Transcriptome wide changes in long noncoding RNAs in diabetic ischemic heart disease.

More than 10% of adults in the United States have type 2 diabetes mellitus (DM) with a 2-4 times higher prevalence of ischemic heart disease than the non-diabetics. Despite extensive research approaches to limit this life-threatening condition have proven unsuccessful, highlighting the need for understanding underlying molecular mechanisms. Long noncoding RNAs (lncRNAs), which regulate gene expression by acting as signals, decoys, guides, or scaffolds have been implicated in diverse cardiovascular conditions. However, their role in ischemic heart disease in DM remains poorly understood. We provide new insights into the lncRNA expression profile after ischemic heart disease in DM mice. We performed unbiased RNA sequencing of well-characterized type 2 DM model db/db mice or its control db/+ subjected to sham or MI surgery. Computational analysis of the RNA sequencing of these LV tissues identified several differentially expressed lncRNAs between (db/db sham vs. db/db MI) including Gm19522 and Gm8075. lncRNA Gm-19522 may regulate DNA replication via DNA protein kinases, while lncRNA Gm-8075 is associated with cancer gene dysregulation and PI3K/Akt pathways. Thus, the downregulation of lncRNAs Gm19522 and Gm8075 post-MI may serve as potential biomarkers or novel therapeutic targets to improve cardiac repair/recovery in diabetic ischemic heart disease.

Chromobacterium violaceum: An incidental finding in a neonate.

Chromobacterium violaceum is a gram-negative saprophytic bacterium causing human infection in tropical and subtropical countries. Such infections are uncommon but cause high mortality when the bacterium enters the bloodstream through an open wound. We present a case of C. violaceum infection isolated from a blood culture sample in a neonate identified at a tertiary care teaching hospital in North East Uttar Pradesh. Timely diagnosis by microbiological methods and antimicrobial treatment led to a successful cure for this life-threatening infection. Thus, such bacteria should be included in the routine spectrum for differential diagnosis of sepsis, to provide a chance of cure.

Mouth Breathing Habit and Their Effects on Dentofacial Growth in Children in the Age Range of 6-14 Years: A Cephalometric Study.

Nasal breathing protects the upper airway and is responsible for adequate craniofacial development. It is believed that long-standing obstruction causes mouth breathing, which has a negative impact on the craniofacial complex. Aim: The study aimed to verify the effects of mouth breathing on the dentofacial structure by employing cephalometric analysis. Materials and methods: The present study was conducted on 68 patients (34 mouth-breathing group or study group and 34 nasal-breathing group or control group) aged 6-14 years. Study subjects were screened based on the inclusion and exclusion criteria. Clinical assessment of nasal function was done to select the mouth breathing patients and referred for ear, nose, and throat (ENT) clearance. Lateral cephalograms were taken for the study subjects, including both nasal and mouth breathers, over which selected landmarks were marked to evaluate linear, skeletal, and dental angular variables for comparison with cephalometric variables of a normal child. Results: The mean values of facial height (N-Me, ANS-Me) and mandibular plane angle (SN-GoGn) were significantly higher for mouth breathers. The gonial angle (Ar-GoMe) for ages 6-14 years was significantly lower in the nasal breathing group. Conclusion: The study led to the conclusion that all subjects with a history of mouth breathing showed an increase in facial height, gonial angle, and mandibular plane angle. Clinical significance: Evaluating dentoskeletal changes in a patient with a mouth-breathing habit helps discern the importance of early identification and interception at an early age, thereby ensuring a functional environment adequate for physiological growth and dentofacial esthetics. How to cite this article: Chowdhary K, Yadav G, Rai A, et al. Mouth Breathing Habit and Their Effects on Dentofacial Growth in Children in the Age Range of 6-14 Years: A Cephalometric Study. Int J Clin Pediatr Dent 2024;17(5):545-551.

A Comparative Evaluation of the Acidogenic Potential of Lactose-based, Soy-based, Protein Hydrolysate-based, and Iron-based Milk Formulas Based on Dental Plaque pH, Salivary pH, and Buffering Capacity: An In Vivo Study.

