Biomimetic nanoplatform with microbiome modulation and antioxidant functions ameliorating insulin resistance and pancreatic ß-cell dysfunction for T2DM management.

Insulin resistance and pancreatic ß-cell dysfunction are the main pathogenesis of type 2 diabetes mellitus (T2DM). However, insulin therapy and diabetes medications do not effectively solve the two problems simultaneously. In this study, a biomimetic oral hydrogen nanogenerator that leverages the benefits of edible plant-derived exosomes and hydrogen therapy was constructed to overcome this dilemma by modulating gut microbiota and ameliorating oxidative stress and inflammatory responses. Hollow mesoporous silica (HMS) nanoparticles encapsulating ammonia borane (A) were used to overcome the inefficiency of H2 delivery in traditional hydrogen therapy, and exosomes originating from ginger (GE) were employed to enhance biocompatibility and regulate intestinal flora. Our study showed that HMS/A@GE not only considerably ameliorated insulin resistance and liver steatosis, but inhibited the dedifferentiation of islet ß-cell and enhanced pancreatic ß-cell proportion in T2DM model mice. In addition to its antioxidant and anti-inflammatory effects, HMS/A@GE augmented the abundance of Lactobacilli spp. and tryptophan metabolites, such as indole and indole acetic acid, which further activated the AhR/IL-22 pathway to improve intestinal-barrier function and metabolic impairments. This study offers a potentially viable strategy for addressing the current limitations of diabetes treatment by integrating gut-microbiota remodelling with antioxidant therapies.

A novel glycopeptide from mountain-cultivated ginseng residue protects type 2 diabetic symptoms-induced heart failure.

ETHNOPHARMACOLOGICAL RELEVANCE: Mountain-cultivated Panax ginseng C.A.Mey. (MCG) with high market price and various properties was valuable special local product in Northeast of Asia. MCG has been historically used to mitigate heart failure (HF) for thousand years, HF is a clinical manifestation of deficiency of "heart-qi" in traditional Chinese medicine. However, there was little report focus on the activities of extracted residue of MCG. AIM OF THE STUDY: A novel glycopeptide (APMCG-1) was isolated from step ethanol precipitations of alkaline protease-assisted extract from MCG residue. MATERIALS AND METHODS: The molecular weight and subunit structure of APMCG-1 were determined by FT-IR, HPLC and GPC technologies, as well as the H9c2 cells, Tg (kdrl:EGFP) zebrafish were performed to evaluated the protective effect of APMCG-1. RESULTS: APMCG-1 was identified as a glycopeptide containing seven monosaccharides and seven amino acids via O-lined bonds. Further, in vitro, APMCG-1 significantly decreased reactive oxygen species production and lactate dehydrogenase contents in palmitic acid (PA)-induced H9c2 cells. APMCG-1 also attenuated endoplasmic reticulum stress and mitochondria-mediated apoptosis in H9c2 cells via the PI3K/AKT signaling pathway. More importantly, APMCG-1 reduced the blood glucose, lipid contents, the levels of heart injury, oxidative stress and inflammation of 5 days post fertilization Tg (kdrl:EGFP) zebrafish with type 2 diabetic symptoms in vivo. CONCLUSIONS: APMCG-1 protects PA-induced H9c2 cells while reducing cardiac dysfunction in zebrafish with type 2 diabetic symptoms. The present study provides a new insight into the development of natural glycopeptides as heart-related drug therapies.

Assessing the potential fasting and postprandial mechanisms involved in the acute hypoglycemic and anti-hyperglycemic effects of four selected plants from Iran used in traditional Persian medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Syzygium cumini (L.) skeels mitigate diabetic nephropathy by regulating Nrf2 pathway and mitocyhondrial dysfunction: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.

Emerging role of PES1 in disease: A promising therapeutic target?

Pescadillo ribosomal biogenesis factor 1 (PES1), a nucleolar protein initially identified in zebrafish, plays an important role in embryonic development and ribosomal biogenesis. Notably, PES1 has been found to be overexpressed in a number of cancer types, where it contributes to tumorigenesis and cancer progression by promoting cell proliferation, suppressing cellular senescence, modulating the tumor microenvironment (TME) and promoting drug resistance in cancer cells. Moreover, recent emerging evidence suggests that PES1 expression is significantly elevated in the livers of Type 2 diabetes mellitus (T2DM) and obese patients, indicating its involvement in the pathogenesis of metabolic diseases through lipid metabolism regulation. In this review, we present the structural characteristics and biological functions of PES1, as well as complexes in which PES1 participates. Furthermore, we comprehensively summarize the multifaceted role of PES1 in various diseases and the latest insights into its underlying molecular mechanisms. Finally, we discuss the potential clinical translational perspectives of targeting PES1, highlighting its promising as a therapeutic intervention and treatment target.

