Displaying publications 61 - 80 of 161 in total

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  1. Sivaprakasam S, Mohd Azim Khan NA, Yee Fan T, Kumarasan Y, Sicheritz-Pontén T, Petersen B, et al.
    Microbiol Resour Announc, 2024 Apr 11;13(4):e0113723.
    PMID: 38506531 DOI: 10.1128/mra.01137-23
    Here, we present the complete genome of a plant growth-promoting strain, Bacillus stratosphericus AIMST-CREST02 isolated from the bulk soil of a high-yielding paddy plot. The genome is 3,840,451 bp in size with a GC content of 41.25%. Annotation predicted the presence of 3,907 coding sequences, including genes involved in auxin biosynthesis regulation and gamma-aminobutyric acid (GABA) metabolism.
  2. Khan AH, López-Maldonado EA, Khan NA, Villarreal-Gómez LJ, Munshi FM, Alsabhan AH, et al.
    Chemosphere, 2022 Mar;291(Pt 3):133088.
    PMID: 34856242 DOI: 10.1016/j.chemosphere.2021.133088
    Solid waste generation has rapidly increased due to the worldwide population, urbanization, and industrialization. Solid waste management (SWM) is a significant challenge for a society that arises local issues with global consequences. Thus, solid waste management strategies to recycle waste products are promising practices that positively impact sustainable goals. Several developed countries possess excellent solid waste management strategies to recycle waste products. Developing countries face many challenges, such as municipal solid waste (MSW) sorting and handling due to high population density and economic instability. This mismanagement could further expedite harmful environmental and socioeconomic concerns. This review discusses the current solid waste management and energy recovery production in developing countries; with statistics, this review provides a comprehensive revision on energy recovery technologies such as the thermochemical and biochemical conversion of waste with economic considerations. Furthermore, the paper discusses the challenges of SWM in developing countries, including several immediate actions and future policy recommendations for improving the current status of SWM via harnessing technology. This review has the potential of helping municipalities, government authorities, researchers, and stakeholders working on MSW management to make effective decisions for improved SWM for achieving sustainable development.
  3. Abdul Rahman NS, Mohamed Noor Khan NA, Eshak Z, Sarbandi MS, Mohammad Kamal AA, Abd Malek M, et al.
    Antioxidants (Basel), 2022 Oct 25;11(11).
    PMID: 36358471 DOI: 10.3390/antiox11112100
    Vitrification is an important tool to store surplus embryos in assisted reproductive technology (ART). However, vitrification increases oxidative damage and results in decreased viability. Studies have reported that L-glutathione (GSH) supplementation improves the preimplantation development of murine embryos. Glutathione constitutes the major non-protein sulphydryl compound in mammalian cells, which confers protection against oxidative damage. However, the effect of GSH supplementation on embryonic vitrification outcomes has yet to be reported. This study aims to determine whether GSH supplementation in culture media improves in vitro culture and vitrification outcomes, as observed through embryo morphology and preimplantation development. Female BALB/c mice aged 6−8 weeks were superovulated through an intraperitoneal injection of 10 IU of pregnant mare serum gonadotrophin (PMSG), followed by 10 IU of human chorionic gonadotrophin (hCG) 48 h later. The mated mice were euthanized by cervical dislocation 48 h after hCG to harvest embryos. Two-cell embryos were randomly assigned to be cultured in either Group 1 (GSH-free medium), Group 2 (GSH-free medium with vitrification), Group 3 (0.01 mM GSH-supplemented medium), or Group 4 (0.01 mM GSH-supplemented medium with vitrification). Non-vitrified (Groups 1 and 3) and vitrified (Groups 2 and 4) embryos were observed for morphological quality and preimplantation development at 24, 48, 72, and 96 h. In the non-vitrified groups, there were significant increases in the number of Grade-1 blastocysts in GSH cultures (p < 0.05). Similarly, in the vitrified groups, GSH supplementation was also seen to significantly increase blastocyst formation. Exogenous GSH supplementation resulted in a significant increase in intracellular GSH, a release of cytochrome c from mitochondria, and a parallel decrease in intracellular reactive oxygen species (ROS) levels in vitrified eight-cell embryos (p < 0.05). GSH supplementation was shown to upregulate Bcl2 expression and downregulate Bax expression in the vitrified preimplantation embryo group. The action of exogenous GSH was concomitant with an increase in the relative abundance of Gpx1 and Sod1. In conclusion, our study demonstrated the novel use and practical applicability of GSH supplementation for improving embryonic cryotolerance via a decrease in ROS levels and the inhibition of apoptotic events by improvement in oxidative status.
