Antimicrobial resistance (AMR) is a ubiquitous public health menace. AMR emergence causes complications in treating infections contributing to an upsurge in the mortality rate. The epidemic of AMR in sync with a high utilization rate of antimicrobial drugs signifies an alarming situation for the fleet recovery of both animals and humans. The emergence of resistant species calls for new treatments and therapeutics. Current records propose that health drug dependency, veterinary medicine, agricultural application, and vaccination reluctance are the primary etymology of AMR gene emergence and spread. Recently, several encouraging avenues have been presented to contest resistance, such as antivirulent therapy, passive immunization, antimicrobial peptides, vaccines, phage therapy, and botanical and liposomal nanoparticles. Most of these therapies are used as cutting-edge methodologies to downplay antibacterial drugs to subdue the resistance pressure, which is a featured motive of discussion in this review article. AMR can fade away through the potential use of current cutting-edge therapeutics, advancement in antimicrobial susceptibility testing, new diagnostic testing, prompt clinical response, and probing of new pharmacodynamic properties of antimicrobials. It also needs to promote future research on contemporary methods to maintain host homeostasis after infections caused by AMR. Referable to the microbial ability to break resistance, there is a great ultimatum for using not only appropriate and advanced antimicrobial drugs but also other neoteric diverse cutting-edge therapeutics.
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.
Aim. To validate a radial quantitative ultrasound (QUS) system with dual energy X-ray absorptiometry (DXA), a criterion technique in bone status assessment among children. Methods. Bone health was evaluated using a radial QUS system (Sunlight Omnisense 8000P) to measure the speed of sound (SOS) at one-third distal radius of the nondominant hand and DXA (Hologic QDR) was used to assess whole body bone mineral density (BMD). Results. Some 29.9% of the children were grossly misclassified according to quartiles of BMD and radial SOS. Poor agreement was observed between Z-scores of radial SOS and whole-body BMD (mean difference = 0.6 ± 0.9; 95% limits of agreement = -1.4 to 2.6). With a cut-off value of -1.0, radial SOS yielded satisfactory sensitivity (80%) and specificity (93%) for the detection of children with low BMD. Conclusion. The observed poor agreement in the present study suggests that radial QUS and DXA are not comparable and hence are not interchangeable in evaluating bone status of the children.
This study was conducted to quantitatively determine the fatty acid contents of 20 species of marine fish and four species of shellfish from Straits of Malacca. Most samples contained fairly high amounts of polyunsaturated fatty acids (PUFAs), especially alpha-linolenic acid (ALA, C18:3 n3), eicosapentaenoic acid (EPA, C20:5 n3), and docosahexaenoic acid (DHA, C22:6 n3). Longtail shad, yellowstripe scad, and moonfish contained significantly higher (P < 0.05) amounts of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), respectively. Meanwhile, fringescale sardinella, malabar red snapper, black pomfret, Japanese threadfin bream, giant seaperch, and sixbar grouper showed considerably high content (537.2-944.1 mg/100 g wet sample) of desirable omega-3 fatty acids. The polyunsaturated-fatty-acids/saturated-fatty-acids (P/S) ratios for most samples were higher than that of Menhaden oil (P/S = 0.58), a recommended PUFA supplement which may help to lower blood pressure. Yellowstripe scad (highest DHA, ω - 3/ω - 6 = 6.4, P/S = 1.7), moonfish (highest ALA, ω - 3/ω - 6 = 1.9, P/S = 1.0), and longtail shad (highest EPA, ω - 3/ω - 6 = 0.8, P/S = 0.4) were the samples with an outstandingly desirable overall composition of fatty acids. Overall, the marine fish and shellfish from the area contained good composition of fatty acids which offer health benefits and may be used for nutraceutical purposes in the future.
Disability caused by migraine may be one of the main causes of burden contributing to poor quality of life (QOL) among migraine patients. Thus, this study aimed to measure QOL among migraine sufferers in comparison with healthy controls.
