BACKGROUND: A major issue is finding a valid biomarker able to diagnose periodontal disease with the presence and absence of risk factors. Indeed, the association between smoking and periodontal diseases and its impact on the manifestation of antimicrobial peptides has been delineated in clinical and epidemiological investigations. The antimicrobial peptide cathelicidin (LL-37) is pivotal in preserving periodontal health. OBJECTIVES: This investigation examines and contrasts the levels of cathelicidin in the saliva of smokers and nonsmokers of periodontitis. The study also seeks to establish this biomarker's diagnostic ability to differentiate between periodontal health and disease. MATERIALS AND METHODS: The study involved the collection of unstimulated saliva samples from 160 participants, comprising 80 patients diagnosed with periodontitis (40 of whom were smokers and 40 were nonsmokers) and 80 periodontitis-free individuals (40 smokers and 40 nonsmokers). The clinical periodontal parameters were assessed, including recording the probing pocket depth, the level of clinical attachment, and the percentage of bleeding on probing. Subsequently, enzyme-linked immunosorbent assays were conducted to quantify the protein levels of LL-37 in the saliva samples obtained from the subjects mentioned above. RESULTS: The highest level of salivary LL-37 was found in the nonsmoker periodontitis (NSP) patients, followed by the group of smoker periodontitis (SP) and then nonsmoker healthy (NSH) group, while the lowest level was found in the healthy smoker (HS) group. At the same time, the LL-37 seems to be a very good biomarker in differentiating periodontal health from disease with the presence and absence of smoking. CONCLUSION: Periodontitis results in a significant elevation of salivary LL-37 levels in smoker and nonsmoker patients compared to healthy individuals. These levels are positively correlated with the periodontal parameter and can serve as a valuable diagnostic tool to predict periodontitis, whereas smoking significantly reduces these levels.

BACKGROUND: Recent researches have failed to uncover a clear explanation for proton pump inhibitors' bone-loss effects. In light of pantoprazole's effects on gastrin secretion, the goal of this study was to see if it caused bone loss through gastrin secretion. METHODS: Forty male rats were divided into control, octreotide (Oct), pantoprazole (Pan), and pantoprazole plus octreotide (Pan+Oct) groups. Serum calcium, phosphorous, alkaline phosphatase, parathyroid hormone, and gastrin were measured before and three months after the treatment, and bone densitometry was examined. The rats' femoral bones were examined stereologically at the end of the investigation. RESULTS: The Pan group had considerably greater levels of serum alkaline phosphatase, parathyroid hormone (PTH), and gastrin, but this was prevented in the presence of Oct, a gastrin secretion inhibitor. All parameters of femoral bone densitometry in the Pan group were significantly lower than the control after treatment which was considerably inhibited in the presence of Oct. Furthermore, when compared to the control and Oct groups, the rats in the Pan group had a lower trabecular volume, femur bone weight, and volume, as well lower number of osteocytes. The amount of osteoclasts, on the other hand, was much higher in the Pan group than in the other groups. CONCLUSION: Overall findings revealed that pantoprazole caused bone loss, which could be prevented by adding octreotide. Because these detrimental effects were not detected in rats given both Oct and Pan, it was suggested that the effect of Pan on bone was produced by a hypergastrinemic condition.

