BackgroundChronic kidney disease (CKD) is a group of heterogeneous abnormalities affecting the function and structure of the kidney and mostly further proceeds to cardiovascular damage prior to end stage renal disease (ESRD). The oxidative insult and inflammatory mediators have some undefined role in CKD and cardiovascular complications. It is therefore, aimed at to pin point the predictive factors in the development of cardiovascular disorder in patients with chronic kidney disease.MethodsFifty patients of CKD experiencing cardiovascular distress and twenty normal individuals having same age and sex acted as control during these observations. Blood samples (Each 5 ml) were drawn and subjected to centrifugation for 10–15 minutes to separate the serum at 4000-5000rpm. The levels of MDA, GSH, SOD, CAT, VIT C, VIT E, IL-1, TNF-alpha, nitric oxide (NO) and advanced oxidation protein products (AOPPs) were estimated and analyzed.ResultsThe nitric oxide levels in the CKD patients decreased significantly (13.26±1.25 ng/ml) compared to controls (42.15±5.26 ng/ml). The serum vitamin E and C levels in these patients recorded 2.15±0.25 μg/ml and 0.97±0.09 μg/ml respectively as against their assigned controls which read 6.35±1.22 μg/ml and 3.29±0.25 μg/ml. Furthermore, a significantly higher level of Malondialdehyde (MDA) as1.25±0.07 nmol/ml was observed in CKD patients viz-a-viz relevant control. However, the serum SOD, catalase (CAT) and GSH levels in the same patients registered a significant decline as evident from respective figures 0.07±0.002 μg/dl, 1.22±0.012 μmol/mol, and 3.25±1.05 μg/dl. The control for these was observed as0.99±0.06 μg/dl, 3.19±0.05 μmol/mol, and 8.64±0.03 μg/dL. On the other hand, the IL-1 levels in the CKD patients found quite higher (402.5±18.26 pg/ml). This clearly points to substantial increase in oxidative insult and reduced NO levels leading to the renal and cardiovascular damage.ConclusionObservations support the fact that the decrease in anti-oxidative capacity accompanied by higher inflammatory mediators in CKD is indicative of oxidative stress, consequently leading to CKD progression, in all probability to cardiovascular insult. The outcome reiterates that strategies be designed afresh to contain CKD progression to cardiovascular complications and ESRD. One way could be to focus on early detection of stress related to the disease. It requires analyzing the factors related to stress, such as the one reported here. Linking these factors with the symptoms could be a crucial step forward. And further, the disease could be monitored in a more disciplined manner.
Hard ticks (Ixodidae: Acari) are haematophagous ectoparasites of vertebrates (e.g. mammals, birds, reptiles and amphibians) and transmit diverse viral, bacterial and protozoan pathogens to their hosts (Dantas-Torres, 2015). The transmission of tick-borne diseases to humans (i.e. zoonosis) is one of the world's most significant public health issues. In horses, ticks spread several infectious diseases (Dantas-Torres, 2015; Karim et al., 2017) such as papulonodular dermatoses, lyme disease and viral encephalitis, which have serious detrimental consequences (Conway et al., 2014; Divers et al., 2018). They can also cause parasite-induced abortion (Walker et al., 2002). Several tick species require more than one vertebrate host for the completion of immature and mature developmental stages in their life cycles. At the adult stage, ticks exhibit host-specific preference (McCoy et al., 2013), which can be influenced by its biological parameters such as parasitic phase, reproductive performance (Amaral et al., 2012) and environmental variables (biotic and abiotic) such as seasonality and temporal distribution (MacDonald et al., 2019). In such conditions, seasonal variation that causes changes in temperature, types of vegetation and availability of hosts may influence the survival, reproduction rate and host-finding behaviour of different tick species (Keirans et al., 1996). All these factors have been shown ultimately to influence the probability that ticks will transmit pathogenic agents (Nava & Guglielmone, 2013; Alonso-Carné et al., 2016). The current projections of climate change that will be caused due to anthropogenic changes suggest that these zoonotic problems may be intensified and different regions of the world may become
BackgroundOvarian cancer is the 5th most common cause of deaths in the women among gynecological tumors. There are many growing evidences that stress and other behavioral factors may affect cancer progression and patient survival. The purpose of this study is to determine the key role of matrix metalloproteinases (MMPs), and cytokines in the aggregation and progression of ovarian cancer.MethodologyStress variables (MDA, AGEs, AOPPs, NO), profile of antioxidants (SOD, Catalase, Vitamin E & A, GSH, GRx, GPx) and inflammatory biomarkers (MMP-9, MMP-2, MMP-11, IL-1α and TNF-α) were biochemically assessed from venous blood of fifty ovarian cancer patients and twenty healthy control subjects. The results of all parameters were analyzed statistically by independent sample t-test.ResultsThe results of the study demonstrated that the levels of stress variables like MDA (3.38±1.12nmol/ml), AGEs (2.72±0.22 ng/ml), AOPPs (128.48±27.23 ng/ml) and NO (58.71±8.67 ng/ml) were increased in the patients of ovarian cancer as compared to control individuals whereas the profile of antioxidants like SOD, Catalase, Vitamin E, Vitamin A, GSH and GRx were decreased in ovarian cancer patients (0.11±0.08 μg/ml, 2.41±1.01μmol/mol of protein, 0.22±0.04 μg/ml, 45.84±9.07μg/ml, 4.88±1.18μg/ml, 5.33±1.26 μmol/ml respectively). But the level of GPx antioxidant was increased in ovarian cancer patients (6.58±0.21μmol/ml). Moreover the levels of MMP-9 (64.87±5.35 ng/ml), MMP-2 (75.87±18.82 ng/ml) and MMP-11 (63.58±8.48 ng/ml) were elevated in the patients. Similarly, the levels of various cytokines TNF-α and IL-1α were also increased in the patients of ovarian cancer (32.17±3.52 pg/ml and 7.04±0.85 pg/ml respectively).ConclusionMMPs are commonly expressed in ovarian cancer which are potential extrapolative biomarkers and have a major role in metastasis. Due to oxidative stress, different cytokines are released by tumor associated macrophages (TAMs) that result in the cancer progression. Consequently, tissue inhibitors of matrix metalloproteinases (TIMPs) are the valuable therapeutic approaches to complement conservative anticancer strategies.
