Publications by authors named "Ashraf Khan"

136 Publications

Alleviation of Memory Deficit by Bergenin via the Regulation of Reelin and Nrf-2/NF-κB Pathway in Transgenic Mouse Model.

Int J Mol Sci 2021 Jun 20;22(12). Epub 2021 Jun 20.

Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.

The present study aims to determine the neuroprotective effect of Bergenin against spatial memory deficit associated with neurodegeneration. Preliminarily, the protective effect of Bergenin was observed against HO-induced oxidative stress in HT-22 and PC-12 cells. Further studies were performed in 5xFAD Tg mouse model by administering Bergenin (1, 30 and 60 mg/kg; orally), whereas Bergenin (60 mg/kg) significantly attenuated the memory deficit observed in the Y-maze and Morris water maze (MWM) test. Fourier transform-infrared (FT-IR) spectroscopy displayed restoration of lipids, proteins and their derivatives compared to the 5xFAD Tg mice group. The differential scanning calorimeter (DSC) suggested an absence of amyloid beta (Aβ) aggregation in Bergenin-treated mice. The immunohistochemistry (IHC) analysis suggested the neuroprotective effect of Bergenin by increasing Reelin signaling (Reelin/Dab-1) and attenuated Aβ (1-42) aggregation in hippocampal regions of mouse brains. Furthermore, IHC and western blot results suggested antioxidant (Keap-1/Nrf-2/HO-1), anti-inflammatory (TLR-4/NF-kB) and anti-apoptotic (Bcl-2/Bax/Caspase-3) effect of Bergenin. Moreover, a decrease in Annexin V/PI-stained hippocampal cells suggested its effect against neurodegeneration. The histopathological changes were reversed significantly by Bergenin. In addition, a remarkable increase in antioxidant level with suppression of pro-inflammatory cytokines, oxidative stress and nitric oxide production were observed in specific regions of the mouse brains.
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http://dx.doi.org/10.3390/ijms22126603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234641PMC
June 2021

Suppression of TRPV1/TRPM8/P2Y Nociceptors by Withametelin via Downregulating MAPK Signaling in Mouse Model of Vincristine-Induced Neuropathic Pain.

Int J Mol Sci 2021 Jun 4;22(11). Epub 2021 Jun 4.

Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.

Vincristine (VCR) is a widely used chemotherapy drug that induced peripheral painful neuropathy. Yet, it still lacks an ideal therapeutic strategy. The transient receptor potential (TRP) channels, purinergic receptor (P2Y), and mitogen-activated protein kinase (MAPK) signaling play a crucial role in the pathogenesis of neuropathic pain. Withametelin (WMT), a potential Phytosteroid isolated from , exhibits remarkable neuroprotective properties. The present investigation was designed to explore the effect of withametelin on VCR-induced neuropathic pain and its underlying molecular mechanism. Initially, the neuroprotective potential of WMT was confirmed against hydrogen peroxide (HO)-induced PC12 cells. To develop potential candidates for neuropathic pain treatment, a VCR-induced neuropathic pain model was established. Vincristine (75 μg/kg) was administered intraperitoneally (i.p.) for 10 consecutive days (day 1-10) for the induction of neuropathic pain. Gabapentin (GBP) (60 mg/kg, i.p.) and withametelin (0.1 and 1 mg/kg i.p.) treatments were given after the completion of VCR injection on the 11th day up to 21 days. The results revealed that WMT significantly reduced VCR-induced pain hypersensitivity, including mechanical allodynia, cold allodynia, and thermal hyperalgesia. It reversed the VCR-induced histopathological changes in the brain, spinal cord, and sciatic nerve. It inhibited VCR-induced changes in the biochemical composition of the myelin sheath of the sciatic nerve. It markedly downregulated the expression levels of TRPV1 (transient receptor potential vanilloid 1); TRPM8 (Transient receptor potential melastatin 8); and P2Y nociceptors and MAPKs signaling, including ERK (Extracellular Signal-Regulated Kinase), JNK (c-Jun -terminal kinase), and p-38 in the spinal cord. It suppressed apoptosis by regulating Bax (Bcl2-associated X-protein), Bcl-2 (B-cell-lymphoma-2), and Caspase-3 expression. It considerably attenuated inflammatory cytokines, oxidative stress, and genotoxicity. This study suggests that WMT treatment suppressed vincristine-induced neuropathic pain by targeting the TRPV1/TRPM8/P2Y nociceptors and MAPK signaling.
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http://dx.doi.org/10.3390/ijms22116084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200233PMC
June 2021

Clinical Characteristics of COVID-19-Infected Cancer Patients in Pakistan: Differences Between Survivors and Non-Survivors.

Front Oncol 2021 20;11:655634. Epub 2021 May 20.

Department of Pathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan.

Background: Cancer patients are considered as highly vulnerable individuals in the current COVID-19 pandemic. We studied the clinical characteristics of survivor and non-survivor COVID-19-infected cancer patients in Pakistan.

Patients And Methods: We did a retrospective study of 70 cancer patients with PCR-confirmed COVID-19 infection from Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore and Peshawar, Pakistan between April 13 and July 09, 2020. These patients were discharged from the hospital or had died by July 09, 2020. Clinical, pathological and radiological characteristics were compared between survivors and non-survivors by fisher's exact test and chi-square test. Univariable and multivariable logistic regression models were performed to explore the risk factors of mortality.

Results: Seventy cancer patients with SARS-CoV-2 infection were enrolled and the majority were males 38 (54.3%). 57 (81.4%) had solid tumors and 13 (18.6%) had hematological malignancies. Dyspnea (44 cases) was the most common symptom (62.9%). Complications were reported in 51 (72.9%) patients during the course of disease. 19 (27.1%) patients were admitted to an intensive care unit (ICU). A significant increase in the C-reactive protein level and neutrophil count was observed in the deceased patients as compared to the surviving patients. D-dimer values of ≥0.2 mg/L were significantly associated with mortality (=0.01). We identified two independent risk factors associated with death, ICU admission (=0.007) and D-dimer (=0.003).