Leishmania parasites, which are spread by infected female sand flies, are the cause of the disease leishmaniasis. Although cutaneous leishmaniasis has been found to occur in the Volta Region, there is limited data on vector species and reservoirs. This study focused on the Tsatee community, in the South Dayi District of the Volta Region, and is aimed at identifying the sand fly fauna and detecting the presence of Leishmania DNA by the use of primers that target the conserved region of Leishmania spp. minicircle DNA of the parasite kinetoplast. The miniature light traps and hand aspirators provided by the Centers for Disease Control and Prevention (CDC) were used to collect outdoor and indoor sand flies for five months in a guinea woodland and semideciduous forest area. From the collections, 4,580 phlebotomine sand flies were obtained and identified, and females were examined for Leishmania DNA using PCR. The male flies were 1,202 (26.24%), non-blood-fed females were 3,321 (72.51%), and 57 (1.25%) were blood-fed females. It was observed that Sergentomyia species constituted 99.91% of the total collected sand flies with S. africana (76.77%) as the predominant species. Phlebotomus rodhaini (0.09%) was the only Phlebotomus species identified from the study area. From 283 non-blood-fed sand fly pools and 57 individual blood-fed species screened, Leishmania DNA was detected in 12 (4.24%) pools and 8 (14.04%) individuals, respectively. It was observed that Leishmania DNA was detected in all the sand fly species identified except S. collarti. This study reports the first detection of Leishmania DNA in P. rodhaini in Ghana, with an infection rate of 33.33% (95% CI, 1.23-88.32). The findings suggest that the role of Phlebotomus in disease transmission in the study area cannot be discounted. Future studies should include continuous surveillance, blood meal preferences, and vector competence of the various infected phlebotomine sand flies to create effective control measures.

BACKGROUND: The resistance to antibiotics shown by some dermatological pathogenic microorganisms has increased the interest of pharmaceutical and cosmetic industries in developing natural products that possess different biological activities, including antimicrobial effects. METHODS: In the present investigation, the antibacterial activity of ethanolic extracts of Dodonaea viscosa aerial part and Mammea americana leaves and seed was evaluated against resistant strains of Staphylococcus isolated from skin lesions and against S. aureus ATCC 25923 (reference strain). Column chromatography (CC) and preparative thin-layer chromatography (PTLC) were used to obtain separate fractions of the seed extract of M. americana. We also determined the antimicrobial resistance of the strains against antibiotics using the agar disc diffusion assay. In addition, phytochemical screening was performed by colorimetric standard techniques. RESULTS: M. americana seed extract showed the highest antibacterial activity with MBC from 2.3 μg/mL to 19.5 μg/mL without differences with gentamicin (p = 0.998). The isolated strain S. epidermidis I showed the highest antimicrobial resistance against the tested antibiotics. PTLC-fractions of M. americana seed extract showed MBC from 3.2 μg/mL to 40.7 μg/mL against S. epidermidis I and S. aureus 25923 (reference), respectively, which suggests a synergistic effect of the secondary metabolites present in the crude ethanolic extract compared to its active PTLC-fractions, where only coumarins and compounds with lactone groups were detected in the phytochemical screening. CONCLUSION: M. americana seed extract has promising effects that should be considered in further studies as an alternative or adjuvant in treating skin infections caused by staphylococci.

Infectious diseases have been tremendously increasing as the organisms of even normal flora become opportunistic and cause an infection, and Escherichia coli (E. coli EQ101) is one of them. Urinary tract infections are caused by various microorganisms, but Escherichia coli is the primary cause of almost 70%-90% of all UTIs. It has multiple strains, possessing diverse virulence factors, contributing to its pathogenicity. Furthermore, these virulent strains also can cause overlapping pathogenesis by sharing resistance and virulence factors among each other. The current study is aimed at analyzing the genetic variants associated with multi-drug-resistant (MDR) E. coli using the whole genome sequencing platform. The study includes 100 uropathogenic Escherichia coli (UPEC) microorganisms obtained from urine samples out of which 44% were multi-drug-resistant (MDR) E. coli. Bacteria have been isolated and antimicrobial susceptibility test (AST) was determined by disk diffusion method on the Mueller-Hinton agar plate as recommended by the Clinical and Laboratory Standards Institute (CLSI) 2020, and one isolate has been selected which shows resistance to most of the antibiotics, and that isolate has been analyzed by whole genome sequencing (WGS), accompanied by data and phylogenetic analysis, respectively. Organisms were showing resistance against ampicillin (10 μg), cefixime (5 μg), ceftriaxone (30 μg), nalidixic acid (30 μg), ciprofloxacin (5 μg), and ofloxacin (5 μg) on antimicrobial susceptibility test. WGS were done on selected isolate which identified 25 virulence genes (air, astA, chuA, fyuA, gad, hra, iha, irp2, iss, iucC, iutA, kpsE, kpsMII_K1, lpfA, mchF, ompT, papA_F43, sat, senB, sitA, terC, traT, usp, vat, and yfcV) and seven housekeeping genes (adk, fumC, gyrB, icd, mdh, purA, and recA). Among resistance genes, seven genes (TolC, emrR, evgA, qacEdelta1, H-NS, cpxA, and mdtM) were identified to be involved in antibiotic efflux, three AMR genes (aadA5, mphA, and CTX-M-15) were involved in antibiotic inactivation, and two genes (sul1 and dfrA14) were found to be involved in antibiotic drug replacement. Our data identified antibiotic resistance and virulence genes of the isolate. We suggest further research work to establish region-based resistance profile in comparison with the global resistance pattern.