Aims and background: Breastfeeding is the gold standard nutrition for infants. However, the inability of infants to latch on, maternal complaints of sore or painful nipples, and insufficient milk supply frequently result in early breastfeeding cessation. Hence, milk has subsequently been replaced by infant formula milks of high quality, which serve as an alternate source of nutrition for infants. There also has been a rising concern among parents and caretakers regarding the cariogenic potential of the various milk formulas available in the market due to the presence of fermentable carbohydrates in them, leading to an increase in nursing caries or early childhood caries. Hence, this study aims to comparatively evaluate the acidogenic potential of four different milk formulas based on dental plaque pH, salivary pH, and buffering capacity. Materials and methods: This cross-sectional study was carried out to assess the acidogenic potential of various infant milk formulas using three main parameters of measurement of caries: evaluation of salivary pH, plaque pH, and buffering capacity.Baseline plaque and salivary pH and postconsumption plaque pH and salivary pH were assessed after 5, 10, 15, 20, 30, and 60 minutes in 60 healthy children (15 in each study group) aged 7-12 years after rinsing with group I (lactose-based), group II (soy-based), group III (protein hydrolysate-based), and group IV (iron-based) milk formulas. The pH was assessed using a precalibrated digital pH meter. Plaque pH was also further assessed based on its buffering capacity. Results: Soy-based and protein hydrolysate-based milk formulas were found to be most cariogenic in both saliva and plaque. Lactose-based formulas were found to be the least cariogenic of all the milk formulas. Conclusion: Parents and caretakers must be made aware of the various types of milk formulas available, their composition, as well as their relative cariogenic nature. Feeding should always be supervised, and infants should not be left with milk-containing bottles as comforters. Milk feeds at bedtime, when salivary flow is reduced, should be discouraged. Dentists and pediatricians should be aware of the caries-related risk associated with different milk formulas before recommending them to children. Clinical significance: Knowledge and awareness among parents and caretakers regarding the cariogenicity of various milk formulas available in the market. How to cite this article: Mahanta A, Yadav G, Saha S, et al. A Comparative Evaluation of the Acidogenic Potential of Lactose-based, Soy-based, Protein Hydrolysate-based, and Iron-based Milk Formulas Based on Dental Plaque pH, Salivary pH, and Buffering Capacity: An In Vivo Study. Int J Clin Pediatr Dent 2024;17(8):851-859.

Emergence of rare and uncommon yeast-like pathogens causing neonatal sepsis at a tertiary care center, North India.

Introduction: Neonatal candidemia is a life-threatening event in babies requiring ICU admission. Prompt diagnosis and appropriate treatment reduce mortality and morbidity. Worldwide, there is an emergence of drug-resistant rare Candida species causing neonatal sepsis that necessitates antifungal susceptibility testing in each case. Methods: We did a prospective study to isolate Candida species causing neonatal sepsis and to determine the predisposing risk factors and time to positivity for flagged positivity. We also determined fluconazole, itraconazole and amphotericin B minimum inhibitory concentration (MIC) against isolated Candida species by broth microdilution method using CLSI M27-A3 guidelines. Results: A total of 107 neonatal candidemia events were noted. Prematurity was the most common predisposing risk factor. Most isolates were non-albicans Candida. Candida utilis, C. pelliculosa, C. tropicalis and K. ohmeri were the predominant fungi causing neonatal candidemia. A varied antifungal MIC against isolated Candida species was noted. However, 90% of the isolated Candida strains had <8 µg/mL fluconazole MIC. Moreover, ≥8 and ≥2 µg/mL MIC for fluconazole and amphotericin B respectively were also noted. Conclusions: Rare Candida species having varied fluconazole and amphotericin B MIC cause neonatal candidemia. Therefore, culture isolation and antifungal susceptibility testing should be done in each case of neonatal candidemia.

Role of mitochondrial ribosomal protein L7/L12 (MRPL12) in diabetic ischemic heart disease.

