Unveiling the Significance of MRP 1 in Achieving Complete Remission Following Induction Therapy in Acute Myeloid Leukemia.

BACKGROUND: Increased expression of MRP 1 in AML patients results in the efflux of drugs from the cells, preventing the patient from achieving remission or potentially leading to relapse. Several studies have demonstrated that early identification of ABC transporter may yield favorable outcomes. AIMS AND OBJECTIVES: The objectives of the study were to investigate the correlation between MRP 1 gene expression and MRP 1 protein levels and the response to remission induction in AML patients. METHOD: A total of 40 AML patients were recruited from March 2021 to June 2022. Peripheral blood was collected in two tubes (yellow and purple top) to assess the MRP 1 gene and protein. For MRP 1 gene assessment, RNA was isolated from blood samples, cDNA was prepared, and qRT-PCR was performed to analyze gene expression. The relationship between the gene and complete remission was determined. Identification of MRP 1 protein was conducted using ELISA, and the relationship between protein levels and complete remission (CR) was explored. RESULTS: Most of the patients were aged between 25 and 39 years, encompassing both males and females. This study observed a clinical correlation between MRP 1 gene expression and complete remission. The findings revealed that 69.2 percent of patients with high gene expression failed to achieve complete remission, whereas the analysis of MRP 1 protein in relation to complete remission showed no statistical significance. The MRP1 gene showed high expression (66.7%) in patients with FLT3 mutation, whereas low expression of MRP1 was associated with a high occurrence (60%) of NMP1 mutation. CONCLUSION: Further comprehensive multicenter studies with larger sample sizes are required to validate the findings of this study. It is recommended to pinpoint the mechanism and regulation of MRP 1 and its interaction with other molecular pathways.

Comparison of efficacy of neoadjuvant chemotherapy with gemcitabine plus cisplatin versus docetaxil, cisplatin, plus fluorouracil in locally advanced nasopharyngeal carcinoma.

Induction followed by concurrent chemoradiation (CCRT) is the standard of care for locally advanced nasopharyngeal carcinoma (LANPC). This study evaluated and compared the efficacy of two regimens of neoadjuvant chemotherapy along with CCRT in LANPC. Patients with LANPC were randomly divided in Group I (receiving neoadjuvant gemcitabine and cisplatin) and Group II (receiving neoadjuvant docetaxil, cisplatin and fluorouracil). Both groups also received concurrent single agent (i.e., cisplatin) chemotherapy and radiotherapy (70Gy). Treatment response was assessed at 8 weeks after the completion of CCRT using RECIST criteria. A total of 68 LANPC patients were enrolled. Group I comprised of 32 patients, with male to female ratio of 2.2, a mean (range, median) age of 38.6±11.3 (19-58, 36) years. Group II comprised of 36 patients, with male to female ratio of 3.5, mean (range, median) age of 40.9 ±11.6 (17-63, 40) years. The complete response was higher whereas the partial response was lower in Group I as compared to Group II (23/32 versus 16/36 and 06/32 versus 18/36, respectively). LANPC patients receiving gemcitabine plus cisplatin based neoadjuvant chemotherapy showed higher response, as compared with docetaxil, cisplatin and fluorouracil based neoadjuvant chemotherapy.

Quality of life of patients undergoing chemotherapy: a tertiary care hospitalbased study from Karachi.

The quality of life (QoL) of cancer patients is of paramount concern due to the enduring effects of chemotherapy on the physical, emotional, spiritual, and social aspects of life. This study aims to examine the factors influencing QoL among cancer patients. A cross-sectional analysis encompassing 200 chemotherapy patients aged 18 and above was conducted, using self-reported surveys and clinical records. The results indicate higher social wellbeing and lower physical well-being scores. Significantly, patients in joint families, with income above Rs25,000, limited pre-diagnosis check-ups, over four chemotherapy cycles, showed better QoL. Engaging diversions like art and internet usage alleviated worries. Conversely, comorbidities correlated with lower FACT-G scores. QoL is still compromised, even with the developments of advanced cancer treatments. Managing mental, emotional, social, and physical health is vital. Future research should focus on evidence-based policies, innovative strategies, psychiatric assessments, mindfulness interventions, and exploring the impact of social interactions on QoL, aiming to enhance the wellbeing of newly diagnosed cancer patients.