Context-dependent role of sirtuin 2 in inflammation.

Sirtuin 2 is a member of the sirtuin family nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, known for its regulatory role in different processes, including inflammation. In this context, sirtuin 2 has been involved in the modulation of key inflammatory signaling pathways and transcription factors by deacetylating specific targets, such as nuclear factor κB and nucleotide-binding oligomerization domain-leucine-rich-repeat and pyrin domain-containing protein 3 (NLRP3). However, whether sirtuin 2-mediated pathways induce a pro- or an anti-inflammatory response remains controversial. Sirtuin 2 has been implicated in promoting inflammation in conditions such as asthma and neurodegenerative diseases, suggesting that its inhibition in these conditions could be a potential therapeutic strategy. Conversely, arthritis and type 2 diabetes mellitus studies suggest that sirtuin 2 is essential at the peripheral level and, thus, its inhibition in these pathologies would not be recommended. Overall, the precise role of sirtuin 2 in inflammation appears to be context-dependent, and further investigation is needed to determine the specific molecular mechanisms and downstream targets through which sirtuin 2 influences inflammatory processes in various tissues and pathological conditions. The present review explores the involvement of sirtuin 2 in the inflammation associated with different pathologies to elucidate whether its pharmacological modulation could serve as an effective strategy for treating this prevalent symptom across various diseases.

The association of isocarbophos and isofenphos with different types of glucose metabolism: The role of inflammatory cells.

To investigate the associations between isocarbophos and isofenphos with impaired fasting glucose (IFG) and type 2 diabetes mellitus (T2DM), and to assess the mediation roles of inflammation cells. There were 2701 participants in the case-control study, including 896 patients with T2DM, 900 patients with IFG, 905 subjects with NGT. Plasma isocarbophos and isofenphos concentrations were measured using gas chromatography and triple quadrupole tandem mass spectrometry. Generalized linear models were used to calculate the relationships between plasma isofenphos and isocarbophos levels with inflammatory factor levels and T2DM. Inflammatory cell was used as mediators to estimate the mediating effects on the above associations. Isocarbophos and isofenphos were positively related with T2DM after adjusting for other factors. The odds ratio (95% confidence interval) (OR (95%CI)) for T2DM was 1.041 (1.015, 1.068) and for IFG was 1.066 (1.009, 1.127) per unit rise in ln-isocarbophos. The prevalence of T2DM increased by 6.4% for every 1 unit more of ln-isofenphos (OR (95% CI): 1.064 (1.041, 1.087)). Additionally, a 100% rise in ln-isocarbophos was linked to 3.3% higher ln-HOMA2IR and a 0.029 mmol/L higher glycosylated hemoglobin (HbA1c) (95% CI: 0.007, 0.051). While a 100% rise in ln-isofenphos was linked to increase in ln-HOMA2 and ln-HOMA2IR of 5.8% and 3.4%, respectively. Furthermore, white blood cell (WBC) and neutrophilic (NE) were found to be mediators in the relationship between isocarbophos and T2DM, and the corresponding proportions were 17.12% and 17.67%, respectively. Isofenphos and isocarbophos are associated with IFG and T2DM in the rural Chinese population, WBC and NE have a significant role in this relationship.

Estudiar y trabajar como factores de riesgo en estudiantes de enfermería, Universidad Nacional Formosa, 2022 / Study and work as risk factors in nursing students, National University of Formosa,2022

