkers and imaging scores that could be useful in diagnosing and managing NAFLD. Despite the fact that general measures, such as abstinence from alcohol and modulation of other cardiovascular disease risk factors, should be applied, the mainstay of prevention and management is weight loss. Bariatric surgery may be suggested as a means to confront NAFLD. In addition, pharmacological treatment with GLP-1 analogues or the GIP agonist tirzepatide may be advisable. In this review, we focus on the utility of GLP-1 analogues and GIP agonists in lowering body weight, their pharmaceutical potential, and their safety profile, as already evidenced inanimal and human studies. We also elaborate on other options, such as the use of vitamin E, probiotics, especially next-generation probiotics, and prebiotics in this context. Finally, we explore future perspectives regarding the administration of GLP-1 analogues, GIP agonists, and probiotics/prebiotics as a means to prevent and combat NAFLD. The newest drugs pegozafermin and resmetiron, which seem to be very promising, arealso discussed.
RESUMO
PURPOSE OF REVIEW: Choline is an essential nutrient for human health and cellular homeostasis as it is necessary for the synthesis of lipid cell membranes, lipoproteins, and the synthesis of the neurotransmitter acetylcholine. The aim of this review is to analyze the beneficial effects of choline and its significance in cellular metabolism and various inflammatory pathways, such as the inflammasome. We will discuss the significance of dietary choline in cardiometabolic disorders, such as non-alcoholic fatty liver disease (NAFLD), cardiovascular disease (CVD), and chronic kidney disease (CKD) as well as in cognitive function and associated neuropsychiatric disorders. RECENT FINDINGS: Choline deficiency has been related to the development of NAFLD and cognitive disability in the offspring as well as in adulthood. In sharp contrast, excess dietary intake of choline mediated via the increased production of trimethylamine by the gut microbiota and increased trimethylamine-N-oxide (TMAO) levels has been related to atherosclerosis in most studies. In this context, CVD and CKD through the accumulation of TMAO, p-Cresyl-sulfate (pCS), and indoxyl-sulfate (IS) in serum may be the result of the interplay between excess dietary choline, the increased production of TMAO by the gut microbiota, and the resulting activation of inflammatory responses and fibrosis. A balanced diet, with no excess nor any deficiency in dietary choline, is of outmost importance regarding the prevention of cardiometabolic disorders as well as cognitive function. Large-scale studies with the use of next-generation probiotics, especially Akkermansia muciniphila and Faecalibacterium prausnitzii, should further examine their therapeutic potential in this context.
Assuntos
Doenças Cardiovasculares , Colina , Dieta , Microbioma Gastrointestinal , Insuficiência Renal Crônica , Humanos , Doenças Cardiovasculares/prevenção & controle , Hepatopatia Gordurosa não Alcoólica , Deficiência de Colina/complicações , Metilaminas/metabolismoRESUMO
Irisin, a novel adipo-myokine with metabolic regulatory functions, exerts anti-inflammatory, antioxidant, and anti-apoptotic actions that may confer protection against sepsis-induced organ injury in experimental studies. Until now, only one human study has explored circulating irisin at sepsis onset. We aimed to examine serum irisin and its kinetics in critically ill patients with sepsis and septic shock with regard to sepsis severity and outcome. We enrolled 102 critically ill patients with sepsis or septic shock within 48 h of diagnosis and 102 age- and gender-matched healthy controls. Irisin was determined in serum upon enrollment in all participants and one week later in patients using an immunoenzymatic method. The outcome of sepsis was recorded 28 days after enrollment. At enrollment, circulating irisin was significantly lower in patients than controls (22.3 ± 6.8 µg/L vs. 28.1 ± 6.7 µg/L, p < 0.001), and increased significantly one week later (22.3 ± 6.8 µg/L vs. 26.6 ± 9.5 µg/L, p < 0.001). Irisin was significantly lower in patients who presented with septic shock than those with sepsis, and in non-survivors than survivors both at enrollment and one week later. However, kinetics of irisin did not differ between the groups (p > 0.05). Patients with higher circulating irisin during the first week of sepsis had a better outcome (p < 0.001). Lower irisin was independently associated with 28-day mortality (sepsis onset: HR 0.44, 95% C.I. 0.26-0.77, p = 0.004 and one week after: HR 0.37, 95% C.I. 0.23-0.58, p < 0.001). Irisin was negatively correlated with severity scores, metabolic, and inflammatory biomarkers. Circulating irisin decreases early in sepsis and is an independent predictor of 28-day mortality. Irisin may be a promising diagnostic and prognostic sepsis biomarker; nevertheless, larger studies are needed to explore its role in sepsis.
