Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Dietary free L-glutamate contributes to maintaining a low sodium intake among Vietnamese.

Background: The World Health Organization (WHO) and the Food and Agriculture Organization (FAO) recommend the consumption of less than 2,000 mg of sodium/day to reduce blood pressure and the risk of conditions such as cardiovascular disease and coronary heart disease. The sodium intake among Vietnamese was reported to be 7,200 mg/d or more. Free L-glutamate enhances flavor when it is added to food and improves the taste of sodium-reduced foods. Objective: This study aims to investigate whether the intake of free L-glutamate-rich seasonings contributes to maintaining a low sodium intake in a cross-over study. Methods: From a total of 145 subjects, 42 participants were screened for participation in the cross-over design study. Subjects were randomly allocated to the Low free L-glutamate group (Low free L-Gl) and the Normal free L-glutamate group (Normal free L-Gl). Both received a direct educational guideline to reduce sodium intake. The Low free L-Gl group started with a restriction in the variety of free L-glutamate-rich seasonings, and the Normal free L-Gl group had no restriction in the variety of seasonings. Blood pressure was measured at week 0 (baseline), week 2, week 4, and week 6, while body weight, height, urine sodium and potassium excretion, chromogranin-A (CgA pmol/mg protein) from saliva, and free L-glutamate from food were measured at week 0, week 3, and week 6. Results: In Low free L-Gl, the amount of free L-glutamate in food decreased significantly from baseline to week 6 (p < 0.00), while it did not change in the Normal free L-Gl (p > 0.05). However, the reduction of sodium excretion at week 6 was 22% in Low free L-Gl (5,875 mg/d vs. 4,603 mg/d, p < 0.01) and 46% in Normal free L-Gl (6,107 mg/d vs. 3,277 mg/d, p < 0.00), both lower than the baseline. CgA (pmol/mg protein) did not show any difference between the two groups. Conclusion: The group with Normal free L-Gl intake showed a 46% reduction in sodium excretion by week 6 compared to the baseline. This suggests that the consumption of L-glutamate-rich seasonings when complemented with direct educational guidelines, can contribute to maintaining a low sodium intake.

Exosomal TNF-α mediates voltage-gated Na+ channels 1.6 overexpression and contributes to brain-tumor induced neuronal hyperexcitability.

Patients affected by glioma frequently suffer of epileptic discharges, however the causes of brain tumor-related epilepsy (BTRE) are still not completely understood. We investigated the mechanisms underlying BTRE by analyzing the effects of exosomes released by U87 glioma cells and by patient-derived glioma cells. Rat hippocampal neurons incubated for 24 h with these exosomes exhibited increased spontaneous firing, while their resting membrane potential shifted positively by 10-15 mV. Voltage clamp recordings demonstrated that the activation of the Na+ current shifted towards more hyperpolarized voltages by 10-15 mV. To understand the factors inducing hyperexcitability we focused on exosomal cytokines. Western Blot and ELISA assays show that TNF-α is present inside glioma-derived exosomes. Remarkably, incubation with TNF-α fully mimicked the phenotype induced by exosomes, with neurons firing continuously, while their resting membrane potential shifted positively. RT-PCR revealed that both exosomes and TNF-α induced over-expression of the voltage-gated Na channel Nav1.6, a low-threshold Na+ channel responsible for hyperexcitability. When neurons were preincubated with Infliximab, a specific TNF-α inhibitor, the hyperexcitability induced by exosomes and TNF-α were drastically reduced. We propose that Infliximab, an FDA approved drug to treat rheumatoid arthritis, could ameliorate the conditions of glioma patients suffering of BTRE.

Treatment of Metabolic (Dysfunction)-Associated Fatty Liver Disease: Evidence from Randomized Controlled Trials-A Short Review.