Objetivo: Correlacionar la variable principal sostén del hogar con las variables género, edad, horas de trabajo, horas de sueño y factores de riesgo cardiovascular (índice de masa corporal, hipertensión arterial, dislipemia y diabetes mellitus), en estudiantes de 3º, 4 y 5º año de la Licenciatura en Enfermería, Universidad Nacional de Formosa. Metodología: estudio descriptivo, correlacional, transversal realizado en 214 estudiantes, durante el año 2022, utilizándose un cuestionario on-line autoadministrado, estructurado y medición de peso y talla. Resultados: el 76% fueron mujeres; 64%, principal fueron principal sostén del hogar, 57% refirió dormir menos de 6 horas al día, 15 % trabaja más de 41 horas semanales; 67% tuvo respuestas no saludables a la variable estrés, para la variable actividad física este valor ascendió a 71% y el 53,8% presentó exceso de peso. Se encontró asociación significativa entre ser el principal sostén del hogar con exceso de peso, trabajar 41 horas o más semanalmente, dormir menos de 6 horas al día y con la presencia de 3 o más factores de riesgo cardiovascular. Conclusiones: Las condiciones de vida que afrontan los estudiantes que de manera simultánea estudian, trabajan y son principal sostén del hogar pueden generar estrés, el cual es un factor de riesgo para las enfermedades cardiovasculares[AU]

Objetive: to correlate the main variable of primary income earner or primary breadwinner with gender, age, working hours, sleep hours, and cardiovascular disease risk factors (body mass index, hypertension, dyslipidemia, and diabetes mellitus) in 3rd, 4th, and 5th-year nursing students at the Nursing Program at the National University of Formosa. Methodology: The study was a descriptive, correlational, cross-sectional, conducted with 214 students during 2022 using a self-administered structured online questionnaire and measurement of weight and height. Results: 76% were women, 64% were the main breadwinner, 57% reported sleeping less than 6 hours a day, 15% working more than 41 hours per week; 67% had unhealthy responses to the stress variable, this value rose to 71% for the physical activity variable, and 53.8% were overweight. A significant association was found between the main variable of primary breadwinner and being overweight, working 41 or more hours weekly, and the presence of 3 or more cardiovascular risk factors. Conclusions: The living conditions faced by students who simultaneously study and work, and being the main breadwinner in the household can generate stress, which is a risk factor for cardiovascular diseases[AU]

Objetivo:: correlacionar a variável principal de sustento econômico do lar com as variáveis gênero, idade, horas de trabalho, horas de sono e fatores de risco cardiovascular (índice de massa corporal,hipertensão arterial, dislipidemia e diabetes mellitus) em estudantes do 3º, 4º e 5º ano do curso de graduação em Enfermagem, Universidade Nacional de Formosa. Metodologia: O estudo foi descritivo, correlacional e transversal, realizado em 214 estudantes durante o ano de 2022. Foi utilizado um questionário online autoadministrado e estruturado, e a medição de peso e altura dos estudantes foi realizada. Resultados: 76% dos estudantes eram mulheres; 64% eram o principal sustento econômico do lar; 57% relataram dormir menos de 6 horas por dia, 15% responderam que trabalham mais de 41 horas por semana; em relação aos fatores de risco cardiovascular, 67% tiveram respostas não saudáveis para a variável estresse, para a variável atividade física esse valor aumentou para 71% e 53,8% apresentaram excesso de peso. Foi encontrada uma associação significativa entre a variável principal de sustento econômico do lar com as variáveis excesso de peso, trabalhar 41 horas ou mais por semana, dormir menos de 6 horas al día e a presença de 3 ou mais fatores de risco cardiovascular. Conclusões: As condições de vida enfrentadas pelos estudantes que simultaneamente estudam, trabalham e são o principal sustento do lar podem gerar estresse, que é um fator de risco para doenças cardiovasculares[AU]

Prevalência de Influenza A, vírus sincicial respiratório eSARS-CoV-2 em pacientes com síndrome respiratóriaaguda grave em Passo Fundo, Rio Grande do Sul / Prevalence of Influenza A, respiratory syncytial virus andSARS-CoV-2 in patients with severe acute respiratorysyndrome in Passo Fundo, Rio Grande do Sul