  4. Magosso E, Ansari MA, Gopalan Y, Abu Bakar MR, Karim Khan NA, Wong JW, et al.
    PMID: 21073069
    Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and a frequent finding on ultrasound examination. NAFLD is considered as the liver component of metabolic syndrome and is linked to accelerated atherosclerosis and cardiovascular disease. No data from systematic studies regarding the prevalence of NAFLD are available for the Malaysian population. One hundred eighty untreated hypercholesterolemic volunteers underwent blood and ultrasound examinations to evaluate their livers. NAFLD was diagnosed in 102 subjects (56.7%) with similar prevalences between sexes. Of the 102 positive subjects 82 (80.4%) were graded as mild, 17 (16.7%) as moderate and 3 (2.9%) as severe fatty liver cases. Elevated fasting plasma glucose (FPG) levels were found in 13 of 180 subjects (7.2%), while elevated AST and ALT levels were seen in 30 (16.7%) and 22 (12.2%) of the180 subjects, respectively.
  5. Khan AH, Aziz HA, Khan NA, Dhingra A, Ahmed S, Naushad M
    Sci Total Environ, 2021 Nov 10;794:148484.
    PMID: 34217082 DOI: 10.1016/j.scitotenv.2021.148484
    The occurrence of pharmaceutical residues in the aquatic ecosystem is an emerging concern of environmentalists. This study primarily investigated the seasonal variation of high-priority pharmaceutical residues in the Yamuna River, accompanied by 22 drains discharge from different parts of Delhi. Five sampling sites were selected for analyzing high-priority pharmaceuticals along with physico-chemical and biological parameters for 3 season's viz. pre-monsoon (PrM), monsoon (DuM), and post-monsoon (PoM), respectively. The maximum occurrences were detected during the PoM, compared to the PrM and DuM seasons. The maximum concentration of BOD, COD, and Phosphate was detected at the last sampling station (SP-5). Similarly, all targeted pharmaceuticals concentration were maximum at the last sampling point i.e. Okhla barrage (SP-5, max: DIC = 556.1 ng/l, IBU = 223.4 ng/l, CAR = 183.1 ng/l, DIA = 457.8 ng/l, OFL = 1726.5 ng/l, FRU = 312.2 ng/l and SIM = 414.9 ng/l) except at Barapulla downstream (SP-4, max: ERY = 178.1 ng/l). The mean concentrations of Fecal coliform (FC) ranged from 1700 to 6500 CFU/100 ml. The maximum colonies were detected in PrM season (6500 CFU/100 ml) followed by PoM (5800 CFU/100 ml) and least in DuM (1700 CFU/100 ml). Risk quotient (RQ) analysis of high-priority pharmaceuticals indicated high ecotoxicological risks exposure (>1) from DIC, DIA, OFL, and SIM in all seasons at all the sampling sites. However, lower risk was predicted for IBU, CAR, ERY, and FRU, respectively. This risk assessment indicated an aquatic ecosystem potentially exposed to high risks from these pharmaceutical residues. Moreover, seasonal agricultural application, rainfall, and temperature could influence the levels and compositions of pharmaceutical residue in the aquatic ecosystem. Hence, attention is required particularly to this stream since it is only a local lifeline source for urban consumers for domestic water supply and farmers for cultivation.
  6. Algarni S, Khan RA, Khan NA, Mubarak NM
    Environ Sci Pollut Res Int, 2021 Dec;28(46):65822-65831.