Metabolic-associated fatty liver disease (MALFD) is a highly prevalent and progressive disease, strongly related to obesity, metabolic syndrome, and cardiovascular disease. It comprises a spectrum of liver pathology from steatosis (fat accumulation in the hepatocytes) to steatosis with inflammation (metabolic-associated steatohepatitis, MASH), fibrosis, cirrhosis, and hepatocellular carcinoma. There is currently only one medication, resmetirom, US Food and Drug Administration approved for the treatment of MALFD. Evidence from randomized trials supports the efficacy of hypocaloric diets and exercise in MASH resolution. Moreover, substantial weight loss after bariatric surgery can lead to significant and longitudinally sustained MASH resolution, improvement in liver fibrosis, and decrease in the risk of major cardiovascular adverse events. Pioglitazone, an insulin sensitizer, initiated at the early stages, before the progression to fibrosis, may be effective in resolution of MASH in patients with or without type 2 diabetes. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs), semaglutide and liraglutide, may also be effective in resolution of MASH but not of fibrosis. Preliminary data from interventions with tirzepatide, a dual GLP-1 and glucose-dependent insulinotropic polypeptide RA, and sodium-glucose cotransporter 2 inhibitors are encouraging, but more data based on liver biopsy are needed.

In-hospital initiation of sodium-glucose cotransporter-2 inhibitors in patients with heart failure and reduced ejection fraction: 90-day prescription patterns and clinical implications.

INTRODUCTION: Safety and early clinical benefit make sodium-glucose cotransporter-2 inhibitor (SGLT2-i) therapy suitable for in-hospital initiation in patients with heart failure and reduced ejection fraction (HFrEF). Despite randomized controlled trials and guideline recommendations, they are underused, and clinical inertia may play a role. OBJECTIVES: PRIMARY: To assess the impact of initiating SGLT-2i at discharge on 90-day prescription rates in patients with HFrEF during hospitalization for acute heart failure (AHF). Secondary: To evaluate the presence of independent factors associated with prescription, and to explore clinical outcomes at 90 days. METHODS: Retrospective analysis of a consecutive prospective single-center cohort. Adult patients hospitalized between January 2021 and September 2022 with a primary diagnosis of AHF and left ventricular ejection fraction (LVEF) <40% were included. The primary outcome was SGLT2-i prescription rate at 90 days, and the exploratory secondary endpoints was the composite of hospitalization or urgent visit for AHF or all-cause mortality at 90 days. RESULTS: 237 patients were included. Mean age was 76±11 years, and mean LVEF was 29±7%. In patients without contraindications, SGLT2 inhibitors (SGLT2-i) were prescribed during hospitalization in 52.3%. At 90 days, the SGLT2-i prescription rate was 94.2% in those with in-hospital initiation and 14.4% in those without. (p<0.001). Independent factor associated with inpatient prescription was lower LVEF, 0.83 (95% CI: 0.77-0.89) for each point. Patients with in-hospital SGLT2-i initiation showed a lower rate of the combined endpoint of all-cause death, HF rehospitalization, or unplanned HF visit at 90 days (44.4% versus 23.9%, p=0.005). CONCLUSIONS: In-hospital initiation of SGLT-2-i was associated with significantly higher prescription rates and lower prevalence in the secondary combined endpoint at 90 days. This study reflects the presence of medical inertia, particularly in patients with higher LVEF, and highlights the hospitalization period as an optimal time to start SGLT2-i.

Waste newspaper as cellulose resource of activated carbon by sodium salts for methylene blue and congo red removal.