Background. Quaternary structures of proteins are closely relevant to gene regulation, signal transduction, and many other biological functions of proteins. In the current study, a new method based on protein-conserved motif composition in block format for feature extraction is proposed, which is termed block composition. Results. The protein quaternary assembly states prediction system which combines blocks with functional domain composition, called QuaBingo, is constructed by three layers of classifiers that can categorize quaternary structural attributes of monomer, homooligomer, and heterooligomer. The building of the first layer classifier uses support vector machines (SVM) based on blocks and functional domains of proteins, and the second layer SVM was utilized to process the outputs of the first layer. Finally, the result is determined by the Random Forest of the third layer. We compared the effectiveness of the combination of block composition, functional domain composition, and pseudoamino acid composition of the model. In the 11 kinds of functional protein families, QuaBingo is 23% of Matthews Correlation Coefficient (MCC) higher than the existing prediction system. The results also revealed the biological characterization of the top five block compositions. Conclusions. QuaBingo provides better predictive ability for predicting the quaternary structural attributes of proteins.
AIM: Qat chewing has been reported to induce subgingival microbial shifts suggestive of prebiotic-like properties. The objective here was to assess the effect of qat chewing on a panel of classical and new putative periopathogens in health and periodontitis.
MATERIALS AND METHODS: 40 qat chewers and 40 nonchewers, equally stratified by periodontal health status, were recruited. Taqman, real-time PCR was used to quantify total bacteria, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Parvimonas micra, Filifactor alocis, Synergistetes, and TM7s in pooled subgingival biofilm samples. Differences in microbial parameters between the study groups were analysed using ordinal regression.
RESULTS: In health, the qat chewers harboured significantly lower relative counts of P. gingivalis, T. forsythia, Synergistetes, and TM7s after adjustment for multiple comparisons (P ≤ 0.007). At nominal significance level, they also carried lower counts of TM7s and P. micra (P ≤ 0.05). In periodontitis, the chewers had lower counts of all taxa; however, only T. denticola withstood correction for multiple comparisons (P ≤ 0.0063).
CONCLUSIONS: Qat chewing is associated with lower proportions of periopathogens, particularly in subjects with healthy periodontium, which supports previous reports of its prebiotic-like properties. This potentially beneficial biological effect can be exploited by attempting to isolate the active fraction.
The thermoalkaline protease enzyme from pitaya (Hylocereus polyrhizus) waste was purified by a factor of 221.2 with 71.3% recovery using ammonium sulphate precipitation, gel filtration, and cation exchange chromatography. Gel filtration chromatography together with sodium dodecyl sulphate gel electrophoresis (SDS-PAGE) revealed that the enzyme is monomeric with a molecular weight of 26.7 kDa. The apparent K m and V max of the protease were 2.8 mg/mL and 31.20 u/min, respectively. The optimum pH and temperature were 8.0 and 70°C. The enzyme was highly active and stable over a wide pH range (from pH 3.0 to pH 11.0 with the optimum activity at pH 8.0). The protease has broad specificity toward azocasein, casein, hemoglobin, and gelatine. Activity of the enzyme was inhibited by Fe(2+) and Zn(2+), while protease activity was increased in the presence of Ca(2+) and Mg(2+) and Cu(2+) by factors of 125%, 110%, and 105%, respectively. The alkaline protease showed extreme stability toward surfactants and oxidizing agent. The purified protease exhibited extreme stability in the presence of organic solvents and inhibitors. In addition, the enzyme was relativity stable toward organic solvents and chelating agents, such as ethylenediaminetetraacetic acid (EDTA). The enzyme, derived from pitaya peel, possesses unique characteristics and could be used in various industrial and biotechnological applications.