Assuntos
Sepse , Choque Séptico , Humanos , Choque Séptico/diagnóstico , Fibronectinas , Miocinas , Prognóstico , Estado Terminal , Sepse/diagnóstico , BiomarcadoresRESUMO
Worldwide, sepsis is a well-recognized cause of death. Acute kidney injury (AKI) may be related to sepsis in up to 70% of AKI cases. Sepsis-associated AKI (SA-AKI) is defined as the presence of AKI according to the Kidney Disease: Improving Global Outcomes criteria in the context of sepsis. SA-AKI is categorized into early, which presents during the first 48 h of sepsis, and late, presenting between 48 h and 7 days of sepsis. SA-AKI is associated with a worse prognosis among patients with sepsis. However, there are different SA-AKI phenotypes as well as different pathophysiological pathways of SA-AKI. The aim of this review is to provide an updated synopsis of the pathogenetic mechanisms underlying the development of SA-AKI as well as to analyze its different phenotypes and prognosis. In addition, potential novel diagnostic and prognostic biomarkers as well as therapeutic approaches are discussed. A plethora of mechanisms are implicated in the pathogenesis of SA-AKI, including inflammation and metabolic reprogramming during sepsis; various types of cell death such as apoptosis, necroptosis, pyroptosis and ferroptosis; autophagy and efferocytosis; and hemodynamic changes (macrovascular and microvascular dysfunction). Apart from urine output and serum creatinine levels, which have been incorporated in the definition of AKI, several serum and urinary diagnostic and prognostic biomarkers have also been developed, comprising, among others, interleukins 6, 8 and 18, osteoprotegerin, galectin-3, presepsin, cystatin C, NGAL, proenkephalin A, CCL-14, TIMP-2 and L-FABP as well as biomarkers stemming from multi-omics technologies and machine learning algorithms. Interestingly, the presence of long non-coding RNAs (lncRNAs) as well as microRNAs (miRNAs), such as PlncRNA-1, miR-22-3p, miR-526b, LncRNA NKILA, miR-140-5p and miR-214, which are implicated in the pathogenesis of SA-AKI, may also serve as potential therapeutic targets. The combination of omics technologies represents an innovative holistic approach toward providing a more integrated view of the molecular and physiological events underlying SA-AKI as well as for deciphering unique and specific phenotypes. Although more evidence is still necessary, it is expected that the incorporation of integrative omics may be useful not only for the early diagnosis and risk prognosis of SA-AKI, but also for the development of potential therapeutic targets that could revolutionize the management of SA-AKI in a personalized manner.
Assuntos
Injúria Renal Aguda , MicroRNAs , Sepse , Humanos , Sepse/diagnóstico , Prognóstico , Biomarcadores , Fragmentos de Peptídeos , Receptores de LipopolissacarídeosRESUMO
Lipoprotein(a) [Lp(a)] consists of a low-density lipoprotein-like molecule and an apolipoprotein(a) [apo(a)] particle. Lp(a) has been suggested to be an independent risk factor of atherosclerotic cardiovascular disease (ASCVD). Lp(a) plasma levels are considered to be 70-90% genetically determined through the codominant expression of the LPA gene. Therefore, Lp(a) levels are almost stable during an individual's lifetime. This lifelong stability, together with the difficulties in measuring Lp(a) levels in a standardized manner, may account for the scarcity of available drugs targeting Lp(a). In this review, we synopsize the latest data regarding the structure, metabolism, and factors affecting circulating levels of Lp(a), as well as the laboratory determination measurement of Lp(a), its role in the pathogenesis of ASCVD and thrombosis, and the potential use of various therapeutic agents targeting Lp(a). In particular, we discuss novel agents, such as antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) that are currently being developed and target Lp(a). The promising role of muvalaplin, an oral inhibitor of Lp(a) formation, is then further analyzed.
Assuntos
Aterosclerose , Doenças Cardiovasculares , Humanos , Lipoproteína(a)/genética , Aterosclerose/tratamento farmacológico , Fatores de Risco , Apoproteína(a) , Apolipoproteínas ARESUMO
ApoB is the main protein of triglyceride-rich lipoproteins and is further divided into ApoB48 in the intestine and ApoB100 in the liver. Very low-density lipoprotein (VLDL) is produced by the liver, contains ApoB100, and is metabolized into its remnants, intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL). ApoB100 has been suggested to play a crucial role in the formation of the atherogenic plaque. Apart from being a biomarker of atherosclerosis, ApoB100 seems to be implicated in the inflammatory process of atherosclerosis per se. In this review, we will focus on the structure, the metabolism, and the function of ApoB100, as well as its role as a predictor biomarker of cardiovascular risk. Moreover, we will elaborate upon the molecular mechanisms regarding the pathophysiology of atherosclerosis, and we will discuss the disorders associated with the APOB gene mutations, and the potential role of various drugs as therapeutic targets.