The work was aimed at evaluating the adsorptive properties of waste newspaper (WN) activated carbons chemically produced using sodium salts for methylene blue (MB) and congo red (CR) removal. The activated carbons, designated as AC1, AC2, AC3 and AC4 were prepared through impregnation with NaH2PO4, Na2CO3, NaCl and NaOH, respectively and activation at 500 °C for 1 h. The activated carbons were characterized for surface chemistry, thermal stability, specific area, morphology and composition. The AC1 with a surface area of 917 m2/g exhibits a greater MB capacity of 651 mg/g. Meanwhile, a greater CR capacity was recorded by AC2 at 299 mg/g. The pseudo-second order model fitted well with the kinetic data, while the equilibrium data could be described by Langmuir model. The thermodynamic parameters, i.e.., positive ΔH°, negative ΔG° and positive ΔS° suggest that the adsorption of dyes is endothermic, spontaneous and feasible at high solution temperature. To conclude, WN is a potential cellulose source for producing activated carbon, while NaH2PO4 activation could be employed to convert WN into activated carbon for effective dye wastewater treatment.

Stabilizing Interlayer Repulsion in Layered Sodium-Ion Oxide Cathodes via Hierarchical Layer Modification.

Layered sodium-ion oxides hold considerable promise in achieving high-performance sodium-ion batteries. However, the notorious phase transformation during charging, attributed to increased O2-─O2- repulsion, results in substantial performance decay. Here, a hierarchical layer modification strategy is proposed to stabilize interlayer repulsion. During desodiation, migrated Li+ from the transition metal layer and anchored Ca2+ in sodium sites maintain the cationic content within the sodium layer. Meanwhile, partial oxygen substitution by fluorine and the involvement of oxygen in redox reactions increase the average valence of the oxygen layer. This sustained cation presence and elevated anion valence collectively mitigate increasing O2-─O2- repulsion during sodium extraction, enabling the Na0.61Ca0.05[Li0.1Ni0.23Mn0.67]O1.95F0.05 (NCLNMOF) cathode to retain a pure P2-type structure across a wide voltage range. Unexpected insights reveal the interplay between different doping elements: the robust Li─F bonds and Ca2+ steric effects suppressing Li+ loss. The NCLNMOF electrode exhibits 82.5% capacity retention after 1000 cycles and a high-rate capability of 94 mAh g-1 at 1600 mA g-1, demonstrating the efficacy of hierarchical layer modification for high-performance layered oxide cathodes.

[Ion chromatography-pulsed amperometry method for determination of trace hydrogen sulfide in air].

Hydrogen sulfide (H2S) is a pervasive gaseous pollutant that emits the characteristic odor of rotten gas, even at low concentrations. It is generated during various industrial processes, including petroleum and natural gas refining, mining operations, wastewater treatment activities, and refuse disposal practices. According to statistics from the World Health Organization (WHO), over 70 occupations are exposed to H2S, rendering it a key monitoring factor in occupational disease detection. Although H2S has legitimate uses in the chemical, medical, and other fields, prolonged exposure to this gas can cause severe damage to the respiratory and central nervous systems, as well as other organs in the human body. Moreover, the substantial release of H2S into the environment can lead to significant pollution. This noxious substance has the potential to impair soil, water, and air quality, while disrupting the equilibrium of the surrounding ecosystems. Therefore, sulfide has become one of the most commonly measured substances for environmental monitoring worldwide. Achieving the stable enrichment and accurate detection of low-level H2S is of great significance. Common methods for detecting this gas include spectrophotometry, chemical analysis, gas chromatography, rapid field detection, and ion chromatography. Although these methods provide relatively reliable results, they suffer from limitations such as high detection cost, low recovery, lack of environmental friendliness, and imprecise quantification of low-concentration H2S. Furthermore, the sampling processes involved in these methods are complex and require specialized equipment and electrical devices. Additionally, approximately 20% of the sulfides in a sample are lost after 2 h in a conventional alkaline sodium hydroxide solution, causing difficulties in preservation and detection. In this study, an accurate, efficient, and cost-saving method based on ion chromatography-pulse amperometry was developed for H2S determination. A conventional IonPac AS7 (250 mm×4 mm) anion-exchange column was employed, and a new eluent based on sodium hydroxide and sodium oxalate was used to replace the original sodium hydroxide-sodium acetate eluent. The main factors influencing the separation and detection performance of the proposed method, including the pulse amperage detection potential parameters and integration time, as well as the type and content of additives in the stabilizing solution, were optimized. The results showed that the proposed method had a good linear relationship between 10 and 3000 µg/L, with correlation coefficients (r2) of up to 0.999. The limits of detection (S/N=3) and quantification (S/N=10) were 1.53 and 5.10 µg/L, respectively. The relative standard deviations (RSDs) of the peak area and retention time of sulfides were less than 0.2% (n=6). The new method exhibited excellent stability, with up to 90% reduction in reagent costs. Compared with conventional ion chromatography-pulse amperometry, this method is more suitable for detecting low concentrations of sulfides in actual samples. Sulfides in a 250 mmol/L sodium hydroxide-0.8% (mass fraction) ethylenediaminetetraacetic acid disodium salt solution were effectively maintained for over 10 h. The new stabilizer significantly improved the reliability of both large-scale and long-term detection. The recovery of the proposed method was investigated by combining the system with a badge-type passive sampler. This sampling method requires no power devices; it is inexpensive, simple to operate, and can realize long-term sampling without the need for skilled personnel. Moreover, it can overcome the influence of short-term changes in pollutant concentration. The sampling results have high reference value for large-scale intervention-less pollutant monitoring in ultraclean rooms, museum counters, and other places. The results demonstrated that the recovery of the proposed method was greater than 95% for the blank sample and 80% for the sample plus standard solution. Finally, the newly established method was applied to determine H2S levels in air samples collected via passive sampling at school garbage stations. The measured results did not exceed the national limit.