Conclusion: Pakistani cancer patients with COVID-19 infection reported poor prognosis. Intensive surveillance of clinicopathological characteristics of cancer patients infected with COVID-19 especially D-dimer values may play a pivotal role in the outcome of the disease.
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http://dx.doi.org/10.3389/fonc.2021.655634DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173078PMC
May 2021

Feasibility of dual-contrast fluorescence imaging of pathological breast tissues.

J Biophotonics 2021 08 26;14(8):e202100007. Epub 2021 May 26.

Advanced Biophotonics Laboratory, University of Massachusetts Lowell, Lowell, Massachusetts, USA.

The combination of intravital dye, methylene blue (MB), with molecular cancer marker, pH low insertion peptide (pHLIP) conjugated with fluorescent Alexa532 (Alexa532-pHLIP), was evaluated for enhancing contrast of pathological breast tissue ex vivo. Fresh, thick breast specimens were stained sequentially with Alexa532-pHLIP and aqueous MB and imaged using dual-channel fluorescence microscopy. MB and Alexa532-pHLIP accumulated in the nuclei and cytoplasm of cancer cells, respectively. MB also stained nuclei of normal cells. Some Alexa532-pHLIP fluorescence emission was detected from connective tissue and benign cell membranes. Overall, Alexa532-pHLIP showed high affinity to cancer, while MB highlighted tissue morphology. The results indicate that MB and Alexa532-pHLIP provide complementary information and show promise for the detection of breast cancer.
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http://dx.doi.org/10.1002/jbio.202100007DOI Listing
August 2021

Enhancing the antibacterial efficacy of aluminum foil by nanostructuring its surface using hot water treatment.

Nanotechnology 2021 May 19;32(32). Epub 2021 May 19.

Department of Physics and Astronomy, University of Arkansas at Little Rock, Little Rock, AR 72204, United States of America.

Bacterial biofilm has become one of the most frequent health problems as it contributes to persistent chronic infections. Therefore, it is vital to find alternatives to currently used bactericidal agents to prevent bacterial contamination on surfaces effectively and prevent the biofilms formation. Several metallic materials are well known for their antimicrobial activity; this includes copper, copper alloys, silver, gold, titanium, and zinc. On the other hand, some metals, such as aluminum, do not have noteworthy antimicrobial properties. In this study, we demonstrate that the antibacterial activity of household aluminum foil can be enhanced by nanostructuring the foil's surface by a simple hot water treatment (HWT) process. Cultures ofandwere grown on nutrient agar while exposed to the samples of treated and untreated Al foils and left for 24 h. Our results indicate that treated Al foil can more effectively inhibit the bacteria growth compared to the regular untreated Al foil. This enhancement in antibacterial property might be due to a combination of chemical and morphological changes that the cell undergoes once it encounters nanofeatures of HWT-Al foil surface.
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http://dx.doi.org/10.1088/1361-6528/abfd59DOI Listing
May 2021

Topical delivery of curcumin-loaded transfersomes gel ameliorated rheumatoid arthritis by inhibiting NF-κβ pathway.

Nanomedicine (Lond) 2021 04 26;16(10):819-837. Epub 2021 Apr 26.

Department of Pharmacy, Quaid-i-Azam University, Islamabad 45320, Pakistan.

To fabricate and evaluate curcumin-loaded transfersomes (Cur-TF) for the targeted delivery and enhanced therapeutic efficacy of curcumin for the treatment of rheumatoid arthritis (RA). Modified thin-film hydration method was used to prepare Cur-TF which were then embedded into carbopol-934 gel. They were further evaluated through techniques and in an arthritis model. Cur-TF had optimal particle size, spherical morphology, high encapsulation efficiency and sustained drug release profiles. The Cur-TF gel had better skin penetration than plain curcumin. findings demonstrated improved clinical, histological and x-ray scores and reduced pro-inflammatory cytokines through NF-κβ inhibition. Cur-TF gel delivered curcumin to the arthritic dermal tissue through a topical route and demonstrated promising therapeutic efficacy by significantly alleviating complete Freud's adjuvant (CFA)-induced arthritis.
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http://dx.doi.org/10.2217/nnm-2020-0316DOI Listing
April 2021

Inhibition of NF-κB signaling and HSP70/HSP90 proteins by newly synthesized hydrazide derivatives in arthritis model.

Naunyn Schmiedebergs Arch Pharmacol 2021 07 13;394(7):1497-1519. Epub 2021 Mar 13.

Pharmacological Sciences Research Lab, Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

In the current study, the N-benzylidene-4-((2-hydroxynaphthalene-1-yl) diazenyl) hydrazides (NCHDH and NTHDH) were evaluated against the Carrageenan- and CFA-induced models. During the preliminary investigation, the NCHDH and NTHDH treatment showed marked anti-inflammatory and analgesic activity against the Carrageenan-induced acute model. Once the anti-inflammatory activity was established against acute Carrageenan model, the NCHDH and NTHDH were evaluated against the chronic CFA-induced arthritis model. The NCHDH and NTHDH treatment markedly attenuated the inflammatory and analgesic parameters compared to CFA-treated group. Furthermore, the increase in the oxidative stress and attenuation of antioxidant enzymes has been reported following CFA administration. However, NCHDH and NTHDH treatment significantly induced the antioxidants and attenuated the oxidative stress markers. The CFA administration showed marked tailing of DNA; however, the NCHDH- and NTHDH-treated group preserved DNA integrity. Furthermore, the histological studies showed marked alteration in the CFA-treated group; however, the NCHDH and NTHDH treatment markedly improved the histological features. The Western blot, immunohistology, and ELISA assay revealed marked increase in the Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), Jun N-terminal Kinase (JNK), TNF-α, and COX-2 levels; however, the NCHDH and NTHDH attenuated their expressions significantly. Similarly, the NCHDH and NTHDH significantly induced the mRNA expression levels of heat shock proteins. The computational analysis showed significant binding interaction with various protein targets via multiple hydrogens, and hydrophobic bonds. The in vivo pharmacokinetic study was also performed to assess the various pharmacokinetic parameters. In conclusion, the NCHDH and NTHDH treatment showed significant anti-arthritic activity against Carrageenan and CFA models.
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http://dx.doi.org/10.1007/s00210-021-02075-5DOI Listing
July 2021

HSV-infection-related herpetic anogenital ulcer disease among PLWH in southeastern US: electronic medical record based analysis.