    PMID: 34322813 DOI: 10.1007/s11356-021-15534-6
    Building and its environment are in focus owing to health impact attributed to indoor air quality. This study was carried out to assess indoor air quality in terms of particulate matter (PM) and carbon dioxide in a residential building, during COVD-19 pandemic lockdown from March 25 to April 23, 2020, Abha, Saudi Arabia. The PM concentration range for kitchen, bedroom, and hall were 40,000-81000 μg/m3 (PM0.3), 15,000-26000 μg/m3 (PM0.5), 4000-6000 μg/m3 (PM1), 1100-1500 μg/m3 (PM2.5), 160-247 μg/m3 (PM5), and 60-95 μg/m3 (PM10). The results of this study suggest that bedroom needs to be ventilated as CO2 concentration was reaching 700 ppm during sleep hours. PM concentration was exceeding 300 μg/m3 (unhealthy) for all particle sizes of PM0.3, PM0.5, PM1, and PM2.5 except for PM10 which was also above safe limits (0-50 μg/m3). Also, with influential habit (aromatic smoke), these concentrations increased 2-28 times for PM. The hazard quotient value greater than 1 revealed potential health risk to the inhabitants. Hence, future studies are needed for developing indoor air quality guidelines for residential buildings in Saudi Arabia and better planning and management of energy consumption.
  7. Low BY, Liong ML, Yuen KH, Chee C, Leong WS, Chong WL, et al.
    J Urol, 2008 Apr;179(4):1461-9.
    PMID: 18295277 DOI: 10.1016/j.juro.2007.11.060
    PURPOSE: We determined the clinical efficacy and safety of terazosin in the treatment of patients with female lower urinary tract symptoms.
    MATERIALS AND METHODS: A total of 100 females 20 to 70 years old who met the inclusion criteria of total International Prostate Symptom Score 8 or greater, symptom duration 1 or more months, and did not meet any exclusion criteria were entered into the study. Subjects were randomized to receive terazosin or placebo in titrated dose from 1 mg od, 1 mg twice daily to 2 mg twice daily during 14 weeks. Successful treatment outcomes use primary end point of International Prostate Symptom Score quality of life 2 or less and secondary end point of total International Prostate Symptom Score 7 or less. Other outcome measures included International Prostate Symptom Score individual item scores, King's Health Questionnaire quality of life domains, objective assessment parameters of 24-hour frequency volume chart, maximum flow rate and post-void residual urine.
    RESULTS: Using a primary end point, 32 of 40 (80%) evaluable terazosin subjects responded in contrast to 22 of 40 (55%) evaluable placebo subjects (p <0.02). The secondary end point revealed a successful outcome in 85% of terazosin subjects vs 55% in placebo (p <0.01). Of the 7 International Prostate Symptom Score individual item scores, only item scores of frequency and straining showed statistically significant reductions with terazosin (p <0.01). All King's Health Questionnaire quality of life domains except domain of severity measures showed statistically significant improvement with terazosin (p <0.05). There were no differences between treatment groups in all objective assessment parameters. Of all evaluable subjects 23 of 40 (58%) on placebo experienced adverse events vs 16 of 40 (40%) on terazosin (p >0.05).
    CONCLUSIONS: Terazosin proved to be more effective and safe than placebo in patients with female lower urinary tract symptoms.
  8. Khairuddin S, Ngo FY, Lim WL, Aquili L, Khan NA, Fung ML, et al.
    J Clin Med, 2020 Oct 12;9(10).
    PMID: 33053848 DOI: 10.3390/jcm9103260
    Major depression contributes significantly to the global disability burden. Since the first clinical study of deep brain stimulation (DBS), over 406 patients with depression have now undergone this neuromodulation therapy, and 30 animal studies have investigated the efficacy of subgenual cingulate DBS for depression. In this review, we aim to provide a comprehensive overview of the progress of DBS of the subcallosal cingulate in humans and the medial prefrontal cortex, its rodent homolog. For preclinical animal studies, we discuss the various antidepressant-like behaviors induced by medial prefrontal cortex DBS and examine the possible mechanisms including neuroplasticity-dependent/independent cellular and molecular changes. Interestingly, the response rate of subcallosal cingulate Deep brain stimulation marks a milestone in the treatment of depression. DBS among patients with treatment-resistant depression was estimated to be approximately 54% across clinical studies. Although some studies showed its stimulation efficacy was limited, it still holds great promise as a therapy for patients with treatment-resistant depression. Overall, further research is still needed, including more credible clinical research, preclinical mechanistic studies, precise selection of patients, and customized electrical stimulation paradigms.
  9. Lee SW, Liong ML, Yuen KH, Leong WS, Cheah PY, Khan NA, et al.
    Urology, 2008 Jan;71(1):79-84.
    PMID: 18242370 DOI: 10.1016/j.urology.2007.08.043
    OBJECTIVES: To examine the prevalence, characteristics, and impact of sexual dysfunction in our primary care referral population.