A síndrome respiratória aguda grave (SRAG) é caracterizada por sintomas de febre alta, tosse e dispneia, e, na maioria dos casos, relacionada a uma quantidade reduzida de agentes infecciosos. O objetivo foi avaliar a prevalência dos vírus respiratórios Influenza A (FluA), vírus sincicial respiratório (RSV) e do novo coronavírus (SARS-CoV-2) em pacientes com internação hospitalar por SRAG. Estudo transversal, com pacientes em internação hospitalar com SRAG entre novembro de 2021 e maio de 2022. Dados sociodemográficos e clínicos e amostras da nasofaringe foram coletados/as, as quais foram submetidas à extração de RNA e testadas quanto à positividade para Influenza A, RSV e SARS-CoV-2 por meio da técnica de PCR em tempo real pelo método SYBR Green. Foram incluídos 42 pacientes, sendo 59,5% do sexo feminino, 57,1% idosos, 54,8% com ensino fundamental. A maior parte dos pacientes reportou hábito tabagista prévio ou atual (54,8%), não etilista (73,8%) e 83,3% deles apresentavam alguma comorbidade, sendo hipertensão arterial sistêmica e diabetes mellitus tipo 2 as mais prevalentes. Um total de 10,5% dos pacientes testou positivo para FluA, nenhuma amostra positiva para RSV e 76,3% positivos para SARS-CoV-2. Na população estudada, SRAG com agravo hospitalar foi observado em maior proporção, em mulheres, idosos e pessoas com comorbidades, embora sem significância estatística, sendo o novo coronavírus o agente etiológico mais relacionado, o que evidencia a patogenicidade desse agente e suas consequências ainda são evidentes após quase 2 anos de período pandêmico.

Severe acute respiratory syndrome (SARS) is characterized by symptoms of high fever, cough and dyspnea, and is in most cases related to a reduced amount of infectious agents. The objective was to assess the prevalence of respiratory viruses Influenza A (FluA), respiratory syncytial virus (RSV) and the new coronavirus (SARS-CoV-2) in patients hospitalized for SARS. Cross-sectional study, with patients hospitalized with SARS between November 2021 and May 2022. Sociodemographic and clinical data and nasopharyngeal samples were collected, which were subjected to RNA extraction and tested for positivity for Influenza A, RSV and SARS-CoV-2 using the real-time PCR technique using the SYBR Green method. 42 patients were included, 59.5% female, 57.1% elderly, 54.8% with primary education. Most patients reported previous or current smoking habits (54.8%), non-drinkers (73.8) and 83.3% of them had some comorbidity, with systemic arterial hypertension and type 2 diabetes mellitus being the most prevalent. A total of 10.5% of patients tested positive for FluA, no samples positive for RSV, and 76.3% positive for SARS-CoV-2. In the studied population, SARS with hospital injury was observed more frequently in women and the elderly, with associated comorbidities, with the new coronavirus being the most related etiological agent, which shows, although not statistically significant, that the pathogenicity of this agent and its consequences are still evident after almost 2 years of period pandemic.

Rastreamento da síndrome metabólica em participantesdo programa Universidade Aberta da Terceira Idade / Metabolic syndrome screening in the participantsat the Open University of the Third Age

Hábitos alimentares inadequados, sedentarismo e a maior expectativa de vida da população contribuem significativamente para a prevalência da síndrome metabólica. Essa doença predispõe uma pessoa a desenvolver diabetes mellitus tipo 2 e doenças cardiovasculares, as quais têm um amplo impacto na saúde pública, induzindo sobrecarga no sistema de saúde e reduzindo a qualidade de vida dos indivíduos afetados. A síndrome metabólica é uma doença multifatorial e está relacionada ao processo de envelhecimento, contudo, ainda há uma lacuna significativa, em termos de estudos, sobre a prevalência da condição em populações idosas. Nesse contexto, o presente estudo objetivou rastrear a prevalência da síndrome metabólica em participantes da Universidade Aberta da Terceira Idade (UNATI), localizada em Francisco Beltrão, Paraná. Os critérios diagnósticos de síndrome metabólica abordados nesta pesquisa incluem: circunferência abdominal ≥ 90 cm para homens e ≥ 80 cm para mulheres, triglicerídeos ≥ 150 mg/dL, HDL ≤ 40 mg/dL para homens e ≤ 50 mg/dL para mulheres, pressão arterial sistólica ≥ 130 mmHg e/ou pressão arterial diastólica ≥ 85 mmHg ou estar em farmacoterapia para hipertensão, além de glicemia de jejum ≥ 100 mg/dL ou estar em tratamento farmacológico para diabetes. Um total de 44 idosos foram avaliados, apresentando uma média de idade de 66,9 ± 7,1 anos, com uma predominância de mulheres (88%). Os resultados revelaram uma prevalência alarmante de síndrome metabólica, atingindo 36,4% da amostra estudada. Além disso, observou-se uma alta prevalência de condições associadas, como hipertensão arterial (67,2%), sobrepeso (58,6%) e obesidade visceral (31%). Esses achados ressaltam a importância da implementação de medidas preventivas direcionadas à promoção da qualidade de vida saudável e ao controle dos fatores de risco metabólicos.