A more effective vaccine against tuberculosis (TB) is urgently needed. Based on its high genetic homology with Mycobacterium tuberculosis (Mtb), the nonpathogenic mycobacteria, Mycobacterium smegmatis (Ms), could be an attractive source of potential antigens to be included in such a vaccine. We evaluated the capability of lipid-based preparations obtained from Ms to provide a protective response in Balb/c mice after challenge with Mtb H37Rv strain. The intratracheal model of progressive pulmonary TB was used to assess the level of protection in terms of bacterial load as well as the pathological changes in the lungs of immunized Balb/c mice following challenge with Mtb. Mice immunized with the lipid-based preparation from Ms either adjuvanted with Alum (LMs-AL) or nonadjuvanted (LMs) showed significant reductions in bacterial load (P < 0.01) compared to the negative control group (animals immunized with phosphate buffered saline (PBS)). Both lipid formulations showed the same level of protection as Bacille Calmette and Guerin (BCG). Regarding the pathologic changes in the lungs, mice immunized with both lipid formulations showed less pneumonic area when compared with the PBS group (P < 0.01) and showed similar results compared with the BCG group. These findings suggest the potential of LMs as a promising vaccine candidate against TB.
The present study was conducted to evaluate the antiulcerogenic effect and recognize the basic mechanism of action of Tabernaemontana divaricata (L.) R. Br. flowers. T. divaricata flower methanolic extract (TDFME) was screened for antiulcer activity versus aspirin and ethanol induced gastric ulcers at three doses--125, 250, and 500 mg/kg--orally using misoprostol as a standard. Besides histopathological examination, seven parameters, that is, ulcer index, total protein, nonprotein sulphhydryls, mucin, catalase, malondialdehyde, and superoxide dismutase levels, were estimated. In addition to HPLC profiling, GC-MS analysis and electrospray ionization--high resolution mass spectral (ESI-HRMS) analysis of crude TDFME were carried out in an attempt to identify known phytochemicals present in the extract on the basis of m/z value. The results revealed a significant increase in the levels of catalase, superoxide dismutase, mucin, and nonprotein sulphhydryls, while they revealed a reduction in ulcer index, the levels of total protein, and malondialdehyde. Histopathological observations also demonstrated the protective effect. Though all the doses of TDFME exhibited gastroprotective function, higher doses were found to be more effective. Mass spectral analysis gave a few characteristic m/z values suggesting the presence of a few known indole alkaloids, while HPLC profiling highlighted the complexity of the extract. TDFME was found to exhibit its gastroprotective effect through antioxidant mechanism and by enhancing the production of gastric mucous.
In this study, oil palm empty fruit bunch (OPEFBF) was pretreated with alkali, and lignin was extracted for further degradation into lower molecular weight phenolic compounds using enzymes and chemical means. Efficiency of monomeric aromatic compounds production from OPEFBF lignin via chemical (nitrobenzene versus oxygen) and enzymatic [cutinase versus manganese peroxidase (MnP)] approaches was investigated. The effects of sodium hydroxide concentration (2, 5, and 10% wt.) and reaction time (30, 90, and 180 minutes) on the yield of aromatic compounds were studied. The results obtained indicated that nitrobenzene oxidation produced the highest yield (333.17 ± 49.44 ppm hydroxybenzoic acid, 5.67 ± 0.25 ppm p-hydroxybenzaldehyde, 25.57 ± 1.64 ppm vanillic acid, 168.68 ± 23.23 ppm vanillin, 75.44 ± 6.71 ppm syringic acid, 815.26 ± 41.77 ppm syringaldehyde, 15.21 ± 2.19 ppm p-coumaric acid, and 44.75 ± 3.40 ppm ferulic acid), among the tested methods. High sodium hydroxide concentration (10% wt.) was needed to promote efficient nitrobenzene oxidation. However, less severe oxidation condition was preferred to preserve the hydroxycinnamic acids (p-coumaric acid and ferulic acid). Cutinase-catalyzed hydrolysis was found to be more efficient than MnP-catalyzed oxidation in the production of aromatic compounds. By hydrolyzed 8% wt. of lignin with 0.625 mL cutinase g(-1) lignin at pH 8 and 55°C for 24 hours, about 642.83 ± 14.45 ppm hydroxybenzoic acid, 70.19 ± 3.31 ppm syringaldehyde, 22.80 ± 1.04 ppm vanillin, 27.06 ± 1.20 ppm p-coumaric acid, and 50.19 ± 2.23 ppm ferulic acid were produced.