    METHODS: Participants seeking treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) were recruited from general urology clinics. The subjects completed the National Institutes of Health-Chronic Prostatitis Symptom Index, International Index of Erectile Function-5, and selected questions from the University of Washington Symptom Score. Additional information on demographics and medical and treatment history were also obtained. Sexual dysfunction was defined as self-reported erectile dysfunction (ED) or ejaculatory difficulty, or both.
    RESULTS: Of 296 participants with CP/CPPS, 214 (72.3%) reported sexual dysfunction. The National Institutes of Health-Chronic Prostatitis Symptom Index total score averaged 22.5 +/- 6.9 for participants with sexual dysfunction compared with 20.4 +/- 7.8 for participants who did not report sexual dysfunction (P = 0.03). Of the 214 participants with sexual dysfunction, 54 (25.0%) complained of ED only, 71 (33.4%) complained of ejaculatory difficulties only, and 89 (41.6%) complained of both ED and ejaculatory difficulties. Men reporting both ED and ejaculatory difficulty reported worse CP/CPPS symptoms (analysis of variance, P = 0.042) and worse quality of life (analysis of variance, P = 0.006) than men without sexual dysfunction.
    CONCLUSIONS: Sexual dysfunction was reported by almost three quarters of patients with CP/CPPS. Patients with CP/CPPS and sexual dysfunction experienced substantially worse symptoms, particularly worse quality of life, than other patients with CP/CPPS. Sexual dysfunction merits consideration as an important aspect of CP/CPPS and a potential outcome measure.

    Study site: general urology clinics
    in Penang
  10. Khan RA, Khan NA, El Morabet R, Alsubih M, Khan AR, Khan S, et al.
    Environ Res, 2023 Jan 01;216(Pt 1):114437.
    PMID: 36181898 DOI: 10.1016/j.envres.2022.114437
    Pharmaceutical compounds being able to alter, retard, and enhance metabolism has gained attention in recent time as emerging pollutant. However, hospitals which are part of every urban landscape have yet to gain attention in terms of its hospital wastewater treatment to inhibit pharmaceutical compounds from reaching environment. Hence this study evaluated performance of constructed wetland in combination with tubesettler and aeration based on removal efficiency and ecological risk assessment (HQ). The removal efficiency of constructed wetland with plantation was higher by 31% (paracetamol), 102% (ibuprofen), 46%, (carbamazepine), 57% (lorazepam), 54% (erythromycin), 31% (ciprofloxacin) and 20% (simvastatin) against constructed wetland without plantation. Constructed wetland with aeration efficiency increased for paracetamol, ibuprofen, carbamazepine, lorazepam, erythromycin, ciprofloxacin, and simvastatin removal efficiency were higher by 58%, 130%, 52%, 79%, 107%, 57%, and 29% respectively. In constructed wetland with plantation, removal efficiency was higher by 20% (paracetamol), 13% (ibuprofen), 4% (carbamazepine), 14% (lorazepam), 34% (erythromycin), 19% (ciprofloxacin) and 7% (simvastatin). High ecological risk was observed for algae, invertebrate and fish with hazard quotient values in range of 2.5-484, 10-631 and 1-78 respectively. This study concludes that if space is the limitation at hospitals aeration with constructed wetland can be adopted. If space is available, constructed wetland with tubesettler is suitable, economic and environmentally friendly option. Future research works can focus on evaluating other processes combination with constructed wetland.
  11. Rehman IU, Wu DB, Ahmed R, Khan NA, Rahman AU, Munib S, et al.
    Medicine (Baltimore), 2018 08;97(31):e10764.
    PMID: 30075491 DOI: 10.1097/MD.0000000000010764
    BACKGROUND: Pruritus adds to the complications of chronic kidney disease (CKD) patient and a well-recognized complication among the CKD patients. Majority of the patients on hemodialysis experience a generalized pruritus and patients reported being moderately to extremely disturbed by at least one of the sleep-related condition. This study aim to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus.

    METHODS: A multicentered, open-label, parallel group, prospective randomized controlled trial among patients suffering from CKD-associated pruritus with sleep disturbance, after randomization into control, and intervention group to be held at North West General Hospital and Research Center Peshawar, Pakistan and Institute of Kidney Diseases Peshawar, Pakistan.