Inadequate dietary habits, sedentary lifestyle, and increased life expectancy significantly contribute to the prevalence of metabolic syndrome. This condition predisposes an individual to develop type 2 diabetes mellitus and cardiovascular diseases, which have a broad impact on public health, inducing a burden on the healthcare system and reducing the quality of life of affected individuals. Metabolic syndrome is a multifactorial disease and is related to the aging process; however, there is still a significant gap in terms of studies on the prevalence of the condition in elderly populations. In this context, this study aimed to screen the prevalence of metabolic syndrome in participants of the Open University for the Third Age (UNATI), located in Francisco Beltrão, Paraná. The diagnostic criteria for metabolic syndrome addressed in this research include: abdominal circumference ≥ 90 cm for men and ≥ 80 cm for women, triglycerides ≥ 150 mg/dL, HDL ≤ 40 mg/dL for men and ≤ 50 mg/dL for women, systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 85 mmHg or being on pharmacotherapy for hypertension, in addition to fasting glucose ≥ 100 mg/dL or being on pharmacological treatment for diabetes. A total of 44 elderly individuals were evaluated, with a mean age of 66.9 ± 7.1 years, predominantly women (88%). The results revealed an alarming prevalence of metabolic syndrome, affecting 36.4% of the studied sample. Furthermore, a high prevalence of associated conditions was observed, such as arterial hypertension (67.2%), overweight (58.6%), and visceral obesity (31%). These findings underscore the importance of implementing preventive measures aimed at promoting healthy lifestyles and controlling metabolic risk factors.

Investigating the interplay between mitophagy and diabetic neuropathy: Uncovering the hidden secrets of the disease pathology.

Mitophagy, the cellular process of selectively eliminating damaged mitochondria, plays a crucial role in maintaining metabolic balance and preventing insulin resistance, both key factors in type 2 diabetes mellitus (T2DM) development. When mitophagy malfunctions in diabetic neuropathy, it triggers a cascade of metabolic disruptions, including reduced energy production, increased oxidative stress, and cell death, ultimately leading to various complications. Thus, targeting mitophagy to enhance the process may have emerged as a promising therapeutic strategy for T2DM and its complications. Notably, plant-derived compounds with ß-cell protective and mitophagy-stimulating properties offer potential as novel therapeutic agents. This review highlights the intricate mechanisms linking mitophagy dysfunction to T2DM and its complications, particularly neuropathy, elucidating potential therapeutic interventions for this debilitating disease.

Association Between Diabetes Mellitus and Postoperative Opioid use: A Meta-Analysis.

INTRODUCTION: Diabetes mellitus (DM) is a prevalent metabolic disorder associated with various postoperative complications. The association between DM and postoperative opioid use remains unclear, with conflicting evidence in the literature. This systematic review and meta-analysis comprehensively evaluated the association between DM and postoperative opioid consumption, pain sensation, and adverse effects in surgical patients. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic search of electronic databases identified studies investigating the relationship between DM and postoperative pain outcomes. Eligible studies, both prospective and retrospective, were included based on the predefined criteria. Data extraction and quality assessment were performed independently by the authors. Meta-analyses were performed using Review Manager 5. RESULTS: Among 100 initially identified articles, five studies met the inclusion criteria. In the meta-analysis, 473 participants were included. The results indicated that patients with DM had significantly higher postoperative opioid consumption (standardized mean difference, 0.79; 95% confidence interval, 0.26-1.31; P = 0.003) than those in the control group, with substantial heterogeneity (I2 = 83%). No significant differences in postoperative pain scale scores at rest or during movement were observed. Adverse effects, including nausea, vomiting, and pruritus, showed varied outcomes, whereas overall satisfaction did not differ between the two groups. CONCLUSIONS: This meta-analysis provides evidence that patients with DM undergoing surgery consume more opioids postoperatively. Understanding the association between DM and pain management is crucial for optimizing perioperative care in this patient population.

Bile duct injury following laparoscopic cholecystectomy in a patient with a trifurcated hepatic duct: A case report.