BACKGROUND: Advances in cancer research have allowed for early diagnosis and improved treatment of cutaneous melanoma (CM). However, its invasiveness and recurrent metastasis, along with rising resistance to newer therapies, have lent urgency to the search for novel biomarkers and the underlying molecular mechanisms of CM. METHODS: Single nucleotide polymorphism- (SNP-) related genes were obtained from the sequencing data of 428 CM samples in The Cancer Genome Atlas. Functional enrichment of these genes was analysed in clusterProfiler. Additionally, a protein-protein interaction (PPI) network was constructed with the Search Tool for the Retrieval of Interacting Gene (STRING) database. Gene Expression Profiling Interactive Analysis (GEPIA) was used to identify the expression and prognostic value of mutated genes. Finally, the Tumour Immune Estimation Resource (TIMER) analysed the relationship between gene expression and immune cell infiltration. RESULTS: We constructed a PPI network from the top 60 SNP-related genes. Mutated genes were mainly involved in calcium and oxytocin signalling pathways, as well as circadian entrainment. In addition, three SNP-related genes, BRAF, FLG, and SORL1, were significantly associated with patient prognosis. BRAF and SORL1 were positively associated with infiltration abundance of B cells, CD8+ T cells, CD4+ T cells, neutrophils, and dendritic cells, whereas FLG expression was negatively associated. Furthermore, higher immune cell infiltration was positively correlated with good prognosis. CONCLUSIONS: Our study provides vital bioinformatic data and a relevant theoretical basis to further explore the molecular pathogenesis of CM and improve patient prognosis.

The hepatitis B virus (HBV) is one of the major viral infection problems worldwide in public health. The exclusive proprietary Chinese medicine Ganweikang (GWK) tablet has been marketed for years in the treatment of chronic hepatitis B (CHB). However, the pharmacodynamic material basis and underlying mechanism of GWK are not completely clear. This study is aimed at investigating the pharmacological mechanism of the GWK tablet in the treatment of CHB. The chemical ingredient information was obtained from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP), Traditional Chinese Medicines Integrated Database (TCMID), and Shanghai Institute of Organic Chemistry of CAS. Ingredients and disease-related targets were defined by a combination of differentially expressed genes from CHB transcriptome data and open-source databases. Target-pathway-target (TPT) network analysis, molecular docking, and chemical composition analysis were adopted to further verify the key targets and corresponding active ingredients of GWK. Eight herbs of GWK were correlated to 330 compounds with positive oral bioavailability, and 199 correlated targets were identified. The TPT network was constructed based on the 146 enriched targets by KEGG pathway analysis, significantly associated with 95 pathways. Twenty-five nonvolatile components and 25 volatile components in GWK were identified in UPLC-QTOF/MS and GC-MS chromatograms. The key active ingredients of GWK include ferulic acid, oleanolic acid, ursolic acid, tormentic acid, 11-deoxyglycyrrhetic acid, dibenzoyl methane, anisaldehyde, wogonin, protocatechuic acid, psoralen, caffeate, dimethylcaffeic acid, vanillin, β-amyrenyl acetate, formonentin, aristololactam IIIa, and 7-methoxy-2-methyl isoflavone, associated with targets CA2, NFKB1, RELA, AKT1, JUN, CA1, CA6, IKBKG, FOS, EP300, CREB1, STAT1, MMP9, CDK2, ABCB1, and ABCG2.