    RESULTS: The primary outcome is to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-associated pruritus. After baseline assessment by Urdu version of 5D itch scale and Urdu version of Pittsburgh Sleep Quality Index (PSQI) and Urdu EQ-5D 3L, the intervention group will be given zolpidem 10 mg oral tablets and control group with acupressure on both foots on KI-1 acupoints for total of 6 minutes. Assessment will be done at weeks 4 and 8 from baseline by using Urdu version of 5D itch scale and Urdu version of PSQI and Urdu EQ-5D 3L, whereas safety profiling of zolpidem 10 mg tablet at week 6 from baseline and acupressure acceptability at week 6 from baseline. Analysis of covariance will be used to examine the differences in treatment effects between the intervention and control groups.

    CONCLUSION: Improvement of sleep quality and quality of life among patients with CKD-associated pruritus requires great importance. This study aims to improve the quality of sleep and quality of life among patients with hemodialysis suffering from CKD-associated pruritus.

  12. Rehman IU, Ahmed R, Rahman AU, Wu DBC, Munib S, Shah Y, et al.
    Medicine (Baltimore), 2021 May 28;100(21):e25995.
    PMID: 34032717 DOI: 10.1097/MD.0000000000025995
    BACKGROUND: Chronic kidney disease (CKD)-associated pruritus (CKD-aP) contributes to poor quality of life, including reduced sleep quality and poor sleep quality is a source of patient stress and is linked to lower health-related quality of life. This study aimed to investigate the effectiveness of zolpidem 10 mg and acupressure therapy on foot acupoints to improve the sleep quality and overall quality of life among hemodialysis patients suffering from CKD-aP.

    METHOD: A multicenter, prospective, randomized, parallel-design, open label interventional study to estimate the effectiveness of zolpidem (10 mg) oral tablets versus acupressure on sleep quality and quality of life in patients with CKD-aP on hemodialysis. A total of 58 hemodialysis patients having sleep disturbance due to CKD-aP completed the entire 8-week follow-up. The patients were divided into a control (acupressure) group of 28 patients and an intervention (zolpidem) group of 30 patients.

    RESULTS: A total of 58 patients having CKD-aP and sleep disturbance were recruited. In the control group there was a reduction in the PSQI score with a mean ± SD from 12.28 ± 3.59 to 9.25 ± 3.99, while in the intervention group the reduction in PSQI score with a mean ± SD was from 14.73 ± 4.14 to 10.03 ± 4.04 from baseline to endpoint. However, the EQ5D index score and EQ-visual analogue scale (VAS) at baseline for the control group with a mean ± SD was 0.49 ± 0.30 and 50.17 ± 8.65, respectively, while for the intervention group the values were 0.62 ± 0.26 and 47.17 ± 5.82, respectively. The mean EQ5D index score in the control group improved from 0.49 ± 0.30 to 0.53 ± 0.30, but in the intervention group there was no statistical improvement in mean EQ5D index score from 0.62 ± 0.26 to 0.62 ± 0.27 from baseline to week 8. The EQ 5D improved in both groups and the EQ-VAS score was 2.67 points higher at week 8 as compared to baseline in the control group, while in the intervention group the score was 3.33 points higher at week 8 as compared to baseline. Comparing with baseline, the PSQI scores were significantly reduced after week 4 and week 8 (P =  

  13. Aqeel Y, Siddiqui R, Farooq M, Khan NA
    Exp Parasitol, 2015 Oct;157:170-6.