BACKGROUND: Myocardial infarction (MI) is a significant cause of death in diabetic patients. Growing evidence suggests that mitochondrial dysfunction contributes to heart failure in diabetes. However, the molecular mechanisms of mitochondrial dysfunction mediating heart failure in diabetes are still poorly understood. METHODS: We examined MRPL12 levels in right atrial appendage tissues from diabetic patients undergoing coronary artery bypass graft (CABG) surgery. Using AC-16 cells overexpressing MRPL12 under normal and hyperglycemic conditions we performed mitochondrial functional assays OXPHOS, bioenergetics, mitochondrial membrane potential, ATP production and cell death. RESULTS: We observed elevated MRPL12 levels in heart tissue samples from diabetic patients with ischemic heart disease compared to non-diabetic patients. Overexpression of MRPL12 under hyperglycemic conditions did not affect oxidative phosphorylation (OXPHOS) levels, cellular ATP levels, or cardiomyocyte cell death. However, notable impairment in mitochondrial membrane potential (MMP) was observed under hyperglycemic conditions, along with alterations in both basal respiration oxygen consumption rate (OCR) and maximal respiratory capacity OCR. CONCLUSIONS: Overall, our results suggest that MRPL12 may have a compensatory role in the diabetic myocardium with ischemic heart disease, suggesting that MRPL12 may implicate in the pathophysiology of MI in diabetes.

Production and characterization of anti-hypertensive and anti-diabetic peptides from fermented sheep milk with anti-inflammatory activity: in vitro and molecular docking studies.

BACKGROUND: The present study aimed to evaluate the anti-hypertensive and anti-diabetic activities from biologically active peptides produced by fermented sheep milk with Lacticaseibacillus paracasei M11 (MG027695), as well as to purify and characterize the angiotensin-converting enzyme (ACE) inhibitory and anti-diabetic peptides produced from fermented sheep milk. RESULTS: After 48 h of fermentation at 37 °C, sheep milk demonstrated significant changes in anti-diabetic effects and ACE-I effects, with inhibition percentages observed for ACE inhibition (76.32%), α-amylase (70.13%), α-glucosidase (70.11%) and lipase inhibition (68.22%). The highest level of peptides (9.77 mg mL-1) was produced by optimizing the growth conditions, which included an inoculation rate of 2.5% and a 48 h of incubation period. The comparison of molecular weight distributions among protein fractions was conducted through sodium dodecyl-sulfate polyacrylamide gel electrophoresis analysis, whereas spots were separated using 2D gel electrophoresis according to both the molecular weight and pH. Peptide characterization with ultra-filtration membranes at 3 and 10 kDa allowed the study to assess molecular weight-based separation. Nitric oxide generated by lipopolysaccharide and the secretion of pro-inflammatory cytokines in RAW 264.7 immune cells were both inhibited by sheep milk fermented with M11. Fourier-transform infrared spectroscopy was employed to assess changes in functional groups after fermentation, providing insights into the structural changes occurring during fermentation. CONCLUSION: The present study demonstrates that fermentation with L. paracasei (M11) led to significant changes in fermented sheep milk, enhancing its bioactive properties, notably in terms of ACE inhibition and anti-diabetic activities, and the generation of peptides with bioactive properties has potential health benefits. © 2024 Society of Chemical Industry.

Exploring peptidomes of by-products generated during chhurpi production using Lactobacillus delbrueckii WS4 for identification of novel bioactive peptides.

The considerable value of whey is evident from its significant potential applications and contributions to the functional food and nutraceutical market. The by-products were individually obtained during functional chhurpi and novel soy chhurpi cheese production using defined lactic acid bacterial strains of Sikkim Himalaya's traditional chhurpi. Hydrolysis of substrate proteins by starter proteinases resulted in a comparable peptide content in whey and soy whey which was associated with antioxidant and ACE inhibition potential. Peptidome analysis of Lactobacillus delbrueckii WS4 whey and soy whey revealed the presence of several bioactive peptides including the multifunctional peptides PVVVPPFLQPE and YQEPVLGPVRGPFPIIV. In silico analyses predicted the antihypertensive potential of whey and soy whey peptides with strong binding affinity for ACE active sites. QSAR models predicted the highest ACE inhibition potential (IC50) for the ß-casein-derived decapeptide PVRGPFPIIV (0.95 µM) and the Kunitz trypsin inhibitor protein-derived nonapeptide KNKPLVVQF (16.64 µM). Chhurpi whey and soy whey can be explored as a valuable source of diverse and novel bioactive peptides for applications in designer functional foods development.