[Determination of sodium cyclamate in Baijiu by pre-column derivatization-high performance liquid chromatography with fluorometric detection].

Sodium cyclamate in Baijiu is a key item in the China National Food Safety Supervision and Inspection Plan. A simple, economical, sensitive, and reliable method is urgently needed for routine analysis and internal quality control. A method based on high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed for the determination of sodium cyclamate in Baijiu by o-phthalaldehyde derivatization. First, the sodium cyclamate in the sample solution was converted into amino compounds using the desulfurization reaction under acidic conditions. Next, 400 g/L sodium hydroxide solution was added to the sample solution for neutralization. The amino compounds in the sample solution were then derivatized with o-phthalaldehyde to produce indole-substituted derivatives that are capable of producing fluorescence signals. Separation was carried out on a C18 column (250 mm×4.6 mm, 5 µm) in isocratic elution mode using a mobile phase consisting of acetonitrile and phosphate buffer. Finally, the eluate was monitored using a fluorescence detector, and an external standard method was used for quantification. A good linear relationship was obtained in the range of 0.1-2.0 mg/L, with correlation coefficients greater than 0.999. The average recoveries of sodium cyclamate spiked at levels of 0.1-1.0 mg/kg in Baijiu samples ranged from 90.7% to 100.9%, with relative standard deviations (RSDs) of 3.5%-5.6% (n=6). The limits of detection and quantification were 0.03 and 0.10 mg/kg, respectively. Nine Baijiu samples collected from the market were tested, and the results demonstrated that the contents of sodium cyclamate detected by the developed method were consistent with those obtained using the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method described in GB 5009.97-2016 (the third method). The proposed method is economical, sensitive, specific, and accurate; thus, it provides a basic approach for the determination of sodium cyclamate in Baijiu samples and has great potential for routine analysis in foodstuffs.

A facile synthesis of 2-(4-((4-chlorophenyl)(hydroxy)methyl) phenoxy)-2-methylpropanoic acid: Metabolite of anti-hyperlipidemic drug Fenofibrate.