Sex Transm Infect 2021 Jan 12. Epub 2021 Jan 12.

Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama, USA

ObjectivesThe southeastern US is a domestic epicentre for incident HIV with high prevalence of herpes simplex virus (HSV) coinfection. We estimated the incidence rates (IR) of symptomatic herpetic anogenital ulcer disease (HAUD) and assessed its associations with demographic and clinical characteristics, specifically with immunological markers using median, nadir and trajectory CD4 counts.

Methods: Electronic medical records (EMR) of over 7000 people living with HIV (PLWH) attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analysed. IR of HSV-related HAUD were estimated per 10 000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of IR. All IR and trends were stratified by gender and race. Six CD4 trajectory groups were constructed using the group-based trajectory modelling. Multivariable logistic models were conducted to assess the associations of CD4 counts (nadir, median CD4 and newly defined CD4 trajectory), separately with HAUD.

Results: Of the 4484 PLWH eligible individuals (3429 men, 1031 women and 24 transgender), we observed 425 patients with HSV-related HAUD. The mean logviral load was higher in HAUD than HAUD-free groups, whereas the median nadir CD4 count (cells/uL) was higher in the non-cases than the case groups (p<0.05). HAUD were more frequent in women than men. Median CD4 (<200 cell/uL) was associated with HAUD (OR=2.1), but there were no significant associations with nadir CD4. Significant associations with declining and sustained low CD4 counts trajectory patterns were observed with HAUD.

Conclusions: There were significant differences between men and women with incident HAUD among PLWH. EMR-based studies can provide innovative trajectory models that can potentially be helpful in guiding screening and clinical care of HAUD among high-risk PLWH.
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http://dx.doi.org/10.1136/sextrans-2020-054503DOI Listing
January 2021

Molecular analysis of a rare case of low-grade primary peritoneal serous carcinoma in a male.

Rare Tumors 2020 9;12:2036361320979219. Epub 2020 Dec 9.

Department of Pathology, University of Massachusetts Memorial Medical Center, Worcester, MA, USA.

Primary peritoneal serous carcinomas (PPSC) are exceedingly rare in male patients. Only a few cases were reported, and mostly with the limited immunophenotypical characterization. No molecular analysis of PPSC in males has been previously performed. We here describe another case of PPSC in a male patient. A comprehensive molecular analysis of the tumor revealed SF3B1 gene mutation as a possible driver.
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http://dx.doi.org/10.1177/2036361320979219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734543PMC
December 2020

Stability-Indicating Method Development and Validation for Busulfan Drug Substance by Gas Chromatography-Flame Ionization Detector.

J Chromatogr Sci 2021 Jan;59(2):112-119

Compendial Development Laboratory, United States Pharmacopeia, Rockville, MD 20852, USA.

A new, simple and stability-indicating gas chromatography-flame ionization detection (GC-FID) method was developed and validated for the quantitative determination of busulfan and its organic impurities (OI) in drug substance without derivatization. The chromatographic attributes were achieved on a fused silica capillary column (0.53 mm × 30 m, 1.0 μm, USP Phase G42), using hydrogen as a carrier gas with a split ratio of 1:1. Forced degradation studies were conducted to establish the stability-indicating capability and method specificity that showed the stressed busulfan peak was free from any co-elution. Robustness study demonstrated the chromatograms remained mostly unaffected under deliberate, but small variations of chromatographic parameters, establishing the reliability of the method during routine usage. The method was shown to be reliable, sensitive, specific, linear, accurate, precise and rugged in the 1,4-butanediol concentration range of 1-20 μg/mL. The method, intended for compendial uses, is suitable for quantitative analysis of busulfan and its organic impurities in drug substances.
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http://dx.doi.org/10.1093/chromsci/bmaa093DOI Listing
January 2021

Antimicrobial resistance and related gene analysis of Salmonella from egg and chicken sources by whole-genome sequencing.

Poult Sci 2020 Dec 12;99(12):7076-7083. Epub 2020 Oct 12.

Division of Microbiology, Office of Regulatory Science, Center for Food Safety and Nutrition, U.S. Food and Drug Administration, College Park, MD. Electronic address:

Whole-genome sequencing (WGS) is a valuable tool in research on foodborne pathogens. In this study, a total of 143 isolates of Salmonella serotypes Enteritidis, Typhimurium, and Heidelberg sourced from eggs and chickens were analyzed for their antimicrobial resistance profiles using WGS data. The isolates carried high rate of genes resistant to aminoglycoside (70.63%), tetracycline (26.57%), fosfomycin (25.17%), sulfonamides (23.78%), and β-lactamases (15.38%); and aadA was the most frequently observed antimicrobial resistance gene (ARG). Antimicrobial resistance varies by Salmonella serotypes, with Salmonella enterica serovar Enteritidis (Salmonella ser. Enteritidis) isolates being highly resistant to aminoglycoside (particularly streptomycin); Salmonella ser. Typhimurium more resistant to aminoglycoside, tetracycline, and sulfonamides; and Salmonella ser. Heidelberg more resistant to aminoglycoside and fosfomycin. Salmonella ser. Typhimurium isolates presented more varieties of ARG than Salmonella ser. Enteritidis and Salmonella ser. Heidelberg. Our data showed that 5 isolates of Salmonella ser. Typhimurium and Salmonella ser. Heidelberg contained ARG resistant to ≥ 5 antimicrobials. In addition, 23 Salmonella isolates carried ARG resistant to 4 antimicrobials.
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http://dx.doi.org/10.1016/j.psj.2020.10.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705029PMC
December 2020

The newly synthesized compounds (NCHDH and NTHDH) attenuates LPS-induced septicemia and multi-organ failure via Nrf2/HO1 and HSP/TRVP1 signaling in mice.