INTRODUCTION AND IMPORTANCE: Iatrogenic bile duct injury is a serious complication of laparoscopic cholecystectomy, often due to misinterpretation of biliary tree anatomy. Anatomical variations, patient condition, gallbladder pathology, and surgeon-related factors are key risk factors for bile duct injury. CASE PRESENTATION: A 68-year-old male with a history of hypertension and type 2 diabetes mellitus underwent Laparoscopic cholecystectomy for symptomatic gallstones. One-month post-surgery, he developed right upper quadrant pain, jaundice, and elevated liver enzymes. Magnetic resonance cholangiopancreatography (MRCP) showed a hilar confluence stricture affecting the right posterior and left hepatic ducts, with mild-to-moderate dilation of upstream intrahepatic bile ducts. CLINICAL DISCUSSION: Trifurcation of the hepatic duct is a rare but clinically significant anatomical variation that can predispose patients to common bile duct injuries. Preoperative MRCP can identify such variations, aiding in surgical planning. However, intraoperative recognition and management of these anatomical differences are crucial to prevent bile duct injuries. This is particularly important in low-resource settings where routine preoperative imaging may not be feasible. CONCLUSION: Accurate intraoperative identification of biliary tree anatomical variations is essential to prevent iatrogenic injuries during surgery. Preoperative imaging, when available, can provide valuable information to assist in surgical planning. Additionally, the use of intra-operative cholangiogram (IOC) should be considered to help identify and manage anatomical variations, thereby reducing the risk of bile duct injuries.

Schisandra chinensis lignans improve insulin resistance by targeting TLR4 and activating IRS-1/PI3K/AKT and NF-κB signaling pathways.

Schisandra chinensis, a traditional Chinese medicine, has been widely applied in China to treat diabetes and its complications. The aim of this study was to discover the active compounds and explain related molecular mechanism contributing to the anti-diabetic effect of Schisandra chinensis. Herein, the therapeutic effects of Schisandra chinensis extracts on type 2 diabetes mellitus (T2DM) were firstly confirmed in vivo. Subsequently, various lignans were isolated from Schisandra chinensis and tested for hypoglycemic activity in palmitic acid-induced insulin-resistant HepG2 (IR-HepG2) cells. Among these lignans, R-biar-(7S,8R)-6,7,8,9-tetrahydro-1,2,3,12,13,14-hexamethoxy-7,8-dimethyl-7-dibenzo [a, c] cyclooctenol (compound 2) and Gomisin A (compound 4) were identified significantly increased the glucose consumption in IR-HepG2 cells. Meanwhile, compounds 2 and 4 activated the insulin receptor substrate-1 (IRS-1)/phosphoinositide 3-kinase (PI3K)/Ak strain transforming (AKT) pathway, which regulates glucose transporter 2 (GLUT2) and glucose-6-phosphatase (G6Pase), essential for gluconeogenesis and glucose uptake. These compounds also inhibited the nuclear factor-κB (NF-κB) signaling pathway, reducing interleukin-6 (IL-6) levels. Importantly, the hypoglycemic effects of compounds 2 and 4 were diminished after Toll-like receptor 4 (TLR4) knockdown. Cellular thermal shift assays confirmed increased TLR4 protein stability upon treatment with these compounds, indicating direct binding to TLR4. Furthermore, TLR4 knockdown reversed the effects of compounds 2 and 4 on the NF-κB and IRS-1/PI3K/AKT pathways. Taken together, compounds 2 and 4 alleviate IR by targeting TLR4, thereby modulating the NF-κB and IRS-1/PI3K/AKT pathways. These findings suggest that compounds 2 and 4 could be developed as therapeutic agents for T2DM.

Associations of dinitroaniline herbicide exposure, genetic susceptibility, and lifestyle with glucose dysregulation: A gene-environment interaction study from the Wuhan-Zhuhai cohort.