Considering the unique properties of magnesium and its alloy, it has a vast demand in biomedical applications, particularly the implant material in tissue engineering due to its biodegradability. But the fixing spares must hold such implants till the end of the biodegradation of implant material. The composite technology will offer the added benefits of altering the material properties to match the requirements of the desired applications. Hence, this experimental investigation is aimed at developing a composite material for manufacturing fixing spares like a screw for implants in biomedical applications. The matrix of AZ63 magnesium alloy is reinforced with nanoparticles of zirconium (Zr) and titanium (Ti) through the stir casting-type synthesis method. The samples were prepared with equal contributions of zirconium (Zr) and titanium (Ti) nanoparticles in the total reinforcement percentage (3%, 6%, 9%, and 12%). The corrosive and tribological studies were done. In the corrosive study, the process parameters like NaCl concentration, pH value, and exposure time were varied at three levels. In the wear study, the applied Load, speed of sliding, and the distance of the slide were considered at four levels. Taguchi analysis was employed in this investigation to optimize the reinforcement and independent factors to minimize the wear and corrosive losses. The minimum wear rate was achieved in the 12% reinforced sample with the input factor levels of 60 N of load on the pin, 1 m/s of disc speed at a sliding distance was 1500 m, and the 12% reinforce samples also recorded a minimum corrosive rate of 0.0076 mm/year at the operating environment of 5% NaCl-concentrated solution with the pH value of 9 for 24 hrs of exposure. The prediction model was developed based on the experimental results.

The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.

Mosquitoes present an immense threat to millions of people worldwide and act as vectors for filariasis disease. The objective of the study was to determine the effect of Allium sativum and Zingiber officinale extracts against filariasis vectors. The larvae were collected from the breeding site by using standard procedures for identification and larvicidal activities. Twenty grams (20 g) from each (Allium sativum and Zingiber officinale) were extracted separately by aqueous, ethanol, and methanol solvents. The phytochemical analysis was determined in the crude sample by using standard methods. Then, larvicidal effects were determined by introducing 10 larvae of the vectors to the concentrations of 250 ppm, 500 ppm, and 750 ppm of the crude sample, and data were subjected to probit analysis to determine the LC50 and Chi-squared test to check the significance of the mortality by R software. Anopheles funestus, Anopheles gambiae s.l., Anopheles pharoensis, Culex antennatus, and Culex quinquefasciatus were the filariasis vectors identified during the study period. The presence of phytochemical tests such as anthraquinones, flavonoids, glycosides, phenol, saponin, steroids, tannin, and terpenes was obtained. The larvicidal effects of the selected plant extracts ranged from 0%-100%. The lowest LC50 (53 ppm) was observed for A. sativum methanol test extract against Cx. quinquefasciatus. Ethanol extracts of A. sativum have a significant effect on An. funestus (X2 = 7.5, p = 0.02352) and Cx. quinquefasciatus (X2 = 10.833, p = 0.0.0044), whereas aqueous extracts have a significant effect only on An. gambiae s.l. (X2 = 7.0807, p = 0.029. Ethanol extracts of Z. officinale have a significant effect only on the mortality of An. pharoensis (X2 = 7.0807, p = 0.029), but methanol and aqueous extracts have no significant effect against filariasis vectors. In conclusion, A. sativum have a high toxic effect than Z. officinale extract against filariasis vectors in all type of solvents. So using those plant extracts is the best to reduce the risk of the synthetic chemical on nontarget organisms and the environment, in addition to the control of mosquito-borne diseases, but further studies will be conducted to evaluate the toxicity at different stages of the vectors.