Differential analysis of histopathological and genetic markers of cancer aggressiveness, and survival difference in EBV-positive and EBV-negative prostate carcinoma.

Several studies have shown an association between prostate carcinoma (PCa) and Epstein-Barr virus (EBV); however, none of the studies so far have identified the histopathological and genetic markers of cancer aggressiveness associated with EBV in PCa tissues. In this study, we used previously characterized EBV-PCR-positive (n = 39) and EBV-negative (n = 60) PCa tissues to perform an IHC-based assessment of key histopathological and molecular markers of PCa aggressiveness (EMT markers, AR expression, perineural invasion, and lymphocytic infiltration characterization). Additionally, we investigated the differential expression of key oncogenes, EMT-associated genes, and PCa-specific oncomiRs, in EBV-positive and -negative tissues, using the qPCR array. Finally, survival benefit analysis was also performed in EBV-positive and EBV-negative PCa patients. The EBV-positive PCa exhibited a higher percentage (80%) of perineural invasion (PNI) compared to EBV-negative PCa (67.3%) samples. Similarly, a higher lymphocytic infiltration was observed in EBV-LMP1-positive PCa samples. The subset characterization of T and B cell lymphocytic infiltration showed a trend of higher intratumoral and tumor stromal lymphocytic infiltration in EBV-negative tissues compared with EBV-positive tissues. The logistic regression analysis showed that EBV-positive status was associated with decreased odds (OR = 0.07; p-value < 0.019) of CD3 intratumoral lymphocytic infiltration in PCa tissues. The analysis of IHC-based expression patterns of EMT markers showed comparable expression of all EMT markers, except vimentin, which showed higher expression in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Furthermore, gene expression analysis showed a statistically significant difference (p < 0.05) in the expression of CDH1, AR, CHEK-2, CDKN-1B, and CDC-20 and oncomiRs miR-126, miR-152-3p, miR-452, miR-145-3p, miR-196a, miR-183-3p, and miR-146b in EBV-positive PCa tissues compared to EBV-negative PCa tissues. Overall, the survival proportion was comparable in both groups. The presence of EBV in the PCa tissues results in an increased expression of certain oncogenes, oncomiRs, and EMT marker (vimentin) and a decrease in CD3 ITL, which may be associated with the aggressive forms of PCa.

Real-World Challenges of Managing Diffuse Large B-Cell Lymphoma in a Developing Country.

PURPOSE: To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings. MATERIALS AND METHODS: This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines. RESULTS: The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%. CONCLUSION: Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

Mycorrhizosphere bacteria inhibit greenhouse gas emissions from microplastics contaminated soil by regulating soil enzyme activities and microbial community structure.