Biochemical characterization of a novel acid-active endopolygalacturonase for pectin depolymerization, pectic-oligomer production, and fruit juice clarification.

Endopolygalacturonases are crucial pectinases known for their efficient and sustainable pectin depolymerization activities. The present study identified a novel gene encoding endopolygalacturonase from an acidic mine tailing metagenome. The putative gene showed a maximum identity of 67.55 % with an uncharacterized peptide sequence from Flavobacterium fluvii. The gene was cloned and expressed in a heterologous host, E. coli. Biochemical characterization of the novel endopolygalacturonase enzyme variant (EPHM) showed maximum activity at 60 °C and at 5.0 pH, while retaining 50 % activity under the temperature and pH range of 20 °C to 70 °C for 6 h, and 3.0 to 10.0 for 3 h, respectively. The enzyme exhibited tolerance to different metal ions. EPHM was characterized for the depolymerization of methylated pectin into pectic oligosaccharides. Further, its utility was established for fruit juice clarification, as endorsed by high transmittance, significant viscosity reduction, and release of reducing sugars in the treated fruit juice samples.

Potential of fermented foods and their metabolites in improving gut microbiota function and lowering gastrointestinal inflammation.

Foods prepared using microbial conversion of major and minor food components, which are otherwise known as fermented foods continue to impact human health. The live microorganisms and transformed metabolites can also have a deep influence on the gut microbiota, the multifaceted population of microorganisms dwelling inside the gut play a key role in wellbeing of an individual. The probiotic strains delivered through the consumption of fermented food and other bioactive components such as polyphenolic metabolites, bioactive peptides, short-chain fatty acids and others including those produced via gut microbiota mediated transformations have been proposed to balance the gut microbiota diversity and activity, and also to regulate the inflammation in the gut. However, little is known about such effects and only a handful of fermented foods have been explored to date. We herein review the recent knowledge on the dysbiotic gut microbiota linking to major gut inflammatory diseases. Also, evidences that fermented food consumption modulates the gut microbiota, and its impact on the gut inflammation and inflammatory diseases have been discussed. © 2024 Society of Chemical Industry.

The way forward to produce nutraceuticals from agri-food processing residues: obstacle, solution, and possibility.

Food matrices contain bioactive compounds that have health benefits beyond nutritional value. The bulk of bioactive chemicals are still present in agro-industrial by-products as food matrices. Throughout the food production chain, there is a lot of agro-industrial waste that, if not managed effectively, could harm the environment, company, and how nutritiously and adequately people eat. It's important to establish processes that maximise the use of agro-industrial by-products, such as biological technologies that improve the extraction and acquisition of bioactive compounds for the food and pharmaceutical industries. As opposed to nonbiological processes, biological procedures provide high-quality, bioactive extracts with minimum toxicity and environmental impact. Fermentation and enzymatic treatment are biological processes for obtaining bioactive compounds from agro-industrial waste. In this context, this article summarises the principal bioactive components in agro-industrial byproducts and the biological methods employed to extract them. In this review efficient utilization of bioactive compounds from agro-industrial waste more effectively in food and pharmaceutical industries has been described.

A contemporary review of snoRNAs in cardiovascular health: RNA modification and beyond.

As cardiovascular diseases continue to be the leading cause of death worldwide, groundbreaking research is being conducted to mitigate their effects. This review looks into the potential of small nucleolar RNAs (snoRNAs) and the opportunity to use these molecular agents as therapeutic biomarkers for cardiovascular issues specific to the heart. Through an investigation of snoRNA biogenesis, functionality, and roles in cardiovascular diseases, this review relates our past and present knowledge of snoRNAs to the current scientific literature. Considering the initial discovery of snoRNAs and the studies thereafter analyzing the roles of snoRNAs in disease, we look forward to uncovering many other noncanonical functions that could lead researchers closer to finding preventive and curative solutions for cardiovascular diseases.