Chem Biol Interact 2020 Sep 4;329:109220. Epub 2020 Aug 4.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan. Electronic address:

The sepsis is considered as serious clinic-pathological condition related with high rate of morbidity and mortality in critical care settings. In the proposed study, the hydrazides derivatives N-(benzylidene)-2-((2-hydroxynaphthalen-1-yl)diazenyl)benzohydrazides (1-2) (NCHDH and NTHDH) were investigated against the LPS-induced sepsis in rodents. The NCHDH and NTHDH markedly improved the physiological sign and symptoms associated with the sepsis such as mortality, temperature, and clinical scoring compared to negative control group, which received only LPS (i.p.). The NCHDH and NTHDH also inhibited the production of the NO and MPO compared to the negative control. Furthermore, the treatment control improved the histological changes markedly of all the vital organs. Additionally, the Masson's trichrome and PAS (Periodic Acid Schiff) staining also showed improvement in the NCHDH and NTHDH treated group in contrast to LPS-induced group. The antioxidants were enhanced by the intervention of the NCHDH and NTHDH and the level of the MDA and POD were attenuated marginally compared to the LPS-induced group. The hematology study showed marked improvement and the reversal of the LPS-induced changes in blood composition compared to the negative control. The synthetic function of the liver and kidney were preserved in the NCHDH and NTHDH treated group compared to the LPS-induced group. The NCHDH and NTHDH markedly enhanced the Nrf2, HO-1 (Heme oxygenase-1), while attenuated the Keap1 and TRPV1 expression level as compared to LPS treated group. Furthermore, the NCHDH and NTHDH treatment showed marked increased in the mRNA expression level of the HSP70/90 proteins compared to the negative control.
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http://dx.doi.org/10.1016/j.cbi.2020.109220DOI Listing
September 2020

CD4 Trajectory Models and Onset of Non-AIDS-Defining Anal Genital Warts, Precancer, and Cancer in People Living With HIV Infection-1.

Sex Transm Dis 2020 Sep;47(9):628-633

From the Department of Epidemiology, School of Public Health.

Background: It is unclear how the characteristics of CD4 counts predict non-AIDS-defining human papillomavirus-related anogenital warts (AGWs) and anal high-grade squamous intraepithelial lesions/cancer (HSIL) in people living with HIV infection-1 (PLWH). We compared the associations between 3 CD4 counts measures and these disease outcomes in the study.

Methods: Retrospective sociobehavioral and clinical data from electronic health records of 4803 PLWH from 2006 to 2018 were included. Three different measurements of CD4 counts-(a) nadir, (b) median, and (c) trajectory-were estimated. Six CD4 trajectory groups were constructed using the group-based trajectory modeling from all patients older than 18 years with ≥3 clinical visits. Univariate and multivariable logistic regression models were used to assess the associations with AGW and HSIL, separately.

Results: A total of 408 AGW, 102 anal HSIL (43 HSIL, 59 cancer), 4 penile cancer, and 15 vaginal cancer cases were observed. Median CD4 (<200 cell/μL) was associated with AGW (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.6-3.0]), and anal HSIL (OR, 2.7 [95% CI, 1.5-5.0]; each, P < 0.001). Low nadir CD4 (<200 cell/μL) was associated with AGW (OR, 1.8 [95% CI, 1.3-2.6]) and anal HSIL (OR, 2.4 [95% CI, 1.2-4.7]; each, P ≤ 0.001). Different patterns (declining and sustained low CD4 counts) of CD4 trajectories showed the strongest associations with onset of both AGW (OR, 1.8-3.1) and HSIL (OR, 2.7-6.7).

Conclusions: People living with HIV infection-1 with the same median CD4 could have very different CD4 trajectories, implying different dynamics of immune status. CD4 trajectory could be a better predictor of incident AGW and HSIL among PLWH.
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http://dx.doi.org/10.1097/OLQ.0000000000001215DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447125PMC
September 2020

Development of novel pH-sensitive nanoparticle-based transdermal patch for management of rheumatoid arthritis.

Nanomedicine (Lond) 2020 03 26;15(6):603-624. Epub 2020 Feb 26.

Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan.

To formulate and evaluate a pH-responsive nanoparticle (NP)-based patch for efficient transdermal delivery of flurbiprofen against rheumatoid arthritis. Nanoprecipitation technique was used for preparation of NPs and central composite design was employed for optimization purposes. Optimized NPs were loaded into the transdermal patch by the solvent evaporation method. Prepared NPs exhibited an average size of 69 nm, while NPs loaded onto the transdermal patch showed sustained release and high permeation through the skin. In studies, the prepared carrier system elucidated high therapeutic potential in both acute and chronic inflammatory models as evident from the results of behavioral, radiological, histopathological and antioxidant analyses. The flurbiprofen-loaded pH-sensitive NP-based transdermal patch has the potential to manage rheumatoid arthritis effectively.
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http://dx.doi.org/10.2217/nnm-2019-0385DOI Listing
March 2020

Comorbidities associated with HPV infection among people living with HIV-1 in the southeastern US: a retrospective clinical cohort study.

BMC Infect Dis 2020 Feb 14;20(1):144. Epub 2020 Feb 14.

Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, Birmingham, AL, 35242, USA.

Background: The southeastern US is an epicenter for incident HIV in the US with high prevalence of human papillomavirus (HPV) co-infections. However, epidemiologies of HPV-associated clinical conditions (CC) among people living with HIV-1 infection (PLWH) are not fully known.

Methods: Electronic medical records (EMR) of PLWH attending one of the leading HIV clinics in the southeastern US between 2006 and 2018 were reviewed and analyzed. The retrospective study was nested within the University of Alabama at Birmingham HIV clinical cohort, which has electronically collected over 7000 PLWH's clinical and sociobehavioral data since 1999. Incidence rates of HPV-related CC including anogenital warts, penile, anal, cervical, and vaginal/vulvar low- and high-grade squamous intraepithelial lesions (LSIL and HSIL) were estimated per 10,000 person years. Joinpoint regressions were performed to examine temporal changes in the trends of incident CC. All rates and trends were stratified by gender and race.

Results: Of the 4484 PLWH included in the study (3429 men, 1031 women, and 24 transgender), we observed 1038 patients with HPV-related CC. The median nadir CD4 count (cells/uL) was higher in the HPV-condition free group than the case groups (P < 0.0001). Anogenital warts, anal LSIL, HSIL, and cancer were more likely to be diagnosed among HIV-infected men than women. White men presented more frequently with anal LSIL and anal and penile cancers than black men (P < 0.03). White women were also more likely to be diagnosed with cervical HSIL (P = 0.023) and cancer (P = 0.037) than black women.