BACKGROUND: Nowadays, due to various inherent properties, graphene-based nanoparticles are widely used in drug delivery research. On the other hand, folate receptors are highly expressed on the surface of human tumor cells. In this work, to enhance the 5-fluorouracil (5FU) and curcumin (Cur) effects on colon cancer, we constructed a folic acid- (FA-) modified codelivery carrier based on graphene nanoparticles (GO-Alb-Cur-FA-5FU). MATERIALS AND METHODS: The HUVEC and HT-29 were selected for evaluating the antitumor effect of the prepared nanocarriers. The structure of nanocarriers was characterized by FTIR spectroscopy, X-ray diffraction analysis, TEM microscopy, and a DLS analyzer. The efficiency of the prepared carrier was evaluated by fluorescence microscopy using Annexin V and the PI kit. The cytotoxicity of the carrier's component individually and the efficacy of the drug carrier GO-Alb-Cur-FA-5FU were assessed by MTT. RESULTS: The results of the pharmacological tests indicated that the new nanoparticles cause increased apparent toxicity in HT-29 cells. The apoptosis rate of the HT-29 and HUVEC cells treated with IC50 values of GO-Alb-Cur-FA-5FU for 48 h was higher than the cells treated with IC50 values of 5FU and Cur individually, which indicated the greater inhibitory efficacy of GO-Alb-Cur-FA-5FU than free drugs. CONCLUSION: The designed GO-Alb-CUR-FA-5FU delivery system can be applied for targeting colon cancer cells and can be severe as a potential candidate for future drug development.

The Sahara Desert, one of the most extreme ecosystems in the planet, constitutes an unexplored source of microorganisms such as mycelial bacteria. In this study, we investigated the diversity of halophilic actinobacteria in soils collected from five regions of the Algerian Sahara. A total of 23 halophilic actinobacterial strains were isolated by using a humic-vitamin agar medium supplemented with 10% NaCl. The isolated halophilic strains were subjected to taxonomic analysis using a polyphasic approach, which included morphological, chemotaxonomic, physiological (numerical taxonomy), and phylogenetic analyses. The isolates showed abundant growth in CMA (complex medium agar) and TSA (tryptic soy agar) media containing 10% NaCl, and chemotaxonomic characteristics were consistent with their assignment to the genus Nocardiopsis. Analysis of the 16S rRNA sequence of 23 isolates showed five distinct clusters and a similarity level ranging between 98.4% and 99.8% within the Nocardiopsis species. Comparison of their physiological characteristics with the nearest species showed significant differences with the closely related species. Halophilic Nocardiopsis isolated from Algerian Sahara soil represents a distinct phyletic line suggesting a potential new species. Furthermore, the isolated strains of halophilic Nocardiopsis were screened for their antagonistic properties against a broad spectrum of microorganisms by the conventional agar method (agar cylinders method) and found to have the capacity to produce bioactive secondary metabolites. Except one isolate (AH37), all isolated Nocardiopsis showed moderate to high biological activities against Pseudomonas syringae and Salmonella enterica, and some isolates showed activities against Agrobacterium tumefaciens, Serratia marcescens, and Klebsiella pneumoniae. However, no isolates were active against Bacillus subtilis, Aspergillus flavus, or Aspergillus niger. The obtained finding implies that the unexplored extreme environments such as the Sahara contain many new bacterial species as a novel drug source for medical and industrial applications.