Microplastics (MPs) accumulation in terrestrial ecosystems can affect greenhouse gases (GHGs) production by altering microbial and soil structure. Presently, research on the MPs effect on plants is not consistent, and underlying molecular mechanisms associated with GHGs are yet unknown. For the first time, we conducted a microcosm study to explore the impact of MPs addition (Raw vs. aged) and Trichoderma longibrachiatum and Bacillus subtilis inoculation (Sole vs. combination) on GHGs emission, soil community structure, physiochemical properties, and enzyme activities. Our results indicated that the addition of aged MPs considerably enhanced the GHGs emissions (N2O (+16%) and CO2 (+21%), respectively), C and N cycling gene expression, microbial biomass carbon, and soil physiochemical properties than raw MPs. However, the soil microbial community structure and enzyme activities were enhanced in raw MPs added treatments, irrespective of the MPs type added to soil. However, microbial inoculation significantly reduced GHGs emission by altering the expression of C and N cycling genes in both types of MPs added treatments. The soil microbial community structure, enzymes activities, physiochemical properties and microbial biomass carbon were enhanced in the presence of microbial inoculation in both type of MPs. Among sole and combined inoculation of Trichoderma and Bacillus subtilis, the co-applied Trichoderma and Bacillus subtilis considerably reduced the GHGs emission (N2O (-64%) and CO2 (-61%), respectively) by altering the expression of C and N cycling genes regardless of MPs type used. The combined inoculation also enhanced soil enzyme activities, microbial community structure, physiochemical properties and microbial biomass carbon in both types of MPs treatment. Our findings provide evidence that polyethylene MPs likely pose a high risk of GHGs emission while combined application of Trichoderma and Bacillus subtilis significantly reduced GHGs emission by altering C and N cycling gene expression, soil microbial community structure, and enzyme activities under MPs pollution in a terrestrial ecosystem.

Metal-tolerant morganella morganii isolates can potentially mediate nickel stress tolerance in Arabidopsis by upregulating antioxidative enzyme activities.

Plant growth-promoting rhizobacteria (PGPRs) have been utilized to immobilize heavy metals, limiting their translocation in metal contaminated settings. However, studies on the mechanisms and interactions that elucidate how PGPRs mediate Nickel (Ni) tolerance in plants are rare. Thus, in this study we investigated how two pre-characterized heavy metal tolerant isolates of Morganella morganii (ABT9 and ABT3) improve Ni stress tolerance in Arabidopsis while enhancing its growth and yield. Arabidopsis seedlings were grown for five weeks in control/Ni contaminated (control, 1.5 mM and 2.5 mM) potted soil, in the presence or absence of PGPRs. Plant growth characteristics, quantum yield, and antioxidative enzymatic activities were analyzed to assess the influence of PGPRs on plant physiology. Oxidative stress tolerance was quantified by measuring MDA accumulation in Arabidopsis plants. As expected, Ni stress substantially reduced plant growth (shoot and root fresh weight by 53.25% and 58.77%, dry weight by 49.80% and 57.41% and length by 47.16% and 64.63% over control), chlorophyll content and quantum yield (by 40.21% and 54.37% over control). It also increased MDA content by 84.28% at higher (2.5 mM) Ni concentrations. In contrast, inoculation with M. morganii led to significant improvements in leaf chlorophyll, quantum yield, and Arabidopsis biomass production. The mitigation of adverse effects of Ni stress on biomass observed in M. morganii-inoculated plants was attributed to the enhancement of antioxidative enzyme activities compared to Ni-treated plants. This upregulation of the antioxidative defense mechanism mitigated Ni-induced oxidative stress, leading to improved performance of the photosynthetic machinery, which, in turn, enhanced chlorophyll content and quantum yield. Understanding the underlying mechanisms of these tolerance-inducing processes will help to complete the picture of PGPRs-mediated defense signaling. Thus, it suggests that M. morganii PGPRs candidate can potentially be utilized for plant growth promotion by reducing oxidative stress via upregulating antioxidant defense systems in Ni-contaminated soils and reducing Ni metal uptake.

Epidemiological and clinical characteristics of esophageal carcinoma: An experience from tertiary care hospital of Karachi, Pakistan.