Leptospirosis is one of the zoonotic diseases in animals and humans throughout the world. LipL21 is one of the important surface-exposed lipoproteins in leptospires and the most effective cross protective immunogenic antigen. It is widely considered as a diagnostic marker for leptospirosis. In this study, we evaluated the serodiagnostic potential of LipL21 protein of Leptospira interrogans serovar Pomona. We have successfully amplified, cloned, and expressed LipL21 in E. coli and evaluated its specificity by immunoblotting. Purified recombinant LipL21 (rLipL21) was inoculated into rabbits for the production of polyclonal antibody. Characterization of the purified IgG antibody against rLipL21 was performed by cross reactivity assay. Only sera from leptospirosis patients and rabbit hyperimmune sera recognized rLipL21 while the nonleptospirosis control sera showed no reaction in immunoblotting. We confirmed that anti-rLipL21-IgG antibody cross reacted with and detected only pathogenic leptospiral species and it did not react with nonpathogenic leptospires and other bacterial species. Results observed showed that anti-rLipL21-IgG antibody has high specificity and sensitivity to leptospires. The findings indicated that the antibody could be used in a diagnostic assay for detection of leptospires or their proteins in the early phase of infection.
The potential health benefits of probiotics have long been elucidated since Metchnikoff and his coworkers postulated the association of probiotic consumption on human's health and longevity. Since then, many scientific findings and research have further established the correlation of probiotic and gut-associated diseases such as irritable bowel disease and chronic and antibiotic-associated diarrhea. However, the beneficial impact of probiotic is not limited to the gut-associated diseases alone, but also in different acute and chronic infectious diseases. This is due to the fact that probiotics are able to modify the intestinal microbial ecosystem, enhance the gut barrier function, provide competitive adherence to the mucosa and epithelium, produce antimicrobial substances, and modulate the immune activity by enhancing the innate and adaptive immune response. Nevertheless, the current literature with respect to the association of probiotic and cancer, high serum cholesterol, and allergic and HIV diseases are still scarce and controversial. Therefore, in the present work, we reviewed the potential preventive and therapeutic role of probiotics for cancer, high serum cholesterol, and allergic and HIV diseases as well as providing its possible mechanism of actions.
Probiotics are live microorganisms that exert beneficial effects on the host, when administered in adequate amounts. Mostly, probiotics affect the gastrointestinal (GI) tract of the host and alter the composition of gut microbiota. Nowadays, the incidence of hip fractures due to osteoporosis is increasing worldwide. Ovariectomized (OVX) rats have fragile bone due to estrogen deficiency and mimic the menopausal conditions in women. Therefore, this study aimed to examine the effects of Bifidobacterium longum (B. longum) on bone mass density (BMD), bone mineral content (BMC), bone remodeling, bone structure, and gene expression in OVX rats. The rats were randomly assigned into 3 groups (sham, OVX, and the OVX group supplemented with 1 mL of B. longum 10(8)-10(9) colony forming units (CFU)/mL). B. longum was given once daily for 16 weeks, starting from 2 weeks after the surgery. The B. longum supplementation increased (p < 0.05) serum osteocalcin (OC) and osteoblasts, bone formation parameters, and decreased serum C-terminal telopeptide (CTX) and osteoclasts, bone resorption parameters. It also altered the microstructure of the femur. Consequently, it increased BMD by increasing (p < 0.05) the expression of Sparc and Bmp-2 genes. B. longum alleviated bone loss in OVX rats and enhanced BMD by decreasing bone resorption and increasing bone formation.
The objective of this study was to isolate, identify, and characterize some lactic acid bacterial strains from human milk, infant feces, and fermented grapes and dates, as potential probiotics with antimicrobial activity against some human pathogenic strains. One hundred and forty bacterial strains were isolated and, after initial identification and a preliminary screening for acid and bile tolerance, nine of the best isolates were selected and further identified using 16 S rRNA gene sequences. The nine selected isolates were then characterized in vitro for their probiotic characteristics and their antimicrobial activities against some human pathogens. Results showed that all nine isolates belonged to the genus Lactobacillus. They were able to tolerate pH 3 for 3 h, 0.3% bile salts for 4 h, and 1.9 mg/mL pancreatic enzymes for 3 h. They exhibited good ability to attach to intestinal epithelial cells and were not resistant to the tested antibiotics. They also showed good antimicrobial activities against the tested pathogenic strains of humans, and most of them exhibited stronger antimicrobial activity than the reference strain L. casei Shirota. Thus, the nine Lactobacillus strains could be considered as potential antimicrobial probiotic strains against human pathogens and should be further studied for their human health benefits.