RESUMO
Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area.
Assuntos
Compostos Benzidrílicos , Disruptores Endócrinos , Fenóis , Ácidos Ftálicos , Animais , Feminino , Gravidez , Disruptores Endócrinos/toxicidade , Obesidade/induzido quimicamente , Aumento de Peso , HumanosRESUMO
Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal type of pneumonitis, which may have devastating consequences. Typically, it occurs in immunocompromised patients, with the natural history varying depending on the presence or not of HIV infection. Staining and polymerase chain reaction (PCR) testing in induced sputum or bronchoalveolar lavage (BAL) is the cornerstone of the diagnosis, while trimethoprim-sulfamethoxazole is the treatment of choice. The etiological association of biologic agents with the occurrence of PJP is not entirely clear. Adalimumab is a fully human monoclonal anti-TNF-alpha antibody, which has been introduced relatively recently in the treatment of autoimmune inflammatory diseases, such as rheumatoid arthritis. In contrast to other biologic agents, such as Alemtuzumab or Infliximab, there are a small number of reports that support the drug's ability to trigger the occurrence of PJP. Hereby, we present a 53-year-old female patient with a medical history of rheumatoid arthritis on Adalimumab therapy, who developed PJP and we will discuss the main characteristics of PJP and the possible contribution of biologics to the occurrence of the infection.
Assuntos
Artrite Reumatoide , Infecções por HIV , Pneumocystis carinii , Pneumonia por Pneumocystis , Feminino , Humanos , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/tratamento farmacológico , Adalimumab/efeitos adversos , Inibidores do Fator de Necrose Tumoral , Artrite Reumatoide/tratamento farmacológicoRESUMO
PURPOSE OF REVIEW: To examine the epidemiological data on obesity and leukemia; evaluate the effect of obesity on leukemia outcomes in childhood acute lymphoblastic leukemia (ALL) survivors; assess the potential mechanisms through which obesity may increase the risk of leukemia; and provide the effects of obesity management on leukemia. Preventive (diet, physical exercise, obesity pharmacotherapy, bariatric surgery) measures, repurposing drugs, candidate therapeutic agents targeting oncogenic pathways of obesity and insulin resistance in leukemia as well as challenges of the COVID-19 pandemic are also discussed. RECENT FINDINGS: Obesity has been implicated in the development of 13 cancers, such as breast, endometrial, colon, renal, esophageal cancers, and multiple myeloma. Leukemia is estimated to account for approximately 2.5% and 3.1% of all new cancer incidence and mortality, respectively, while it represents the most frequent cancer in children younger than 5 years. Current evidence indicates that obesity may have an impact on the risk of leukemia. Increased birthweight may be associated with the development of childhood leukemia. Obesity is also associated with worse outcomes and increased mortality in leukemic patients. However, there are several limitations and challenges in meta-analyses and epidemiological studies. In addition, weight gain may occur in a substantial number of childhood ALL survivors while the majority of studies have documented an increased risk of relapse and mortality among patients with childhood ALL and obesity. The main pathophysiological pathways linking obesity to leukemia include bone marrow adipose tissue; hormones such as insulin and the insulin-like growth factor system as well as sex hormones; pro-inflammatory cytokines, such as IL-6 and TNF-α; adipocytokines, such as adiponectin, leptin, resistin, and visfatin; dyslipidemia and lipid signaling; chronic low-grade inflammation and oxidative stress; and other emerging mechanisms. Obesity represents a risk factor for leukemia, being among the only known risk factors that could be prevented or modified through weight loss, healthy diet, and physical exercise. Pharmacological interventions, repurposing drugs used for cardiometabolic comorbidities, and bariatric surgery may be recommended for leukemia and obesity-related cancer prevention.