Objectives: To describe current trends and characteristics of esophageal cancer (EC) over the past ten years largest tertiary care hospital of Karachi, Pakistan. Methods: This single center retrospective study was conducted at the Department of Gastroenterology and Oncology, Jinnah Postgraduate Medical Center, Karachi, Pakistan, between the period of ten years from 1st January 2010 to 31st December 2019. Patient data including epidemiological characteristics such as age, gender, education, residence, occupation, addictions, comorbidities, symptoms, location of EC, laboratory parameters and histopathological type were recorded. All patients with missing histological and radiological findings were excluded. Results: The mean age of all patients was 49.26±14.24 years and among them majority were females 566 (56.1%). Almost, 834 (82.7%) patients had SQC and 175 (17.3%) presented with ADS. Most common presenting symptom was dysphagia in both groups 327 (32.4%) followed by vomiting (22.8%) and weight loss 196 (19.4%). The Esophagogastroduodenoscopy (EGD) findings showed the distal esophagus involvement in most of the patients (36.3%) in both groups. CT scan findings showed that the lower region was the most involved region in 367 (36.4%) patients, followed by middle and upper in 227 (22.5%) and 156 (15.5%) patients respectively. The thickening of mass on CT- scan was circumferential in most of the patients (42.7%) in both groups. Conclusion: According to our findings, SQC is more prevalent than ADC. Female predominance especially at younger age was most common as compared to past studies. No significant association between a single risk factor has been found in our study however smoking and betel nut chewing were found as known putative risk factors.

Heavy metal-resistant rhizobacteria fosters to alleviate the cadmium toxicity in Arabidopsis by upregulating the plant physiological responses.

This study was designed to investigate the role of Morganella morganii strains in alleviating Cd stress in Arabidopsis seedlings under controlled conditions. Both M. morganii strains ABT3 (ON316873) and ABT9 (ON316874) strains isolated from salt-affected areas showed higher resistance against Cd and possess plant growth-promoting traits such as nitrogen fixation, indole-acetic acid production, ammonia production, phosphate solubilization, and, catalase, gelatinase and protease enzyme production. Plant inoculation assay showed that varying concentration of Cd (1.5 mM and 2.5 mM) significantly reduced Arabidopsis growth, quantum yield (56.70%-66.49%), and chlorophyll content (31.90%-42.70%). Cd toxicity also triggered different associations between lipid peroxidation (43.61%-69.77%) and enzymatic antioxidant mechanisms. However, when both strains were applied to the Arabidopsis seedlings, the shoot and root length and fresh and dry weights were improved in the control and Cd-stressed plants. Moreover, both strains enhanced the resistance against Cd stress by increasing antioxidant enzyme activities [catalase (19.47%-27.39%) and peroxidase (37.50%-48.07%)]that ultimately cause a substantial reduction in lipid peroxidation (27.71%-41.90%). Both strains particularly ABT3 also showed positive results in improving quantum yield (73.84%-98.64%) and chlorophyll content (41.13%-48.63%), thus increasing the growth of Arabidopsis seedlings. The study suggests that PGPR can protect plants from Cd toxicity, and Cd-tolerant rhizobacterial strains can remediate heavy metal polluted sites and improve plant growth.

In order to develop sustainable and effective agricultural techniques in areas polluted with heavy metals, it is important to have a deeper understanding of the characteristics of metal-resistant PGPR. Hence, this study focuses on the efficacy of M. morganii in promoting the growth and increasing the photosynthetic pigments of Arabidopsis seedlings under Cd toxicity.

Acidified manure and nitrogen-enriched biochar showed short-term agronomic benefits on cotton-wheat cropping systems under alkaline arid field conditions.

Application of organic residues such as farm manure and biochar in various agricultural environments have shown positive effects on soil carbon sequestration. However, there is a lack of consensus regarding the agronomical benefits of a single and small dose of biochar and farm manure in arid alkaline soils. Therefore, a field experiment with the given treatments (1) control (no amendment), (2) acidified manure (AM) at 300 kg ha-1, (3) nitrogen (N) enriched biochar (NeB) at 3 Mg ha-1, and (4) an equal combination of AM + NeB (150 kg ha-1 AM + 1.5 Mg ha-1 NeB)) was conducted in a typical cotton-wheat cropping system. A parallel laboratory incubation study with the same amendments was carried out to account for soil carbon dioxide emission (CO2). The N enrichment of biochar and its co-application with acidified manure increased soil mineral N (NO3- and NH4+) in the topsoil (0-15 cm), and increased total N uptake (25.92% to 69.91%) in cotton over control, thus reducing N losses and increased uptake over control. Compared to the control, co-application of AM + NeB significantly improved soil N and P bioavailability, leading to increased plant biomass N, P, and K (32%, 40%, 6%, respectively) uptake over control. The plant's physiological and growth improvements [chlorophyll (+ 28.2%), height (+ 47%), leaf area (+ 17%), number of bolls (+ 7%), and average boll weight (+ 8%)] increased the agronomic yield in the first-season crop cotton by 25%. However, no positive response was observed in the second season wheat crop. This field study improved our understanding that co-application of acidified manure and N-enriched biochar in small dose can be a strategy to achieve short-term agronomic benefits and carbon sequestration in the long run.