    PMID: 26297676 DOI: 10.1016/j.exppara.2015.08.007
    Acanthamoeba is an opportunistic protist pathogen that is responsible for serious human and animal infection. Being one of the most frequently isolated protists from the environment, it is likely that it readily encounters microaerophilic environments. For respiration under anaerobic or low oxygen conditions in several amitochondriate protists, decarboxylation of pyruvate is catalyzed by pyruvate ferredoxin oxidoreductase instead of pyruvate dehydrogenase. In support, Nitazoxanide, an inhibitor of pyruvate ferredoxin oxidoreductase, is effective and non-mutagenic clinically against a range of amitochondriate protists, Giardia intestinalis, Entamoeba histolytica and Trichomonas vaginalis. The overall aim of the present study was to determine in vitro efficacy of Nitazoxanide against Acanthamoeba castellanii. At micromolar concentrations, the findings revealed that Nitazoxanide neither affected A. castellanii growth or viability nor amoeba-mediated host cell monolayer damage in vitro or extracellular proteolytic activities. Similarly, microaerophilic conditions alone had no significant effects. In contrast, microaerophilic conditions together with Nitazoxanide showed amoebicidal effects and inhibited A. castellanii-mediated host cell monolayer damage as well as extracellular proteases. Using encystation assays, it was observed that Nitazoxanide inhibited trophozoite transformation into cysts both under aerophilic and microaerophilic conditions. Furthermore, pre-treatment of cysts with Nitazoxanide inhibited A. castellanii excystation. These findings are important in the identification of potential targets that could be useful against parasite-specific respiration as well as to understand the basic biology of the life cycle of Acanthamoeba.
  14. Siddiqui R, Kulsoom H, Lalani S, Khan NA
    Exp Parasitol, 2016 Jul;166:94-6.
    PMID: 27055361 DOI: 10.1016/j.exppara.2016.04.001
    Balamuthia mandrillaris is a protist pathogen that can cause encephalitis with a mortality rate of more than 95%. Early diagnosis followed by aggressive treatment is a pre-requisite for successful prognosis. Current methods for identifying this organism rely on culture and microscopy, antibody-based methods using animals, or involve the use of molecular tools that are expensive. Here, we describe the isolation of antibody fragments that can be used for the unequivocal identification of B. mandrillaris. B. mandrillaris-specific antibody fragments were isolated from a bacteriophage antibody display library. Individual clones were studied by enzyme-linked immunosorbent assay, and immunofluorescence. Four antibody clones showed specific binding to B. mandrillaris. The usefulness of phage antibody display technology as a diagnostic tool for isolating antibody fragments against B. mandrillaris antigens and studying their biological role(s) is discussed further.
  15. Siddiqui R, Aqeel Y, Khan NA
    Cont Lens Anterior Eye, 2016 Oct;39(5):389-93.
    PMID: 27133448 DOI: 10.1016/j.clae.2016.04.004
    Acanthamoeba castellanii is the causative agent of blinding keratitis. Though reported in non-contact lens wearers, it is most frequently associated with improper use of contact lens. For contact lens wearers, amoebae attachment to the lens is a critical first step, followed by amoebae binding to the corneal epithelial cells during extended lens wear. Acanthamoeba attachment to surfaces (biological or inert) and migration is an active process and occurs during the trophozoite stage. Thus retaining amoebae in the cyst stage (dormant form) offers an added preventative measure in impeding parasite traversal from the contact lens onto the cornea. Here, we showed that as low as 3% DMSO, abolished A. castellanii excystation. Based on the findings, it is proposed that DMSO should be included in the contact lens disinfectants as an added preventative strategy against contracting Acanthamoeba keratitis.
  16. Siddiqui R, Saleem S, Khan NA
    Exp Parasitol, 2016 Jun 18;168:16-24.
    PMID: 27327524 DOI: 10.1016/j.exppara.2016.06.006
    The treatment of Acanthamoeba infections remains problematic, suggesting that new targets and/or chemotherapeutic agents are needed. Bioassay-guided screening of drugs that are clinically-approved for non-communicable diseases against opportunistic eukaryotic pathogens is a viable strategy. With known targets and mode of action, such drugs can advance to clinical trials at a faster pace. Recently Bortezomib (proteasome inhibitor) has been approved by FDA in the treatment of multiple myeloma. As proteasomal pathways are well known regulators of a variety of eukaryotic cellular functions, the overall aim of the present study was to study the effects of peptidic and non-peptidic proteasome inhibitors on the biology and pathogenesis of Acanthamoeba castellanii of the T4 genotype, in vitro. Zymographic assays revealed that inhibition of proteasome had detrimental effects on the extracellular proteolytic activities of A. castellanii. Proteasome inhibition affected A. castellanii growth (using amoebistatic assays), but not viability of A. castellanii. Importantly, proteasome inhibitors affected encystation as determined by trophozoite transformation into the cyst form, as well as excystation, as determined by cyst transformation into the trophozoite form. The ability of proteasome inhibitor to block Acanthamoeba differentiation is significant, as it presents a major challenge in the successful treatment of Acanthamoeba infection. As these drugs are used clinically against non-communicable diseases, the findings reported here have the potential to be tested in a clinical setting against amoebic infections.