Synthesis and characterization of drug metabolites has emerged as an important area of research in consideration to the significant contribution of studies on metabolites in drug research. The present work comprises synthesis of 2-(4-((4-chlorophenyl)(hydroxy)methyl) phenoxy)-2-methylpropanoic acid, a metabolite of anti-hyperlipidemic drug fenofibrate. The desired compound was prepared by two different synthetic routes. The ketone group of fenofibric acid was reduced using sodium borohydride in one route whereas the hydrolysis of isopropyl ester of the reduced fenofibrate was achieved by the mild alkaline hydrolysis in the other path. Both the ways of synthesis furnished the desired compound in excellent yield and purity. The new synthetic congener was characterized by spectroscopic methods.

Clinical value of Vitamin-D combined with budesonide/formoterol and theophylline sodium glycinate sustained-release tablets in the treatment of chronic obstructive pulmonary disease patients.

Objective: To explore the clinical value of Vitamin-D combined with budesonide/formoterol (BF) and theophylline sodium glycinate (TSG) sustained-release tablets in the treatment of patients with chronic obstructive pulmonary disease (COPD). Methods: Medical records of 114 patients with CODP, treated in Wenzhou Geriatric Hospital from October 2020 to February 2023, were retrospectively analyzed. Of them, 59 received treatment with Vitamin-D combined with BF and TSG sustained-release tablets (Group-A), and 55 patients received treatment with BF combined with TSG sustained-release tablets (Group-B). Lung function indicators, blood gas status, inflammatory factors, fractional exhaled nitric oxide (FeNO), and 25-hydroxyvitamin D [25(OH)D] levels before and after the treatment in both groups were collected. Results: After the treatment, lung function indicators, blood gas status, inflammatory factors, FeNO, and 25 (OH) D levels in both groups were significantly improved compared to pretreatment levels, and were significantly better in the Group-A compared to Group-B (P<0.05). Conclusions: The combination of Vitamin-D, BF, and TSG sustained-release tablets can effectively regulate the blood gas status of patients with COPD, improve lung function, regulate FeNO and 25 (OH) D, and effectively downregulate the levels of inflammatory factors, thus reducing the degree of inflammatory response.

Short-Term Outcomes of Patients With Hyponatremia Presenting to the Emergency Department: An Observational Study.

BACKGROUND: Hyponatremia is the predominant electrolyte imbalance disorder in the emergency department. It can manifest with a diverse array of symptoms, ranging from non-specific and moderate to severe and even life-threatening. There is a scarcity of literature addressing the clinical characteristics and prognosis of patients with hyponatremia presenting to the emergency department in the western part of Rajasthan. The objective of this study was to investigate the impact of hyponatremia on the outcomes of patients presenting to the emergency department. METHODS: In this prospective, cross-sectional, observational study, 200 patients aged more than 18 years who presented to the emergency department with serum sodium < 135 mEq/l were included. The triage of patients was determined by their primary complaints. The primary outcome was to study the clinical profile of patients with hyponatremia presenting to the emergency department. The secondary outcomes were to examine the etiology, i.e., hypovolemic, euvolemic, or hypervolemic, and the outcome of patients on the 7th day (patient admitted to the ward or intensive care unit) and the 28th day (discharged or death) with hyponatremia presenting to the emergency department. The clinical status of the patients was noted by telephonic follow-up in case they were not admitted for this period. RESULTS: Out of 200 patients, 66 (33%) had hypovolemic, 96 (48%) had euvolemic, and 38 (19%) had hypervolemic hyponatremia. We observed that seizures (84.2%), confusion (56%), and coma (77.7%) were the most common clinical features of patients with severe hyponatremia in the emergency, which was statistically significant than mild and moderate hyponatremia (p = 0.03, 0.023, and 0.029, respectively). On the 7th day of hospitalization, out of 181 (90.5%) admissions in the ward, 116 (64.08%) had severe hyponatremia, and out of 19 (9.5%) ICU admissions, 13 (68.4%) had severe hyponatremia. Death was seen in five (2.5%) patients, one (20%) in moderate and four (80%) in severe hyponatremia cases. CONCLUSION: Most cases of hyponatremia in this study were euvolemic. Most patients experienced severe hyponatremia, and seizures, confusion, and coma were the most prevalent symptoms. These disorders must be recognized early to properly diagnose and treat hyponatremia and prevent its morbidity and death.