In Cameroon, malaria is still the cause of several deaths yearly and leading to the continued search for new potent leads to fight against Plasmodium falciparum. Medicinal plants like Hypericum lanceolatum Lam. are introduced in local preparations for the treatment of affected people. The bioassay-guided fractionation of the crude extract of the twigs and stem bark of H. lanceolatum Lam. led to the identification of the dichloromethane-soluble fraction as the most active (with 32.6% of the parasite P. falciparum 3D7 survival) which was further purified by successive column chromatography to obtain four compounds identified by their spectrometric data as two xanthones 1,6-dihydroxyxanthone (1) and norathyriol (2) and two triterpenes betulinic acid (3) and ursolic acid (4). In the antiplasmodial assay against P. falciparum 3D7, the triterpenoids 3 and 4 displayed the most significant potencies with IC50 values of 2.8 ± 0.8 μg/mL and 11.8 ± 3.2 μg/mL, respectively. Furthermore, both compounds were also the most cytotoxic against P388 cell lines with IC50 values of 6.8 ± 2.2 μg/mL and 2.5 ± 0.6 μg/mL, respectively. Further insights on the inhibition method of the bioactive compounds and their drug-likeness were obtained from their molecular docking and ADMET studies. The results obtained help in identifying additional antiplasmodial agents from H. lanceolatum and support its use in folk medicine for the treatment of malaria. The plant might be considered as a promising source of new antiplasmodial candidates in new drug discovery.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by dementia as the primary clinical symptom. The production and accumulation of aggregated β-amyloid (Aβ) in patient brain tissues is one of the hallmarks of AD pathogenesis. Microglia, brain-resident macrophages, produce inflammatory cytokines in response to Aβ oligomers or fibrils exacerbating Aβ pathology in AD. HMO6 cells were treated with Aβ42 in the presence or absence of 1,25-dihydroxy vitamin D3 (1,25(OH)2D3) to determine its potential immunomodulatory effects, and the expression of pro-/anti-inflammatory cytokines, M1/M2-associated markers, Toll-like receptors (TLRs), and triggering receptor expressed on myeloid cells 2 (TREM2) was examined. 1,25(OH)2D3 was found to suppress Aβ-induced expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6), M1 markers (CD86 and iNOS), and TLR2/4, whilst increasing the expression of anti-inflammatory cytokines (IL-4, IL-10, and CCL17) and M2 markers (CD206 and Arg-1). Furthermore, 1,25(OH)2D3 promoted TREM2 expression and Aβ uptake by HMO6 cells, and the enhancement of Aβ uptake and M2 polarization was revealed to be TREM2-dependent. The findings of this study suggest that 1,25(OH)2D3 facilitates M2 polarization and Aβ uptake in a TREM2-dependent manner.

Pathophysiologically, type 2 diabetes can result from insulin resistance or insulin insufficiency alone. It is unclear whether relative insulin shortage or pronounced insulin resistance is linked to poor cardiometabolic problems like obesity. Therefore, the objective of this study was to evaluate the relationship between insulin resistance (IR), hypertension, and dyslipidaemia, in men with type 2 diabetes mellitus. One hundred and twenty-one (121) type 2 diabetic men participated in this cross-sectional study, which was conducted between September 2018 and September 2019. Sociodemographic information was collected using a self-designed questionnaire. Anthropometric data were also taken and blood samples collected for estimation of insulin, glucose, and lipid concentrations. HOMA-IR was calculated from the fasting insulin and glucose values, and a HOMA - IR ≥ 2 was considered to indicate insulin resistance. Of the 121 participants, 39.7% were classified as insulin-resistant. Levels of total cholesterol (4.82 ± 1.2 mmol/L; p = 0.007 vs. 4.25 ± 1.1 mmol/L), LDL cholesterol (3.17 ± 0.9 mmol/L; p = 0.001 vs. 2.52 ± 0.8 mmol/L), and TC/HDL-C ratio (3.93 ± 0.9; p = 0.042 vs. 3.58 ± 0.9) and the prevalence of abnormal LDL-C (14.6%; p = 0.015 vs. 2.7%) and elevated BP (83.3%; p = 0.048 vs. 67.1%) were higher in the insulin-resistant group. LDL cholesterol (AUC = 0.670; p = 0.001) better classified subjects as being insulin-resistant compared to other lipid markers. The odds of insulin resistance in dyslipidaemia were not statistically significant after adjusting for obesity. The link between insulin resistance and dyslipidaemia and hypertension in male diabetics may thus be mediated by obesity.