Conclusions: There were significant differences between gender and race with incidence of HPV-related CC among HIV patients. EMR-based studies provide insights on understudied HPV-related anogenital conditions in PLWH; however, large-scale studies in other regions are needed to generalize current findings and draw public health attention to co-infection induced non-AIDS defining comorbidities among PLWH.
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http://dx.doi.org/10.1186/s12879-020-4822-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7023731PMC
February 2020

Continentalic acid exhibited nephroprotective activity against the LPS and E. coli-induced kidney injury through inhibition of the oxidative stress and inflammation.

Int Immunopharmacol 2020 Mar 28;80:106209. Epub 2020 Jan 28.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan. Electronic address:

The present study investigated the effect of the continentalic acid (CNT) isolated from the Aralia Continentalis against the LPS and E. coli-induced nephrotoxicity. The LPS and E. coli administration markedly altered the behavioral parameters including spontaneous pain, tail suspension and survival rate. However, the treatment with CNT dose dependently improved the behavioral parameters. The CNT treatment significantly improved the renal functions test (RFTs) and hematological parameters following LPS and E. coli-induced kidney injury. Furthermore, the LPS and E. coli administration markedly compromised the anti-oxidant enzymes and enhanced the oxidative stress markers. However, the CNT treatment markedly enhanced the anti-oxidants enzymes such as GSH, GST, Catalase and SOD, while attenuated the oxidative stress markers such as MDA and POD. The MPO enzyme is widely used marker for the neutrophilic infiltration, the LPS and E. coli administration markedly increased the MPO activity. However, the CNT treatment markedly attenuated the MPO activity in both LPS and E. coli-induced kidney injury. Furthermore, the CNT treatment markedly attenuated the NO production compared to the LPS and E. coli-induced kidney injury group. Additionally, the CNT treatment improved the histological parameters markedly (H and E, PAS and Masson's trichome staining) and protect the kidney from the inflammatory insult of the LPS and E. coli evidently. The comet assay revealed marked DNA damage, however, the CNT treatment markedly prevented the LPS and E. coli-induced kidney damage. The CNT treatment markedly enhanced the expression of Nrf2, while attenuated the iNOS expression in both models of kidney injury.
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http://dx.doi.org/10.1016/j.intimp.2020.106209DOI Listing
March 2020

Mucoprotective effects of Saikosaponin-A in 5-fluorouracil-induced intestinal mucositis in mice model.

Life Sci 2019 Dec 19;239:116888. Epub 2019 Oct 19.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, 45320, Pakistan. Electronic address:

5-Fluorouracil (5-FU)-induced intestinal mucositis (IM) is one of the most common oncological problem. It involves serious clinical consequences such as diarrhea, erythematous lesions of mucosa, and eventually development of ulcers accompanied by severe pain. The aim of the present study was to demonstrate the mucoprotective effects of Saikosaponin-A in 5-FU-induced intestinal mucositis in mice. Mucositis was induced in BALB/c mice by intraperitoneal injection of 5-FU (50 mg/kg/day) for three consecutive days and IM was assessed by both behavioral and histochemical analysis. While, Saikosaponin-A (1, 5, 10 mg/kg/day) was administered 1 h before 5-FU injection for consecutive seven days. Pre-treatment of Saikosaponin-A significantly ameliorated the severity of mucositis reflected as food intake, body weight loss, severity of diarrhea and mortality rate in a dose depended manner as compared to mice treated with 5-FU. Moreover, histopathological analysis furthered reinforced the mucoprotective potential of Saikosaponin-A against 5-FU-induced intestinal abnormalities referred as villus atrophy, mitotic crypt stem cells damage, inflammatory cells infiltration, vacuolization and edema. Furthermore, Saikosaponin-A administration strongly inhibited pro-inflammatory mediators (TNF-α, COX-2, IL-1β and IL-6) and apoptotic markers (p-JNK, Casp-3). Saikosaponin-A pre-treatment significantly reduced the production of nitric oxide (NO) in intestinal tissue, inhibited acetic acid-induced Evans blue vascular permeability. The Siaikosaponin-A treatment markedly enhanced the anti-oxidants enzymes (Nrf2, HO-1, SOD, GSH, GST and Catalase), while decreased the oxidative stress markers i.e. Malonaldehde (MDA). Hence, these data suggest that Saikosaponin-A maybe a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.
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http://dx.doi.org/10.1016/j.lfs.2019.116888DOI Listing
December 2019

Anti-hyperalgesic properties of a flavanone derivative Poncirin in acute and chronic inflammatory pain models in mice.

BMC Pharmacol Toxicol 2019 09 11;20(1):57. Epub 2019 Sep 11.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Background: Poncirin is flavanone derivative (isolated from Poncirus trifoliata) with known pharmacological activities such as anti-tumor, anti-osteoporotic, anti-inflammatory and anti-colitic. The present study aimed to explore the anti-allodynic and anti-hyperalgesic potentials of poncirin in murine models of inflammatory pain.

Methods: The analgesic potential of poncirin was evaluated in formalin-, acetic acid-, carrageenan- and Complete Freund's Adjuvant (CFA)-induced inflammatory pain models in mice. Anti-allodynic and anti-hyperalgesic activities were measured using Von Frey filaments, Randall Selitto, hotplate and cold acetone tests. The serum nitrite levels were determined using Griess reagent. The Quantitative Real-time PCR (qRT-PCR) was performed to assess the effect of poncirin on mRNA expression levels of inflammatory cytokines and anti-oxidant enzymes.

Results: Intraperitoneal administration of poncirin (30 mg/kg) markedly reduced the pain behavior in both acetic acid-induced visceral pain and formalin-induced tonic pain models used as preliminary screening tools. The poncirin (30 mg/kg) treatment considerably inhibited the mechanical hyperalgesia and allodynia as well as thermal hyperalgesia and cold allodynia. The qRT-PCR analysis showed noticeable inhibition of pro-inflammatory cytokines (mRNA expression levels of TNF-α, IL-1β and IL-6) (p < 0.05) in poncirin treated group. Similarly, poncirin treatment also enhanced the mRNA expressions levels of anti-oxidant enzymes such as transcription factor such as nuclear factor (erythroid-derived 2)-like 2 (Nrf2) (p < 0.05), heme oxygenase (HO-1) (p < 0.05) and superoxide dismutase (SOD2) (p < 0.05). Chronic treatment of poncirin for 6 days did not confer any significant hepatic and renal toxicity. Furthermore, poncirin treatment did not altered the motor coordination and muscle strength in CFA-induced chronic inflammatory pain model.