Air-Stable High-Entropy Layered Oxide Cathode with Enhanced Cycling Stability for Sodium-Ion Batteries.

O3-type layered oxides have been extensively studied as cathode materials for sodium-ion batteries due to their high reversible capacity and high initial sodium content, but they suffer from complex phase transitions and an unstable structure during sodium intercalation/deintercalation. Herein, we synthesize a high-entropy O3-type layered transition metal oxide, NaNi0.3Cu0.05Fe0.1Mn0.3Mg0.05Ti0.2O2 (NCFMMT), by simultaneously doping Cu, Mg, and Ti into its transition metal layers, which greatly increase structural entropy, thereby reducing formation energy and enhancing structural stability. The high-entropy NCFMMT cathode exhibits significantly improved cycling stability (capacity retention of 81.4% at 1C after 250 cycles and 86.8% at 5C after 500 cycles) compared to pristine NaNi0.3Fe0.4Mn0.3O2 (71% after 100 cycles at 1C), as well as remarkable air stability. Finally, the NCFMMT//hard carbon full-cell batteries deliver a high initial capacity of 103 mAh g-1 at 1C, with 83.8 mAh g-1 maintained after 300 cycles (capacity retention of 81.4%).

Improvements in daytime sleepiness and disrupted nighttime sleep with once-nightly sodium oxybate in people with narcolepsy type 1 and type 2: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain language summary of a published article in the journal Sleep. Narcolepsy is a sleep condition that has 2 different subtypes: narcolepsy type 1 and narcolepsy type 2. These are called NT1 and NT2 for short. Sodium oxybate (SXB) is approved to treat excessive daytime sleepiness (EDS) and cataplexy. People with NT1 and NT2 both have EDS, but cataplexy is only present in people with NT1. Limited information is available about how SXB works in people with NT2. This is because previous trials have included only people with NT1 or people with unspecified narcolepsy. For more than 20 years, the only available formulation of this medicine had to be given twice during the night. Many people with narcolepsy find that chronically waking up in the middle of the night for a second dose of SXB is disruptive to themselves or others in their household. People have also reported sleeping through alarm clocks, missing their second dose, and feeling worse the next day. Some people have accidentally taken the second dose too early, putting them at risk for serious adverse effects. These adverse effects may include slow breathing, low blood pressure, or sedation. The US Food and Drug Administration (FDA) approved a medicine called LUMRYZ™ (sodium oxybate) for extended-release oral suspension in May 2023. LUMRYZ is a once-nightly formulation of SXB (ON-SXB for short) and is taken as a single dose before bedtime. This medicine treats EDS and muscle weakness (also known as cataplexy) in people with narcolepsy. A clinical trial called REST-ON studied ON-SXB to find out if it was better at treating narcolepsy symptoms than a medicine with no active ingredients (placebo). This summary describes a study that tested whether ON-SXB was better than placebo at treating narcolepsy symptoms in people with NT1 or NT2. WHAT WERE THE RESULTS?: This study showed that compared to people who took placebo, people who took ON-SXB were able to stay awake longer during the day, felt less sleepy during the daytime, had less cataplexy, and had more improvements in their symptoms overall than people who took placebo. WHAT DO THE RESULTS MEAN?: ON-SXB has been proven effective for people with NT1 or NT2. Unlike prior formulations of SXB, ON-SXB is taken once at bedtime, without requiring waking up in the middle of the night for a second dose.

Borate bioactive glass enhances 3D bioprinting precision and biocompatibility on a sodium alginate platform via Ca2+ controlled self-solidification.