Stress shielding and micromotion are two major issues which determine the success of newly designed cementless femoral stems. The correlation of experimental validation with finite element analysis (FEA) is commonly used to evaluate the stress distribution and fixation stability of the stem within the femoral canal. This paper focused on the applications of feature extraction and pattern recognition using support vector machine (SVM) to determine the primary stability of the implant. We measured strain with triaxial rosette at the metaphyseal region and micromotion with linear variable direct transducer proximally and distally using composite femora. The root mean squares technique is used to feed the classifier which provides maximum likelihood estimation of amplitude, and radial basis function is used as the kernel parameter which mapped the datasets into separable hyperplanes. The results showed 100% pattern recognition accuracy using SVM for both strain and micromotion. This indicates that DSP could be applied in determining the femoral stem primary stability with high pattern recognition accuracy in biomechanical testing.
Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP₆ extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP₆ was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP₆ markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP₆ had also markedly decreased β-catenin and COX-2 in colon tumors. Thus, the downregulation of β-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP₆ and thereby act as a potent anticancer agent.
This study aimed to identify Listeria spp. and L. monocytogenes, characterize the isolates, and determine the antibiotic resistance profiles of the isolates Listeria spp. and L. monocytogenes in fresh produce, fertilizer, and environmental samples from vegetable farms (organic and conventional farms). A total of 386 samples (vegetables, soil, water, and fertilizer with manure) were examined. The identification of bacterial isolates was performed using PCR and characterized using ERIC-PCR and BOX-PCR. The discriminating power of the typing method was analyzed using Simpson's Index of Diversity. Thirty-four (n=34) Listeria isolates were subjected to antimicrobial susceptibility test using the disc-diffusion technique. The PCR analysis revealed that Listeria spp. were present in 7.51% (29/386) of all the samples (vegetable, soil, fertilizer, and water). None of the samples examined were positive for the presence of L. monocytogenes. Percentages of 100% (15/15) and 73.30% (11/15) of the Listeria spp. isolated from vegetables, fertilizer, and soil from organic farm B had indistinguishable DNA fingerprints by using ERIC-PCR and BOX-PCR, respectively. Listeria spp. isolated from 86 samples of vegetable, fertilizer, and environment of organic farm A and conventional farm C had distinct DNA fingerprints. Simpson's Index of Diversity, D, of ERIC-PCR and BOX-PCR is 0.604 and 0.888, respectively. Antibiotic susceptibility test revealed that most of the Listeria spp. in this study were found to be resistant to ampicillin, rifampin, penicillin G, tetracycline, clindamycin, cephalothin, and ceftriaxone. The isolates had MAR index ranging between 0.31 and 0.85. In conclusion, hygienic measures at farm level are crucial to the reduction of Listeria transmission along the food chain.
Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.
This study aims to identify the predictors in the different aspects of the health-related quality of life (HRQoL) and to measure the changes of functional status over time in a cohort of Nigerian stroke survivors. A prospective observational study was conducted in three hospitals of Kano state of Nigeria where stroke survivors receive rehabilitation. The linguistic-validated Hausa versions of the stroke impact scale 3.0, modified Rankin scale, Barthel index and Beck depression inventory scales were used. Paired samples t-test was used to calculate the amount of changes that occur over time and the forward stepwise linear regression model was used to identify the predictors. A total of 233 stroke survivors were surveyed at 6 months, and 93% (217/233) were followed at 1 year after stroke. Functional disabilities were significantly reduced during the recovery phase. Motor impairment, disability, and level of depression were independent predictors of HRQoL in the multivariate regression analysis. The involvement of family members as caregivers is the key factor for those survivors with improved functional status. Thus, to enhance the quality of poststroke life, it is proposed that a holistic stroke rehabilitation service and an active involvement of family members are established at every possible level.