Conclusion: The present study demonstrated that poncirin treatment significantly reduced pain behaviors in all experimental models of inflammatory pain, suggesting the promising analgesic potential of poncirin in inflammatory pain conditions.
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http://dx.doi.org/10.1186/s40360-019-0335-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6737657PMC
September 2019

Benign Breast Cyst in a Young Male.

Cureus 2019 Jun 3;11(6):e4814. Epub 2019 Jun 3.

Department of Radiology, University of Massachusetts Medical School, Worcester, USA.

Simple benign breast cysts are commonly diagnosed in female breasts and may present as palpable masses. However, they are extremely uncommon in the male breast and are rarely reported in the literature. Here, we report a case of a simple benign cyst of the breast in a relatively healthy 37-year-old man. The patient initially presented with a palpable 2-3 mm tender left breast lump. Further evaluation with mammography and ultrasound revealed a mass most consistent with a simple benign cyst. However, considering the rarity of breast cysts in males, the lesion was biopsied to rule out malignancy. Pathology results from ultrasound-guided core needle biopsy demonstrated fibro-adipose tissue with a benign cyst lined by foamy cells with apocrine features, consistent with a diagnosis of a benign epithelial cyst and concordant with the radiological findings. To our knowledge, this is the youngest case of a benign breast cyst in a male that has been reported in the literature. In this case report, we discuss the typical features and presentation of breast cysts in males, associated imaging findings on mammography and ultrasound, and the necessity for pathological confirmation with biopsy in this population.
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http://dx.doi.org/10.7759/cureus.4814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682391PMC
June 2019

Gene expression signature of atypical breast hyperplasia and regulation by SFRP1.

Breast Cancer Res 2019 06 27;21(1):76. Epub 2019 Jun 27.

Pioneer Valley Life Sciences Institute, Springfield, MA, 01199, USA.

Background: Atypical breast hyperplasias (AH) have a 10-year risk of progression to invasive cancer estimated at 4-7%, with the overall risk of developing breast cancer increased by ~ 4-fold. AH lesions are estrogen receptor alpha positive (ERα+) and represent risk indicators and/or precursor lesions to low grade ERα+ tumors. Therefore, molecular profiles of AH lesions offer insights into the earliest changes in the breast epithelium, rendering it susceptible to oncogenic transformation.

Methods: In this study, women were selected who were diagnosed with ductal or lobular AH, but no breast cancer prior to or within the 2-year follow-up. Paired AH and histologically normal benign (HNB) tissues from patients were microdissected. RNA was isolated, amplified linearly, labeled, and hybridized to whole transcriptome microarrays to determine gene expression profiles. Genes that were differentially expressed between AH and HNB were identified using a paired analysis. Gene expression signatures distinguishing AH and HNB were defined using AGNES and PAM methods. Regulation of gene networks was investigated using breast epithelial cell lines, explant cultures of normal breast tissue and mouse tissues.

Results: A 99-gene signature discriminated the histologically normal and AH tissues in 81% of the cases. Network analysis identified coordinated alterations in signaling through ERα, epidermal growth factor receptors, and androgen receptor which were associated with the development of both lobular and ductal AH. Decreased expression of SFRP1 was also consistently lower in AH. Knockdown of SFRP1 in 76N-Tert cells resulted altered expression of 13 genes similarly to that observed in AH. An SFRP1-regulated network was also observed in tissues from mice lacking Sfrp1. Re-expression of SFRP1 in MCF7 cells provided further support for the SFRP1-regulated network. Treatment of breast explant cultures with rSFRP1 dampened estrogen-induced progesterone receptor levels.

Conclusions: The alterations in gene expression were observed in both ductal and lobular AH suggesting shared underlying mechanisms predisposing to AH. Loss of SFRP1 expression is a significant regulator of AH transcriptional profiles driving previously unidentified changes affecting responses to estrogen and possibly other pathways. The gene signature and pathways provide insights into alterations contributing to AH breast lesions.
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http://dx.doi.org/10.1186/s13058-019-1157-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598287PMC
June 2019

Dedifferentiated Carcinoma of the Endometrium Associated With Low-grade Müllerian Adenosarcoma: A Clinicopathologic Case Report Including the Immunohistochemical and Molecular Profile.

Int J Gynecol Pathol 2020 Mar;39(2):141-145

Dedifferentiated carcinoma is defined as undifferentiated carcinoma coexisting with a second component of FIGO grade 1 or 2 endometrioid carcinoma. It is a rare entity with highly aggressive behavior. Dedifferentiated carcinoma combined with another primary uterine tumor is even rarer. We describe a case containing 3 different morphologies comprised of a dedifferentiated carcinoma associated with a low-grade endometrioid carcinoma coexisting with a low-grade Müllerian adenosarcoma. We also used targeted genomic analysis to show all 3 components arise from the same founding clone and identify novel mutations that drive tumor progression.
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http://dx.doi.org/10.1097/PGP.0000000000000584DOI Listing
March 2020

Bangladesh Chars Tobacco Assessment Project (CTAP) 2018: a data note.

BMC Res Notes 2018 Dec 20;11(1):914. Epub 2018 Dec 20.

BRAC University, 66 Mohakhali, Dhaka, 1206, Bangladesh.

Objectives: The Chars Tobacco Assessment Project 2018 is a holistic survey conducted in the chars (riverine islands) of Gaibandha in Northern Bangladesh, covering 985 households over 24 clusters. The survey was conducted with two objectives: (1) to assess levels of tobacco consumption and evaluate prevailing socio-economic, behavioral and health status of the chars population, and (2) to look at the effectiveness of advocacy campaigns to reduce tobacco consumption through behavioral nudges via randomized controlled trials (RCTs) in rural Bangladesh. The study site was purposively chosen due to its high tobacco consumption rate, and the geographical segregation of the chars aided in reducing spillovers for RCT design.