Sodium alginate (SA) has gained widespread acclaim as a carrier medium for three-dimensional (3D) bioprinting of cells and a diverse array of bioactive substances, attributed to its remarkable biocompatibility and affordability. The conventional approach for fabricating alginate-based tissue engineering constructs entails a post-treatment phase employing a calcium ion solution. However, this method proves ineffectual in addressing the predicament of low precision during the 3D printing procedure and is unable to prevent issues such as non-uniform alginate gelation and substantial distortions. In this study, we introduced borate bioactive glass (BBG) into the SA matrix, capitalizing on the calcium ions released from the degradation of BBG to incite the cross-linking reaction within SA, resulting in the formation of BBG-SA hydrogels. Building upon this fundamental concept, it unveiled that BBG-SA hydrogels greatly enhance the precision of SA in extrusion-based 3D printing and significantly reduce volumetric contraction shrinkage post-printing, while also displaying certain adhesive properties and electrical conductivity. Furthermore, in vitro cellular experiments have unequivocally established the excellent biocompatibility of BBG-SA hydrogel and its capacity to actively stimulate osteogenic differentiation. Consequently, BBG-SA hydrogel emerges as a promising platform for 3D bioprinting, laying the foundation for the development of flexible, biocompatible electronic devices.

Sodium butyrate improves renal injury in diabetic nephropathy through AMPK/SIRT1/PGC-1α signaling pathway.

Diabetic nephropathy (DN) is a prototypical chronic energy metabolism imbalance disease. The AMPK/Sirt1/PGC-1α signaling pathway plays a pivotal role in regulating energy metabolism throughout the body. Gut microbiota ferment indigestible carbohydrates to produce a variety of metabolites, particularly short-chain fatty acids (SCFAs), which exert positive effects on energy metabolism. However, the potential for SCFAs to ameliorate DN-associated renal injury via the AMPK/Sirt1/PGC-1α pathway remains a matter of debate. In this study, we investigated the effects of sodium butyrate (NaB), a SCFA, on energy metabolism in mice with spontaneous DN at two different doses. Body weight, blood glucose and lipid levels, urinary protein excretion, liver and kidney function, interleukin-6 (IL-6) levels, and the expressions of AMPK, phosphorylated AMPK (p-AMPK), mitofusin 2 (MFN2), optic atrophy 1 (OPA1), and glucagon-like peptide-1 receptor (GLP-1R) were monitored in mice. Additionally, butyrate levels, gut microbiota composition, and diversity in colonic stool were also assessed. Our findings demonstrate that exogenous NaB supplementation can improve hyperglycemia and albuminuria, reduce renal tissue inflammation, inhibit extracellular matrix accumulation and glomerular hypertrophy, and could alter the gut microbiota composition in DN. Furthermore, NaB was found to upregulate the expressions of MFN2, OPA1, p-AMPK, and GLP-1R in DN renal tissue. These results suggest that NaB could improve the composition of gut microbiota in DN, activate the AMPK/Sirt1/PGC-1α signaling pathway, and enhance mitochondrial function to regulate energy metabolism throughout the body. Collectively, our findings indicate that NaB may be a novel therapeutic agent for the treatment of DN.

Kidney and cardiovascular-protective benefits of combination drug therapies in chronic kidney disease associated with type 2 diabetes.

Given the substantial burden of chronic kidney disease associated with type 2 diabetes, an aggressive approach to treatment is required. Despite the benefits of guideline-directed therapy, there remains a high residual risk of continuing progression of chronic kidney disease and of cardiovascular events. Historically, a linear approach to pharmacologic management of chronic kidney disease has been used, in which drugs are added, then adjusted, optimized, or stopped in a stepwise manner based on their efficacy, toxicity, effects on a patient's quality of life, and cost. However, there are disadvantages to this approach, which may result in missing a window of opportunity to slow chronic kidney disease progression. Instead, a pillar approach has been proposed to enable earlier treatment that simultaneously targets multiple pathways involved in disease progression. Combination therapy in patients with chronic kidney disease associated with type 2 diabetes is being investigated in several clinical trials. In this article, we discuss current treatment options for patients with chronic kidney disease associated with type 2 diabetes and provide a rationale for tailored combinations of therapies with complementary mechanisms of action to optimize therapy using a pillar-based treatment strategy. [This article includes a plain language summary as an additional file].