BACKGROUND: The multiple forms of malnutrition, including overnutrition, undernutrition, and diet-related noncommunicable diseases, are emerging crises in Asian countries. Past studies have focused more on malnutrition among overweight/obese individuals; however, limited research has examined chronic energy-deficient adults. Therefore, this study is aimed at investigating the prevalence and determinants of different forms of malnutrition among adults with different body mass index, using the Philippines as an example. Findings from this study will guide the development and implementation of public health nutrition programs and policies. METHODS: A representative dataset from the 2013 Philippine National Nutrition Survey was used in the study. Adults aged ≥20 years (n = 16,826) were included in the analysis after excluding those with missing values. Six phenotypes of malnutrition were assessed, including three in overweight/obese adults (overweight/obese with metabolic syndrome; those with micronutrient deficiency-anemia, vitamin A deficiency, and iodine insufficiency; and those with both metabolic syndrome and micronutrient deficiency) and three in chronic energy-deficient (CED) adults (CED with either metabolic syndrome or micronutrient deficiency and with both metabolic syndrome and micronutrient deficiency). Sociodemographic and lifestyle factors were examined as the determinants of different forms of malnutrition, and multinomial logistic regression analyses were performed. RESULTS: The prevalence of the six phenotypes of malnutrition ranged from 0.4% to 10.2%, where overweight/obese with metabolic syndrome was the most predominant type. The multinomial logistic regression models indicated that older age was the major risk factor across all phenotypes. Sex was associated with the outcomes in the overweight/obesity group, whereas employment status was correlated with CED adults. Furthermore, higher educational levels, being married, living in affluent households, and not smoking were protective factors for conditions related to CED but not overweight/obese individuals. CONCLUSION: Malnutrition in all its forms is a significant public health concern that must be understood and addressed. Policymakers should implement appropriate intervention programs to control these nutritional problems considering the specific risk factors for the adult population.

BACKGROUND: In the present work, we investigated the effect of exogenous glutathione in old rats on the expression of ATP-sensitive potassium (KATP) channels, the mitochondrial permeability transition pore (mPTP) opening in the heart, and the vasorelaxation responses of isolated aortic rings to activation of KATP channels. METHODS: Experiments were performed on adult (6 months) and old (24 months) male Wistar rats, which were divided into three groups: adult, old, and glutathione-treated old rats. Glutathione was injected intraperitoneally at a dose of 52 mg/kg 1 hour before the studies. The mRNA expression of KATP channels was determined using reverse transcription and real-time polymerase chain reaction analysis. The effect of glutathione administration on mPTP opening, relaxation responses of isolated aortic rings, and oxidative stress markers was studied. RESULTS: It was shown that the expression levels of Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and levels of reduced glutathione were significantly increased in glutathione-treated old rats (by 8.3, 2.8, 13.1, and 1.5-fold, respectively), whereas the levels of oxidative stress markers (hydrogen peroxide, diene conjugates, malondialdehyde, and rate of superoxide generation) in heart mitochondria and mPTP opening were significantly reduced. Relaxation of aortic rings was significantly increased in response to the actions of KATP channel openers flocalin and pinacidil in glutathione-treated animals, which was prevented by glibenclamide. CONCLUSIONS: Thus, the administration of exogenous glutathione to old rats resulted in a significant increase in the expression levels of the Kir6.1, Kir6.2, and SUR1 subunits of KATP channels and a decrease in oxidative stress. This was accompanied by inhibition of mPTP opening and enhancement of vasorelaxation responses to activation of KATP channels.