Assuntos
Pandemias , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Obesidade/complicações , Obesidade/epidemiologia , Leptina , Fatores de Risco , Adipocinas , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaçõesRESUMO
PURPOSE OF REVIEW: The role of the gut microbiota in modulating blood pressure is increasingly being recognized, currently. The purpose of this review is to summarize recent findings about the mechanisms involved in hypertension with regard to the phenomenon of "gut dysbiosis." RECENT FINDINGS: Gut dysbiosis, i.e., the imbalance between the gut microbiota and the host, is characterized by a disruption of the tight junction proteins, such as occludins, claudins, and JAMs (junctional adhesion molecules), resulting in increased gut permeability or the so called "leaky gut." Due to the influence of genetic as well as environmental factors, various metabolites produced by the gut microbiota, such as indole and p-cresol, are increased. Thereby, uremic toxins, such as indoxyl sulfates and p-cresol sulfates, accumulate in the blood and the urine, causing damage in the podocytes and the tubular cells. In addition, immunological mechanisms are implicated as well. In particular, a switch from M2 macrophages to M1 macrophages, which produce pro-inflammatory cytokines, occurs. Moreover, a higher level of Th17 cells, releasing large amounts of interleukin-17 (IL-17), has been reported, when a diet rich in salt is consumed. Therefore, apart from the aggravation of uremic toxins, which may account for direct harmful effects on the kidney, there is inflammation not only in the gut, but in the kidneys as well. This crosstalk between the gut and the kidney is suggested to play a crucial role in hypertension. Notably, the brain is also implicated, with an increasing sympathetic output. The brain-gut-kidney axis seems to be deeply involved in the development of hypertension and chronic kidney disease (CKD). The notion that, by modulating the gut microbiota, we could regulate blood pressure is strongly supported by the current evidence. A healthy diet, low in animal protein and fat, and low in salt, together with the utilization of probiotics, prebiotics, synbiotics, or postbiotics, may contribute to our fight against hypertension.
RESUMO
Long COVID (LC) encompasses a constellation of long-term symptoms experienced by at least 10% of people after the initial SARS-CoV-2 infection, and so far it has affected about 65 million people. The etiology of LC remains unclear; however, many pathophysiological pathways may be involved, including viral persistence; a chronic, low-grade inflammatory response; immune dysregulation and a defective immune response; the reactivation of latent viruses; autoimmunity; persistent endothelial dysfunction and coagulopathy; gut dysbiosis; hormonal and metabolic dysregulation; mitochondrial dysfunction; and autonomic nervous system dysfunction. There are no specific tests for the diagnosis of LC, and clinical features including laboratory findings and biomarkers may not specifically relate to LC. Therefore, it is of paramount importance to develop and validate biomarkers that can be employed for the prediction, diagnosis and prognosis of LC and its therapeutic response, although this effort may be hampered by challenges pertaining to the non-specific nature of the majority of clinical manifestations in the LC spectrum, small sample sizes of relevant studies and other methodological issues. Promising candidate biomarkers that are found in some patients are markers of systemic inflammation, including acute phase proteins, cytokines and chemokines; biomarkers reflecting SARS-CoV-2 persistence, the reactivation of herpesviruses and immune dysregulation; biomarkers of endotheliopathy, coagulation and fibrinolysis; microbiota alterations; diverse proteins and metabolites; hormonal and metabolic biomarkers; and cerebrospinal fluid biomarkers. At present, there are only two reviews summarizing relevant biomarkers; however, they do not cover the entire umbrella of current biomarkers, their link to etiopathogenetic mechanisms or the diagnostic work-up in a comprehensive manner. Herein, we aim to appraise and synopsize the available evidence on the typical laboratory manifestations and candidate biomarkers of LC, their classification based on pathogenetic mechanisms and the main LC symptomatology in the frame of the epidemiological and clinical aspects of the syndrome and furthermore assess limitations and challenges as well as potential implications in candidate therapeutic interventions.
Assuntos
COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Proteínas de Fase Aguda , Biomarcadores , InflamaçãoRESUMO
The nucleotide-binding domain-like receptor protein 3 (NLRP3) inflammasome in the kidney and the heart is increasingly being suggested to play a key role in mediating inflammation. In the kidney, NLRP3 activation was associated with the progression of diabetic kidney disease. In the heart, activation of the NLRP3 inflammasome was related to the enhanced release of interleukin-1ß (IL-1ß) and the subsequent induction of atherosclerosis and heart failure. Apart from their glucose-lowering effects, SGLT-2 inhibitors were documented to attenuate activation of the NLRP3, thus resulting in the constellation of an anti-inflammatory milieu. In this review, we focus on the interplay between SGLT-2 inhibitors and the inflammasome in the kidney, the heart and the neurons in the context of diabetes mellitus and its complications.