Data Description: In addition to detailed information on tobacco (smoking and smokeless) consumption and perception, data was collected on: household composition, housing and plot ownership, consumption, risks and shocks coping, dowry, farm production, loans, savings and lending, labor income, asset holdings, migration and remittance, anthropometry, respiratory diseases, co-morbidities, reproductive history, risk and time preference. Unique to the dataset are carbon monoxide readings for accurate short term smoking measurement and FEV1 and PEF values for identification of long term lung damage. The data is representative only for the chars of Gaibandha.
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http://dx.doi.org/10.1186/s13104-018-4015-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302286PMC
December 2018

Accuracy of biometric formulae in hypermetropic patients undergoing cataract surgery.

Eur J Ophthalmol 2019 Sep 1;29(5):510-515. Epub 2018 Oct 1.

Princess Alexandra Eye Pavilion, Edinburgh, UK.

Purpose: To audit and analyse the accuracy of current biometric formulae on refractive outcomes following cataract surgery in patients with axial length less than 22 mm.

Methods: A total of 84 eyes from 84 patients with axial length <22 mm were identified from consecutive patients undergoing cataract surgery retrospectively at a single university hospital. All subjects had biometry using the IOLMaster (Carl Zeiss Meditec, Inc, Dublin, CA, USA) and a Sensar AR40 intraocular lens implant (Abbott Medical Optics, CA, USA). One eye from each patient was randomly selected for inclusion. Prediction errors were calculated by comparing expected refraction from optimized formulas (SRK/T, Hoffer Q, Haigis and Holladay 1) to postoperative refraction. A national survey of ophthalmologists was conducted to ascertain biometric formula preference for small eyes.

Results: The mean axial length was 21.00 ± 0.55 mm. Mean error was greatest for Hoffer Q at -0.57 dioptres. There was no significant difference in mean absolute error between formulae. SRK/T achieved the highest percentage of outcomes within 0.5 dioptres (45.2%) and 1 dioptre (76.2%) of target. Shallower anterior chamber depth was associated with higher mean absolute error for SRK/T (p = 0.028), Hoffer Q (p = 0.003) and Haigis (p = 0.016) but not Holladay (p = 0.111).

Conclusion: SRK/T had the highest proportion of patients achieving refractive results close to predicted outcomes. However, there was a significant association between a shallower anterior chamber depth and higher mean absolute error for all formulae except Holladay 1. This suggests that anterior chamber depth with axial length should be considered when counselling patients about refractive outcome.
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http://dx.doi.org/10.1177/1120672118803509DOI Listing
September 2019

Analysis of enterotoxigenic Bacillus cereus strains from dried foods using whole genome sequencing, multi-locus sequence analysis and toxin gene prevalence and distribution using endpoint PCR analysis.

Int J Food Microbiol 2018 Nov 27;284:31-39. Epub 2018 Jun 27.

U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Applied Research and Safety Assessment, Laurel, MD 20708 USA.

Bacillus cereus strains were isolated from dried foods, which included international brands of spices from South East Asia, Mexico and India purchased from several retail stores, samples of powdered infant formula (PIF), medicated fish feed and dietary supplements. The genetic diversity of 64 strains from spices and PIF was determined using a multiplex endpoint PCR assay designed to identify hemolysin BL, nonhemolytic enterotoxin, cytotoxin K, and enterotoxin FM toxin genes. Thirteen different B. cereus toxigenic gene patterns or profiles were identified among the strains. Randomly selected B. cereus strains were sequenced and compared with reference Genomic Groups from National Center Biotechnology Information using bioinformatics tools. A comprehensive multi-loci sequence analysis (MLSA) was designed using alleles from 25 known MLST genes specifically tailored for use with whole genome assemblies. A cohort of representative genomes of strains from a few FDA regulated commodities like dry foods and medicated fish feed was used to demonstrate the utility of the 25-MLSA approach for rapid clustering and identification of Genome Groups. The analysis clustered the strains from medicated fish feed, dry foods, and dietary supplements into phylogenetically-related groups. 25-MLSA also pointed to a greater diversity of B. cereus strains from foods and feed than previously recognized. Our integrated approach of toxin gene PCR, and to our knowledge, whole genome sequencing (WGS) based sequence analysis, may be the first of its kind that demonstrates enterotoxigenic potential and genomic diversity in parallel.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2018.06.016DOI Listing
November 2018

Attenuation of inflammatory pain by puerarin in animal model of inflammation through inhibition of pro-inflammatory mediators.

Int Immunopharmacol 2018 Aug 15;61:306-316. Epub 2018 Jun 15.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan; College of Pharmacy, Natural Products Research Institute, Seoul National University, Seoul, Republic of Korea. Electronic address:

In the current study, the puerarin was investigated for both acute Carrageenan and chronic CFA-induced inflammatory pain models. The Puerarin treatment significantly attenuated (P < 0.001) the mechanical hyperalgesia and mechanical allodynia in both Carrageenan and CFA-induced hyperalgesia. The Puerarin treatment also remarkably reduced (p < 0.001) the thermal hyperalgesic responses in both acute Carrageenan as well as chronic CFA-induced models. Furthermore, the Puerarin administration was also associated with significant inhibition of (p < 0.001) paw edema in both Carrageenan and CFA-induced models. The inflammatory mediators such as IL-1β, IL-6, TNF-α and vascular endothelial growth factor (VEGF) are significantly enhanced during inflammatory conditions, however, the Puerarin administration significantly altered (P < 0.001) the mRNA expression levels of these mediators. Additionally, the Puerarin treatment also significantly enhanced (P < 0.001) the mRNA expressions levels of the anti-oxidant enzymes such as Nrf2, HO-1 and SOD2. The Puerarin treatment is associated with significant (P < 0.001) inhibition of the acetic acid-induced Evans blue vascular permeability. Moreover, the concentration of Puerarin in various tissues was analyzed using High-performance liquid chromatography (HPLC) and the results showed that the Puerarin was significantly distributed towards the peripheral tissues such as liver and kidney and less distributed towards the brain.
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http://dx.doi.org/10.1016/j.intimp.2018.05.034DOI Listing
August 2018

Structural confirmation of sulconazole sulfoxide as the primary degradation product of sulconazole nitrate.

J Pharm Anal 2018 Apr 19;8(2):96-102. Epub 2017 Dec 19.