Production of mulberry wine using selenium-enriched Saccharomyces cerevisiae: implications from sensory analysis, phytochemical and antioxidant activities.

The present study aims to evaluate the quality of chemical, sensory properties and antioxidant potential of mulberry wine using selenium-enriched yeasts employing eight different methods (MW1-MW8). The selenium-enriched yeast significantly (p < 0.05) increased phytochemical profiles, flavor, quality and antioxidant capacity. The most effective method for raising the selenium level of mulberry wine was using L-seMC (MW5). Mulberry wine color was attributed to the anthocyanins and phytochemical composition with selenium content. DPPH and ABTS radical scavenging activity varied with change in treatment methods suggesting their impact on antioxidant activity. Total selenium content on L-SeMC supplementation proved a significant correlation between selenium content with total anthocyanin content, total polyphenol content and flavonoid content. Sensory analysis by electronic nose exhibited MW2 with high response value in the W2S sensor showing high alcohol concentration. GC-MS analysis showed the presence of 57 volatile aromatic compounds comprehended by esters and alcohol (isoamyl alcohol, 2-methylbutanol, 2,3-butanediol, and phenethyl alcohol). Principal component analysis affirms the response values for four categorical score values with reliability and consistency for all the parameters, significantly. Thus, the workflow demonstrates a simpler, cost-effective traditional methodology for rationalized outcomes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05847-4.

Lifetime evaluation of left ventricular structure and function in male ApoE null mice after gamma and space-type radiation exposure.

The space radiation (IR) environment contains high charge and energy (HZE) nuclei emitted from galactic cosmic rays with the ability to overcome current shielding strategies, posing increased IR-induced cardiovascular disease risks for astronauts on prolonged space missions. Little is known about the effect of 5-ion simplified galactic cosmic ray simulation (simGCRsim) exposure on left ventricular (LV) function. Three-month-old, age-matched male Apolipoprotein E (ApoE) null mice were irradiated with 137Cs gamma (γ; 100, 200, and 400 cGy) and simGCRsim (50, 100, 150 cGy all at 500 MeV/nucleon (n)). LV function was assessed using transthoracic echocardiography at early/acute (14 and 28 days) and late/degenerative (365, 440, and 660 days) times post-irradiation. As early as 14 and 28-days post IR, LV systolic function was reduced in both IR groups across all doses. At 14 days post-IR, 150 cGy simGCRsim-IR mice had decreased diastolic wall strain (DWS), suggesting increased myocardial stiffness. This was also observed later in 100 cGy γ-IR mice at 28 days. At later stages, a significant decrease in LV systolic function was observed in the 400 cGy γ-IR mice. Otherwise, there was no difference in the LV systolic function or structure at the remaining time points across the IR groups. We evaluated the expression of genes involved in hemodynamic stress, cardiac remodeling, inflammation, and calcium handling in LVs harvested 28 days post-IR. At 28 days post-IR, there is increased expression of Bnp and Ncx in both IR groups at the lowest doses, suggesting impaired function contributes to hemodynamic stress and altered calcium handling. The expression of Gals3 and ß-Mhc were increased in simGCRsim and γ-IR mice respectively, suggesting there may be IR-specific cardiac remodeling. IR groups were modeled to calculate the Relative Biological Effectiveness (RBE) and Radiation Effects Ratio (RER). No lower threshold was determined using the observed dose-response curves. These findings do not exclude the possibility of the existence of a lower IR threshold or the presence of IR-induced cardiovascular disease (CVD) when combined with additional space travel stressors, e.g., microgravity.

Molecular binding mechanism and novel antidiabetic and anti-hypertensive bioactive peptides from fermented camel milk with anti-inflammatory activity in raw macrophages cell lines.

