RESUMEN
The swift emergence of antibiotic resistance (AR) in bacterial pathogens to make themselves adaptable to changing environments has become an alarming health issue. To prevent AR infection, many ways can be accomplished such as by decreasing the misuse of antibiotics in human and animal medicine. Among these AR bacterial species, Plesiomonas shigelloides is one of the etiological agents of intestinal infection in humans. It is a gram-negative rod-shaped bacterium that is highly resistant to several classes of antibiotics, and no licensed vaccine against the aforementioned pathogen is available. Hence, substantial efforts are required to screen protective antigens from the pathogen whole genome that can be subjected easily to experimental evaluations. Here, we employed a reverse vaccinology (RV) approach to design a multi-antigenic epitopes based vaccine against P. shigelloides. The complete genomes of P. shigelloides were retrieved from the National Center for Biotechnological Information (NCBI) that on average consist of 5226 proteins. The complete proteomes were subjected to different subtractive proteomics filters, and in the results of that analysis, out of total proteins, 2399 were revealed as non-redundant and 2827 as redundant proteins. The non-redundant proteins were further checked for subcellular localization analysis, in which three were localized in the extracellular matrix, eight were outer membrane, and 13 were found in the periplasmic membrane. All surface localized proteins were found to be virulent. Out of a total of 24 virulent proteins, three proteins (flagellar hook protein (FlgE), hypothetical protein, and TonB-dependent hemoglobin/transferrin/lactoferrin family receptor protein) were considered as potential vaccine targets and subjected to epitopes prediction. The predicted epitopes were further examined for antigenicity, toxicity, and solubility. A total of 10 epitopes were selected (GFKESRAEF, VQVPTEAGQ, KINENGVVV, ENKALSQET, QGYASANDE, RLNPTDSRW, TLDYRLNPT, RVTKKQSDK, GEREGKNRP, RDKKTNQPL). The selected epitopes were linked with each other via specific GPGPG linkers in order to design a multi-epitopes vaccine construct, and linked with cholera toxin B subunit adjuvant to make the designed vaccine construct more efficient in terms of antigenicity. The 3D structure of the vaccine construct was modeled ab initio as no appropriate template was available. Furthermore, molecular docking was carried out to check the interaction affinity of the designed vaccine with major histocompatibility complex (MHC-)I (PDB ID: 1L1Y), MHC-II (1KG0), and toll-like receptor 4 ((TLR-4) (PDB: 4G8A). Molecular dynamic simulation was applied to evaluate the dynamic behavior of vaccine-receptor complexes. Lastly, the binding free energies of the vaccine with receptors were estimated by using MMPB/GBSA methods. All of the aforementioned analyses concluded that the designed vaccine molecule as a good candidate to be used in experimental studies to disclose its immune protective efficacy in animal models.
RESUMEN
OBJECTIVE: Purpose of this study was to find out frequency of anemia and its causes in newly diagnosed treatment naive lymphoma patients. METHODS: We retrospectively studied all lymphoma patients (> 18 years age) diagnosed and treated at Shaukat Khanum Memorial Cancer Hospital and Research Centre, from January 2016 till January 2017. The data was collected from electronic Hospital Information System. Descriptive statistics were done by using summary measures for categorical variables as well as continuous variables. RESULTS: Out of a total 408 patients, 272 were males and 136 females. Median age of patients was 33 years (18-76). Hodgkin lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) were the diagnosis in 201 and 134 patients respectively; rest of the patients had low grade lymphomas. Anemia was present in 184 (45%) patients. Anemia of chronic disease was the commonest cause of anemia and was present in 61 (33.1%) patients. Remaining patients had anemia secondary to marrow involvement 50(27.17%); iron deficiency anemia, Vitamin B-12 deficiency anemia and hemolytic anemia were the causes in 7.6, 1.6%, % and 0.54% respectively. CONCLUSION: Anemia is a common feature in newly diagnosed lymphoma patients with anemia of chronic disease as the commonest cause. It is more frequent in patients with higher stages of lymphoma especially when bone marrow is involved by lymphoma. Since anemia is an important adverse prognostic factor for the outcome of lymphoma patients, work up for anemia prior to initiation of chemotherapy should be done in every lymphoma patient in order to help improve the management of these patients.
RESUMEN
AIM: In the present study quercetin was studied for its role in inflammation, oxidative stress markers and 5-HT levels in unpredictable chronic mild stress (UCMS) animal model of depression. MATERIALS AND METHODS: The mice were randomized into different groups trained for UCMS protocol followed by different drug treatments. Treatments were started after 2 weeks from the start of UCMS protocol and continued up to 6 weeks. The behavioral tests such as modified forced swimming (MFST), tail suspension (TST) and open field tests were performed on week 6, at least 24 h after the last drug treatment. Behavioral tests were preceded following animal sacrifice for biochemical estimations. RESULTS: A significant decrease in swimming, climbing times and increase in immobility time in MFST and TST was observed in UCMS group. Administration of quercetin (25 mg/kg per orally (p.o) reversed these times in MFST and TST. A decrease in no. of field crossing, time spent in centre and no. of rearing were observed in UCMS group. Quercetin reduced these observations in open field test. There was a decrease in superoxide dismutase (SOD), glutathione (GSH), catalase and 5 HT levels in the brain tissue. Quercetin treatment significantly augmented SOD, GSH, catalase and 5 HT levels. Glutamate, TNF-α and IL-6 levels were increased in UCMS group while quercetin decreased these cytokines. CONCLUSION: Quercetin resulted antidepressant-like effect by its antioxidant, anti-inflammatory activities, reduced excitotoxicity and augmented 5 HT levels. This pointed out the usefulness of this phenolic compound as adjuvent drug along with other antidepressant drugs.