  17. Yousuf FA, Rafiq S, Siddiqui R, Khan NA
    Microb Pathog, 2016 Apr;93:145-51.
    PMID: 26867478 DOI: 10.1016/j.micpath.2016.02.002
    The completion of Escherichia coli K1 genome has identified several genomic islands that are present in meningitis-causing E. coli RS218 but absent in the non-pathogenic E. coli MG1655. In this study, the role of various genomic islands in E. coli K1 interactions with intestinal epithelial cells (Caco-2) and kidney epithelial cells (MA104) was determined. Using association assays, invasion assays, and intracellular survival assays, the findings revealed that the genomic island deletion mutants of RS218 related to P fimbriae, S fimbriae, F17-like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, protein secretion system (T1SS for hemolysin; T2SS; T5SS for antigen 43), Iro system and hmu system), invasins (CNF1, IbeA), toxins (α-hemolysin), K1 capsule biosynthesis, metabolism (d-serine catabolism, dihydroxyacetone, glycerol, and glyoxylate metabolism), prophage genes, showed reduced interactions with both cell types. Next, we determined the role of various genomic islands in E. coli K1 resistance to serum. When exposed to the normal human serum, the viability of the genomic island deletion mutants related to adhesins such as S fimbriae, P fimbriae, F17-like fimbriae, non-fimbrial adhesins, Hek and hemagglutinin, antigen 43 and T5SS for antigen 43, T2SS, and T1SS for hemolysin, Iro system and hmu system, prophage genes, metabolism (sugar metabolism and d-serine catabolism), K1 capsule biosynthesis, and invasins such as CNF1 was affected, suggesting their role in bacteremia. The characterization of these genomic islands should reveal mechanisms of E. coli K1 pathogenicity that could be of value as therapeutic targets.
  18. Baig AM, Khan NA
    Microb Pathog, 2015 Nov;88:48-51.
    PMID: 26276705 DOI: 10.1016/j.micpath.2015.08.005
    Granulomatous amoebic encephalitis due to Acanthamoeba is a chronic disease that almost always results in death. Hematogenous spread is a pre-requisite followed by amoebae invasion of the blood-brain barrier to enter the central nervous system. Given the systemic nature of this infection, a significant latent period of several months before the appearance of clinical manifestations is puzzling. Based on reported cases, here we propose pathogenetic mechanisms that explain the above described latency of the disease.
  19. Ali SM, Siddiqui R, Ong SK, Shah MR, Anwar A, Heard PJ, et al.
    Appl Microbiol Biotechnol, 2017 Jan;101(1):253-286.
    PMID: 27743045 DOI: 10.1007/s00253-016-7872-2
    Infectious diseases remain a significant threat to human health, contributing to more than 17 million deaths, annually. With the worsening trends of drug resistance, there is a need for newer and more powerful antimicrobial agents. We hypothesized that animals living in polluted environments are potential sources of antimicrobials. Under polluted milieus, organisms such as cockroaches encounter different types of microbes, including superbugs. Such creatures survive the onslaught of superbugs and are able to ward off disease by producing antimicrobial substances. Here, we characterized antibacterial properties in extracts of various body organs of cockroaches (Periplaneta americana) and showed potent antibacterial activity in crude brain extract against methicillin-resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1. The size-exclusion spin columns revealed that the active compound(s) are less than 10 kDa in molecular mass. Using cytotoxicity assays, it was observed that pre-treatment of bacteria with lysates inhibited bacteria-mediated host cell cytotoxicity. Using spectra obtained with LC-MS on Agilent 1290 infinity liquid chromatograph, coupled with an Agilent 6460 triple quadruple mass spectrometer, tissues lysates were analysed. Among hundreds of compounds, only a few homologous compounds were identified that contained the isoquinoline group, chromene derivatives, thiazine groups, imidazoles, pyrrole-containing analogs, sulfonamides, furanones, and flavanones and known to possess broad-spectrum antimicrobial properties and anti-inflammatory, anti-tumour, and analgesic properties. Further identification, characterization, and functional studies using individual compounds can act as a breakthrough in developing novel therapeutics against various pathogens including superbugs.
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