Compendial Development Laboratory, United States Pharmacopeia, Rockville, MD 20852, USA.

Sulconazole has been reported to degrade into sulconazole sulfoxide via sulfur oxidation; however, structural characterization data was lacking and the potential formation of an -oxide or sulfone could not be excluded. To clarify the degradation pathways and incorporate the impurity profile of sulconazole into the () monographs, a multifaceted approach was utilized to confirm the identity of the degradant. The approach combines stress testing of sulconazole nitrate, chemical synthesis of the degradant via a hydrogen peroxide-mediated oxidation reaction, semi-preparative HPLC purification, and structural elucidation by LC-MS/MS and NMR spectroscopy. Structural determination was primarily based on the comparison of spectroscopic data of sulconazole and the oxidative degradant. The mass spectrometric data have revealed a McLafferty-type rearrangement as the characteristic fragmentation pathway for alkyl sulfoxides with a -hydrogen atom, and was used to distinguish the sulfoxide from -oxide or sulfone derivatives. Moreover, the generated sulconazole sulfoxide was utilized as reference material for compendial procedure development and validation, which provides support for USP monograph modernization.
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http://dx.doi.org/10.1016/j.jpha.2017.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5934740PMC
April 2018

Antihyperalgesic Properties of Honokiol in Inflammatory Pain Models by Targeting of NF-κB and Nrf2 Signaling.

Front Pharmacol 2018 20;9:140. Epub 2018 Mar 20.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

The present study investigates the possible anti-nociceptive effect of intraperitoneal (i.p.) honokiol: a phenolic compound originally isolated from , in acute and chronic inflammatory pain models. Doses of 0.1, 5, and 10 mg/kg honokiol were administered in carrageenan induced pain and the dose (honokiol 10 mg/kg i.p.) with most significant response among behavioral tests was selected for further experiments. The i.p. administration of honokiol inhibits mechanical hyperalgesia, mechanical allodynia, and thermal hyperalgesia, without causing any apparent toxicity. To elucidate the effect of honokiol on various cytokines and antioxidant enzymes, quantitative real-time-PCR was performed to determine the expression levels of pro-inflammatory cytokines and antioxidant enzymes. It is demonstrated that honokiol significantly reduced the expression levels of tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF). Similarly, honokiol was also found to potentiate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) levels. Additionally, honokiol significantly reduced plasma nitrite levels as compared to complete Freund's adjuvant (CFA) induced group. X-ray analysis and hematoxylin and eosin (H&E) staining of inflamed and treated paws showed that honokiol reduced the inflammation with significantly less leukocyte infiltration and soft tissue inflammation. In order to explore the possible mechanism of action of honokiol, agonists [piroxicam (5 mg/kg), tramadol (50 mg/kg), and gabapentin (5 mg/kg) i.p.] as well as antagonists [naloxone (4 mg/kg), olanzapine (10 mg/kg), and flumazenil (0.2 mg/kg) i.p.] were used to study involvement of various receptors on the anti-nociceptive effect of honokiol. The potential side effects of honokiol on muscle activity were assessed. An adverse effect testing of honokiol by liver and renal functions were also carried out. The effect of oral honokiol was also assessed on gastrointestinal (GIT) mucosa. Our results demonstrate that honokiol has a significant anti-nociceptive activity through inhibition of anti-inflammatory mediators.
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http://dx.doi.org/10.3389/fphar.2018.00140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5869907PMC
March 2018

Correction to: Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Inflammopharmacology 2018 08;26(4):1139-1140

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Unfortunately, Fig. 1 was incorrectly published in the original publication. The corrected Fig. 1 is given as below.
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http://dx.doi.org/10.1007/s10787-018-0461-5DOI Listing
August 2018

Anti-inflammatory, anti-rheumatic and analgesic activities of 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS) in rodents.

Inflammopharmacology 2018 Aug 22;26(4):1037-1049. Epub 2018 Feb 22.

Department of Pharmacy, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan.

Chronic inflammation is pathologically associated with various clinical conditions such as rheumatoid arthritis. Several anti-inflammatory and analgesic drugs currently available in market presents a wide range of problems. Therefore, the current study was aimed to evaluate anti-inflammatory and analgesic activities of newly synthesized compound 2-(5-mercapto-1,3,4-oxadiazol-2-yl)-N-propylbenzenesulphonamide (MOPBS). Carrageenan and CFA-induced models were developed for evaluation of anti-inflammatory and analgesic activity. Quantitative real-time PCR (qRT-PCR) was performed to determine the mRNA expression levels of inflammatory mediators. Pain behaviours were evaluated by performing Von Frey, Randall Selitto, cold acetone and hot plate test respectively. X-ray imaging and haematoxylin and eosin (H&E) staining were performed for examination of soft tissues of treated mice paw. Additionally, Kodzeila's screen test and weight test were performed for determination of any side effects on motor function and muscle strength. Acute pretreatment of animals with MOPBS (1, 10, 50 and 100 mg/kg, i.p.) produced a significant reduction of paw oedema against carrageenan-induced acute inflammation as well as notable inhibition of mechanical hyperalgesia, allodynia and thermal hyperalgesia. Similarly, in chronic inflammation model, administration of MOPBS (50 mg/kg, i.p.) produced a remarkable reduction of paw oedema. Additionally, MOPBS pretreatment showed a significant inhibition of thermal hyperalgesia, mechanical allodynia, and mechanical hyperalgesia in chronic arthritis model. Several pro-inflammatory mediators such as nitric oxide (NO), vascular endothelial growth factor (VEGF), interleukins (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were inhibited by MOPBS treatment in blood plasma and paw tissues, respectively. MOPBS also enhanced the mRNA expression levels of nuclear factor (erythroid-derived 2)-like 2 (Nrf2), superoxide dismutase (SOD2) and heme oxygenase (HO-1) and in turn reduced arthritis severity and inflammation. Furthermore, anti-inflammatory data were confirmed by X-rays and histological analysis. MOPBS pretreatment did not produce any apparent toxic effect on gastric, kidney and liver function and on muscle strength and motor function. Hence, the present data suggest that MOPBS might be a candidate for several chronic inflammatory diseases such RA and other auto-immune diseases.
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http://dx.doi.org/10.1007/s10787-018-0446-4DOI Listing
August 2018
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