The investigation was to determine the effect of camel milk fermented with Limosilactobacillus fermentum KGL4 (MTCC 25515) on ACE-inhibiting, anti-inflammatory, and diabetes-preventing properties and also to release the novel peptides with antidiabetic and anti-hypertensive attributes with molecular interaction studies. Growth conditions were optimised on the basis of total peptide production by inoculating the culture in camel milk at different rates (1.5, 2.0, and 2.5%) along with different incubation periods (12, 24, 36, and 48 h). However, after 48 h of fermentation with a 2.5% rate of inoculum, the highest proteolytic activity was obtained. Reverse phase high-pressure liquid chromatography (RP-HPLC) was used to calculate the % Rpa from permeates of 3 kDa and 10 kDa fractions. Molecular weight distributions of fermented and unfermented camel milk protein fractions were compared using SDS-PAGE. Spots obtained from 2D gel electrophoresis were separated on the basis of pH and molecular weight. Spots obtained from 2D gel were digested with trypsin, and the digested samples were subjected to RP-LC/MS for the generation of peptide sequences. The inhibition of tumour necrosis factor alpha, interleukin-6, and interleukin-1 during fermentation was studied using RAW 264.7 macrophages. In the study, fermented camel milk with KGL4 (CMKGL4) inhibited LPS-induced nitric oxide (NO) production and pro-inflammatory cytokine production (TNF-α, IL-6, and IL-1ß) by the murine macrophages. The results showed that the peptide structures (YLEELHRLNK and YLQELYPHSSLKVRPILK) exhibited considerable binding affinity against hPAM and hMGA during molecular interaction studies.

Lactic acid bacteria in the functional food industry: biotechnological properties and potential applications.

With the growing demand for functional foods having better nutraceutical properties, lactic acid bacteria (LAB) has become an important industrial microorganism. LAB play a significant role in the functional food industry by exhibiting probiotic properties and has the ability to produce various biologically active metabolites such as γ-aminobutyric acid (GABA), exopolysaccharides (EPSs), conjugated linoleic acid (CLA), bacteriocins, reuterin and reutericyclin, which provides enhanced nutraceutical properties to the final food products. LAB are also known to produce several specific enzymes essential for producing substrate-derived bioactive compounds, such as polyphenols, bioactive peptides, inulin-type fructans and ß-glucans, fatty acids, and polyols. These compounds exhibit many health benefits, including better mineral absorption, oxidative stress protection, blood glucose and cholesterol-lowering properties, prevention of gastrointestinal tract infections and improved cardiovascular function. Further, metabolically engineered LAB have been widely used for the nutritive enhancement of different food products and the application of CRISPR-Cas9 holds tremendous potential for the engineering of food cultures. This review provides an overview of the use of LAB as probiotics, its application in producing fermented foods and nutraceutical products, and its health benefits on the host.

Structural Characteristics, Physicochemical Properties, and Digestibility Analysis of Resistant Starch Type-V Prepared from Debranched Corn Starch and Fatty Acid Complexation.

Corn starch was gelatinized and treated with a metagenomic type 1 pullulanase (PulM), increasing the proportion of linear glucan chains. The debranched corn starch (DCS), containing amylose helices, was subjected to complexation with fatty acid molecules at moderate temperatures (50-60 °C). The amylose-lipid complexes prepared using saturated fatty acids, e.g., capric acid (CA) and lauric acid (LA), displayed higher CI values as compared to that of unsaturated fatty acid compounds, e.g., undecylenic acids (UAs) and oleic acid (OA). The DCS-fatty acid complex was estimated to contain about 14% of rapidly digested starch (RDS), 26% of slowly digested starch (SDS), and 60% of resistant starch V (RS-5). RS-5 samples exhibited high resistance toward digestive enzymatic hydrolysis. The surface microdetails of RS-5 were examined by scanning electron microscopy (SEM), depicting small spherulite-like structural aggregates. X-ray diffraction pattern analysis estimated about 46% of the crystallinity of RS-5. Thermal attributes of RS-5 were examined by thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) analysis, depicting the increase in melting enthalpies after the complexation of fatty acid molecules with debranched corn starch. Comparative DSC thermograms divulged a relatively higher stability of RS-5 as compared to that of RS-3. The findings advocated the potentiality of RS-5 (nondigestible DCS-LA complex) as a functional, valuable ingredient in the food industry.