OBJECTIVE: To assess the association of dinitroaniline herbicides as well as their interactions with genetic susceptibility and lifestyle with glucose dysregulation. METHODS: A total of 4310 Chinese urban adults from the baseline of the Wuhan-Zhuhai Cohort were included in the cross-sectional study. A follow-up panel from the cohort was included in the longitudinal study, including 158 participants with 432 observations. Glucose dysregulation, including fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), type 2 diabetes mellitus (T2DM), and impaired fasting glucose (IFG) were assessed. Serum dinitroaniline herbicides including benfluralin, trifluralin, and pendimethalin were measured. T2DM-related polygenic risk score (PRS) and healthy life scores were constructed. RESULTS: Cross-sectionally, each 2-fold increase in serum benfluralin was associated with a 1.12%, 2.03%, and 9% increase in FPG, HOMA-IR, and IFG risk, respectively. Each 2-fold increase in serum trifluralin was associated with a 0.70% increase in FPG. Each 2-fold increase in serum pendimethalin was associated with a 2.53% and 24% increase in FPG and IFG risk, respectively (all P < 0.05). Positive associations were found between the dinitroaniline herbicide mixture and glucose dysregulation. Longitudinally, serum benfluralin and pendimethalin were associated with the annual increases in FPG and HOMA-IR (P < 0.05). Joint and interaction effect analysis showed that compared with participants with high benfluralin/trifluralin/pendimethalin, high PRS, and unhealthy lifestyle, those with low benfluralin/trifluralin/pendimethalin, low PRS, and healthy lifestyle showed the greatest declines in FPG, i.e., -15.46%, -13.58%, and -10.51% changes, respectively; and the greatest reductions in IFG risks, i.e., 75%, 61%, and 73% reductions, respectively (all P < 0.05). CONCLUSIONS: This study highlighted the importance of controlling dinitroaniline herbicide exposure and following healthy lifestyles in glucose dysregulation prevention, especially among individuals with high genetic risk of T2DM.

Comparison of estimated glomerular filtration rate using five equations to predict acute kidney injury following hip fracture surgery.

BACKGROUND: Decreased estimated glomerular filtration rate (eGFR) is associated with acute kidney injury (AKI) following hip fracture surgery. Delaying surgery for preoperative treatment of comorbidities is controversial in this patient population. The purpose of this study was 1) to assess differences in demographics and comorbidities between AKI and non-AKI groups, 2) to analyze equations used in calculating eGFR, and 3) to identify the equation which best predicts the development of AKI following hip fracture surgery. We hypothesize that one of the equations used to calculate eGFR will be superior to the others. PATIENTS AND METHODS: 124,002 cases of hip fracture surgery were performed from 2012 to 2019, based upon a query of the National Surgical Quality Improvement Program (NSQIP). Preoperative eGFR was calculated using the following: Modification of Diet in Renal Disease (MDRD) II, re-expressed MDRD II, Chronic Kidney Disease Epidemiology Collaboration, Mayo quadratic, and Cockcroft-Gault equations. Independent associations between preoperative eGFR and postoperative renal failure were evaluated using multivariate regression analysis. The predictive ability of each equation was determined using the Akaike information criterion (AIC). RESULTS: AKI was diagnosed in 584 (0.71%) out of the 82,326 patients following hip fracture surgery. The AKI and no AKI cohorts differed significantly by patient sex (p = <0.001), race (p = <0.001), BMI (p = < 0.001), preoperative hematocrit (p = <0.001), preoperative albumin (p = <0.001), diabetes mellitus (p = <0.001), hypertension (p = <0.001), and congestive heart failure (p = <0.001). The Mayo equation (84.0 ± 23.7) was the equation with the highest calculated mean eGFR, followed by the CKD-EPI equation (83.6 ± 20.0), MDRD II equation (83.0 ± 38.9), CG equation (74.7 ± 35.5), and finally the re-expressed MDRD II equation (68.5 ± 36.0) which had the lowest calculated mean eGFR.. All five equations detected that a decrease in preoperative eGFR was associated with an increased risk of postoperative AKI. Lower preoperative eGFR, as calculated by each of the five equations, was significantly associated with an increased risk of AKI following surgical fixation of hip fracture. The AIC was the lowest in the Mayo equation, demonstrating the best fit of the equations to predict postoperative AKI CONCLUSIONS: We propose that using the equation that best identifies those at risk of developing postoperative AKI may help with perioperative decision making and treatment to improve outcomes, which we found to be the Mayo equation. The risk of postoperative AKI was independently associated with decreased preoperative eGFR. The results of this study may warrant further investigation utilizing prospective studies. LEVEL OF EVIDENCE: III; retrospective cohort study.

Association of early- and late-life bipolar disorder with incident dementia. A Danish cohort study.