Lactoferrin (LF) is a major natural antimicrobial agent secreted in body fluids as a natural innate immunity protein. The action and structure of LF are closely related to its iron-binding capacity with structural reporting in open and closed conformations. This study looked at how lactoferrin structures change in camel (cLF), bovine (bLF), and human (hLF) lactoferrin closed forms after iron is removed from their binding sites. Initially, the sequence comparison between cLF and the LFs of marine mammals, bats, and domestic animals was the most intriguing conclusion. Camel LF is revealed to be more closely related to marine animals (~80.36% identity) and bats (~79.3% identity) than to terrestrial mammal species (~75.5% identity). Results indicated that cLF was more dynamic in nature than bLF and hLF by showing higher RMSD values. The cLF is known to be half lactoferrin half transferrin; in this study, we show that there are different MD behavior of both iron-binding sites. While LF contains two lobes (C- and N-lobes), the C-lobe showed high fluctuations as N-lobe was more stable in the absence of ferric ions. The C-lobe and N-lobe of cLF react differently at physiological pH, revealing distinct molecular interactions between these components. In addition, cLF showed higher system flexibility derived from its larger RMSD, RMSF, lower intermolecular hydrogen bonds, and higher solvent accessible surface area (SASA).

Angiogenesis is crucial to the development of cancer because it allows the transport of oxygen, nutrients, and growth factors as well as the spread of tumors to distant organs. Inhibitors of angiogenesis prevent the formation of blood vessels that allow tumor cells to shrink, rather than promote tumor growth. Chitosan acts as a carrier for many drugs, since the compound has various properties such as biodegradable, less toxicity, more stable, simple, easy to prepare, and biocompatible. The aim of the current study was to evaluate the efficacy of chitosan nanoparticles encapsulated with troxerutin (Chi-Trox NPs) against angiogenesis and cancer in ova chick chorioallantoic membrane (CAM) model. Chi-Trox NPs were synthesized using a nanoprecipitation method and were characterized by various analyses. 24 hours' fertilized eggs (6 eggs/group) were treated with native Trox and Chi-Trox NPs for 5 days. The antiangiogenic activity was evaluated by morphometric, histopathological, immunohistochemical (CD104 and vimentin), and mRNA expression of MMP and FGF2 using RT-PCR. The anticancer activity was evaluated by histopathological, immunohistochmical (CD44), and mRNA expression of FGF2 and MMP. The synthesized chitosan NPs were successfully encapsulated with troxerutin, and the loading efficiency of chitosan NPs was found to be 86.4 ± 0.12% and 13.2 ± 0.16% respectively. Morphometric analysis of Chi-Trox NPs showed a considerable decrease in the number of blood vessels compared with control and native Trox. The histopathological observation of CAM confirmed that Chi-Trox NPs induce a significant reduction in inflammatory cells and the thickness of blood capillaries compared to control and native Trox. The immunohistochemical evaluation of CAM revealed Chi-Trox decreased CD104, vimentin and CD44 protein levels were compared with control and native Trox. Furthermore, the mRNA expression levels of FGF2 and MMP were significantly downregulated compared to their native forms. From the obtained results, Chi-Trox NPs possess significant inhibition of angiogenesis and can be used as therapeutic agents for cancer in the future.

Multidrug-resistant (MDR) pathogens have created a fatal problem for human health and antimicrobial treatment. Among the currently available antibiotics, many are inactive against MDR pathogens. In this context, heterocyclic compounds/drugs play a vital role. Thus, it is very much essential to explore new research to combat the issue. Of the available nitrogen-bearing heterocyclic compounds/drugs, pyridine derivatives are of special interest due to their solubility. Encouragingly, some of the newly synthesized pyridine compounds/drugs are found to inhibit multidrug-resistant S. aureus (MRSA). Pyridine scaffold bearing poor basicity generally improves water solubility in pharmaceutically potential molecules and has led to the discovery of numerous broad-spectrum therapeutic agents. Keeping these in mind, we have reviewed the chemistry, recent synthetic techniques, and bacterial preventative activity of pyridine derivatives since 2015. This will facilitate the development of pyridine-based novel antibiotic/drug design in the near future as a versatile scaffold with limited side effects for the next-generation therapeutics.