The world is currently gripped by the fear of the corona virus disease 2019 (COVID-19) pandemic. The causative agent of COVID-19 is a novel coronavirus known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that attacks humans without prejudice, and primarily targets the respiratory system. Pakistan is a developing country with a large population and a weak economy. Currently, it is facing a major challenge to cope with the outbreak of the COVID-19 pandemic, especially the third wave. This fatal virus has increased its presence many folds in Pakistan. On average, 100 deaths per day were being recorded in the late spring of 2021. Delay in the acquisition of vaccine has slowed down the vaccination program for this disease. This in turn will accelerate the spreading of virus, and thus will lead to a lockdown situation.
Philadelphia (Ph) chromosome (9;22)(q34;q11) is well established in more than 90% of chronic myeloid leukemia (CML) patients, and the remaining 5–8% of CML patients show variant and complex translocations, with the involvement of third, fourth, or fifth chromosome other than 9;22. However, in very rare cases, the fourth chromosome is involved. Here, we found a novel case of four-way Ph+ chromosome translocation involving 46,XY,t(4;9;19;22)(q25:q34;p13.3;q11.2) with CML in the chronic phase. Complete blood cell count of the CML patient was carried out to obtain total leukocytes count, hemoglobin, and platelets. Fluorescence in situ hybridization technique was used for the identification of BCR–ABL fusion gene, and cytogenetic test for the confirmation of Ph (9;22)(q34;q11) and the mechanism of variant translocation in the bone marrow. The patient is successfully treated with a dose of 400 mg/day imatinib mesylate (Gleevec). We observed a significant decrease in white blood cell count of 11.7 × 109/L after 48-month follow-up. Patient started feeling better generally. There was a reduction in the swelling of the body, fatigue, and anxiety.
Ticks (Acari; Ixodidae) are the second most important vector for transmission of pathogens to humans, livestock, and wildlife. Ticks as vectors for viruses have been reported many times over the last 100 years. Tick-borne viruses (TBVs) belong to two orders (Bunyavirales and Mononegavirales) containing nine families (Bunyaviridae, Rhabdoviridae, Asfarviridae, Orthomyxovirida, Reoviridae, Flaviviridae, Phenuviridae, Nyamiviridae, and Nairoviridae). Among these TBVs, some are very pathogenic, causing huge mortality, and hence, deserve to be covered under the umbrella of one health. About 38 viral species are being transmitted by <10% of the tick species of the families Ixodidae and Argasidae. All TBVs are RNA viruses except for the African swine fever virus from the family Asfarviridae. Tick-borne viral diseases have also been classified as an emerging threat to public health and animals, especially in resource-poor communities of the developing world. Tick-host interaction plays an important role in the successful transmission of pathogens. The ticks' salivary glands are the main cellular machinery involved in the uptake, settlement, and multiplication of viruses, which are required for successful transmission into the final host. Furthermore, tick saliva also participates as an augmenting tool during the physiological process of transmission. Tick saliva is an important key element in the successful transmission of pathogens and contains different antimicrobial proteins, e.g., defensin, serine, proteases, and cement protein, which are key players in tick-virus interaction. While tick-virus interaction is a crucial factor in the propagation of tick-borne viral diseases, other factors (physiological, immunological, and gut flora) are also involved. Some immunological factors, e.g., toll-like receptors, scavenger receptors, Janus-kinase (JAK-STAT) pathway, and immunodeficiency (IMD) pathway are involved in tick-virus interaction by helping in virus assembly and acting to increase transmission. Ticks also harbor some endogenous viruses as internal microbial faunas, which also play a significant role in tick-virus interaction. Studies focusing on tick saliva and its role in pathogen transmission, tick feeding, and control of ticks using functional genomics all point toward solutions to this emerging threat. Information regarding tick-virus interaction is somewhat lacking; however, this information is necessary for a complete understanding of transmission TBVs and their persistence in nature. This review encompasses insight into the ecology and vectorial capacity of tick vectors, as well as our current understanding of the predisposing, enabling, precipitating, and reinforcing factors that influence TBV epidemics. The review explores the cellular, biochemical, and immunological tools which ensure and augment successful evading of the ticks' defense systems and transmission of the viruses to the final hosts at the virus-vector interface. The role of functional genomics, proteomics, and metabolomics in profiling tick-virus interaction is also discussed. This review is an initial attempt to comprehensively elaborate on the epidemiological determinants of TBVs with a focus on intra-vector physiological processes involved in the successful execution of the docking, uptake, settlement, replication, and transmission processes of arboviruses. This adds valuable data to the existing bank of knowledge for global stakeholders, policymakers, and the scientific community working to devise appropriate strategies to control ticks and TBVs.
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