BACKGROUND: This study aimed to explore the association between bipolar disorder and the risk of developing dementia, and whether the risk varies with age at the onset of bipolar disorder. METHODS: In this study, 37,084 individuals with a first-time diagnosis of bipolar disorder diagnosed between 1969 and 2018 and a reference population (n = 189,662) matched on sex, birth year and time of bipolar diagnosis (index date) were followed in nationwide registries for incident dementia until October 2020. Associations were analysed using Cox proportional hazard regression with adjustment for sex, education level, alcohol or drug abuse, traumatic brain injury, ischemic heart disease, stroke and diabetes mellitus. RESULTS: In total, 6.6 % of individuals with bipolar disorder and 4.0 % in the reference population developed dementia during the mean follow-up of 13.1 years. Compared to the reference population, individuals with bipolar disorder had a higher incidence of dementia during follow-up after adjusting for potential confounders (HR: 2.66, 95 % CI [2.53-2.79]). The strength of this association did not vary among individuals diagnosed with bipolar disorder before and after age 45. LIMITATIONS: The higher risk of dementia identified for individuals with bipolar disorder could be influenced by detection bias and, despite a large cohort, some of the age-stratified analyses were still affected by lack of statistical power. CONCLUSION: Individuals with bipolar disorder have a higher risk of developing dementia compared to a reference population without bipolar disorder, independent of the age at the onset of bipolar disorder.

SLEEP APNEA IS A COMMON AND DANGEROUS CARDIOVASCULAR RISK FACTOR.

Sleep apnea involves almost one billion individuals throughout the world, including 40 million Americans. Of major medical concern is the fact that the prevalence of sleep apnea is significantly increasing due to the epidemic of obesity, physical inactivity, and diabetes mellitus which are important risk factors for the development and persistence of sleep apnea in individuals. Sleep apnea is characterized by multiple episodes of apnea or hypopnea during sleep, which cause nocturnal arousals, gasping for breath during the night, daytime sleepiness, irritability, forgetfulness, fatigue and recurrent headaches. Obstructive sleep apnea occurs when upper airway obstruction occurs in an individual during sleep with absent or markedly reduced airflow in the presence of continued activity of inspiratory thoracic and diaphragmatic muscles. Central sleep apnea is defined as the absence or the significant reduction of naso-oral airflow due to the withdrawal during sleep of ponto-medullary respiratory center stimulation of the nerves of the inspiratory thoracic and diaphragmatic muscles and absence of contraction of these muscles during apnea. Complex sleep apnea occurs when an individual exhibits characteristics of both obstructive and central sleep apnea. The severity of sleep apnea is measured by polysomnography and the apnea hypopnea index (AHI), which is the average number of apneas and hypopneas per hour of sleep measured by polysomnography. Sleep apnea is mild if the AHI is 5-14/hour with no or mild symptoms, moderate if the AHI is 15 to 30/hour with occasional daytime sleepiness, and severe if the AHI is >30/hour with frequent daytime sleepiness that interferes with the normal activities of daily life. Chronic sleep apneas and hypopneas followed by compensatory hyperpneas are associated with significant adverse cardiovascular consequences including: 1) recurrent hypoxemia and hypercarbia; 2) Increased sympathetic nerve activity and decreased parasympathetic nerve activity; 3) oxidative stress and vascular endothelial dysfunction; and 4) cardiac remodeling and cardiovascular disease. Moderate or severe sleep apnea significantly increases the risk of coronary artery disease, congestive heart failure, cerebral vascular events (strokes), and cardiac dysrhythmias, and also increase the morbidity and mortality of these diseases. Nevertheless, sleep apnea is currently underdiagnosed and untreated in many individuals due to the challenges in the prediction and detection of sleep apnea and a lack of well-defined optimal treatment guidelines. Chronic continuous positive airway pressure for ≥4 hours/night for >70% of nights is beneficial in the treatment of patients with sleep apnea. CPAP Improves sleep quality, reduces the AHI, augments cardiac output and increases oxygen delivery to brain and heart, reduces resistant hypertension, decreases cardiac dysrhythmias, and reduces daytime sleepiness. The present article discusses the diagnosis of obstructive sleep apnea, central sleep apnea, and complex apnea. Thereafter the important pathophysiologic mechanisms in sleep apnea and the relationship of these pathophysiologic mechanics to atherosclerotic vascular disease are reviewed. Guidelines are then provided for the treatment of mild, moderate and severe sleep apnea In order to reduce the cardiovascular morbidity and mortality caused by sleep apnea and facilitate the diagnosis and the long-term, effective treatment of sleep apnea in patients, the close cooperation is necessary of cardiovascular specialists, pulmonary specialists, and respiratory therapy/ rehabilitation specialists.