Trends in utilization patterns of newer glucose-lowering drugs in US adults with type 2 diabetes and a history of coronary heart disease or heart failure: 2005-2019.

BACKGROUND: The newer glucose-lowering drugs (GLDs), including Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i), have demonstrated superior cardio- and renal protective benefits compared to older GLDs in individuals with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). OBJECTIVE: This study examined the trends of the newer GLDs use in people with T2D who had a history of coronary heart disease or heart failure in the United States. METHOD: We used 2005-2019 data from the Medical Expenditure Panel Survey (MEPS). Individuals with self-reported diabetes and CVD history were identified. RESULTS: There was a steady increase in the use of GLP-1RA only from 2008 (3 %) to 2019 (21 %) and SGLT2i only from 2014 (5 %) to 2019 (12 %). Individuals with dual use of both newer GLD classes increased from 0.62 % in 2015 to 6 % in 2019. The overall uptake of these two newer drugs in 2019 was less than 40 %. In other words, 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments. CONCLUSION: The use of GLP-1RA and SGLT2i among individuals with T2D and a history of CVD was low and varied by insurance type. Policy-level interventions are needed to improve the use of these newer treatments further. SUMMARY: We examined how newer glucose-lowering drugs are used among individuals with type 2 diabetes and at high risk for coronary heart disease or heart failure in the US. We found that 60 % of individuals who can substantially benefit from these newer treatments did not use the treatments due to the variation of insurance type.

Injectable chitosan hydrogel effectively controls lesion growth in a venous malformation murine model.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of intralesional injection of chitosan hydrogel (CH) combined with sodium tetradecyl sulfate (STS) to sclerose and embolize venous malformations (VMs) by comparison with 3% STS foam and placebo in a mouse model. MATERIALS AND METHODS: Subcutaneous VMs were created by injecting HUVEC_TIE2-L914F cells, mixed with matrigel, into the back of athymic mice (Day [D] 0). After VM-like lesions were established at D10, 70 lesions were randomly assigned to one of six treatment groups (untreated, saline, 3% STS-foam, CH, 1% STS-CH, 3% STS-CH). For 3% STS-foam, the standard Tessari technique was performed. VMs were regularly evaluated every 2-3 days to measure lesion size until the time of collection at D30 (primary endpoint). At D30, VM lesions including the matrigel plugs were culled and evaluated by histological analysis to assess vessel size, chitosan distribution and endothelial expression. One-way analysis of variance (ANOVA) test was performed to compare quantitative variables with normal distribution, otherwise Kruskal-Wallis test followed by pairwise comparisons by a Wilcoxon rank sum test was performed. RESULTS: All VMs were successfully punctured and injected. Six VMs injected with 3% STS-CH showed early skin ulceration with an extrusion of the matrigel plug and were excluded from final analysis. In the remaining 64 VMs, skin ulceration occurred on 26 plugs, resulting in the loss of three 3% STS-foam and one 1% STS-CH plugs. Both chitosan formulations effectively controlled growth of VMs by the end of follow-up compared to untreated or 3% STS-foam groups (P < 0.05). Vessel sizes were smaller with both CH formulations compared to untreated and saline groups (P < 0.05). Additionally, there were smaller vascular channels within the 1% STS-CH group compared to the 3% STS-foam group (P < 0.05). CONCLUSION: Chitosan's ability to control the growth of VMs suggests a promising therapeutic effect that outperforms the gold standard (STS-foam) on several variables.