Unsteady Ohmic dissipative flow of ZnO-SAE50 nanofluid past a permeable shrinking cylinder.

The laminar boundary layer flow of a Zinc Oxide-Society of Automotive Engineers 50 alias nano-lubricant (ZnO-SAE50) past a permeable shrinking cylinder is investigated. The flow is unsteady, incompressible, and Ohmic dissipative. The present study holds immense significance in different engineering as well as scientific domains. It combines research on nanoparticle effects, unsteady flows, and solid surface interactions. The study claimed that the use ofZnO-SAE50nanofluid in the unsteady flow past a permeable shrinking cylinder led to significant heat transfer enhancement. The acquired results from the study would be fruitful in the fields of thermal engineering and heat transfer. The findings of the study can aid in optimizing cooling systems, heat exchangers, and energy-efficient designs. A governing model has been achieved for the flow and heat transfer by using conservation laws related to mass, momentum, and energy. Governing system of partial differential equations is solved to a nonlinear system of ordinary differential equations by using similarity transformation, which is later on solved with the help of the Shooting method and RK-Fehlberg duos. Plots are shown for both velocity and temperature profiles, to display the impacts of involved dimensionless parameters. Additionally, graphs for Nusselt Number have also been represented which shows the local rate of heat transfer. It is examined that the Ohmic dissipation as well as the volumetric ratio of the nanoparticles greatly influence the overall thermal performance of the system.

Microplastics drive microbial assembly, their interactions, and metagenomic functions in two soils with distinct pH and heavy metal availability.

Microplastics (MPs) have emerged as widely existing global environmental concerns in terrestrial ecosystems. However, the mechanisms that how MPs are affecting soil microbes and their metagenomic functioning is currently uncertain. Herein, we investigated the response mechanisms of bacterial and fungal communities as well as the metagenomic functions to the addition of MPs in two soils with distinct pH and heavy metals. In this study, the acidic soil (Xintong) and the neutral soil (Huanshan) contaminated by heavy metals were incubated with Polyvinyl Chloride (PVC) MPs at ratios of 2.5% and 5% on 60 and 120 days. We aimed to evaluate the responding, assembly, and interactions of the metagenomic taxonomy and function. Results showed that only in the acidic soil, PVC MPs significantly increased soil pH and decreased CaCl2-extractable heavy metals, and also reduced bacterial alpha diversity and interaction networks. The relative proportions of Proteobacteria and Bacteroidota in bacteria, and Mortierellomycota in fungi, were increased, but Chloroflexi and Acidobacteriota in bacteria, Ascomycota and Basidiomycota in fungi, were significantly decreased by PVC MPs. Metagenomic functions related to C cycling were repressed but the nutrient cycles were enriched with PVC MPs. In conclusion, our study suggests that the addition of PVC MPs could shift soil microbial community and metagenomic functioning, as well as increasing soil pH and reduced heavy metal availability.

Karachi Cancer Registry (KCR): Consolidated Data of 5-years 2017-2021.

OBJECTIVE:  To collect and analyse epidemiologic data of all malignancies by age group and gender for the Karachi population to estimate the cancer incidence of 5-years (2017-2021) and identify major risk factors for setting priorities towards cancer control programs. STUDY DESIGN: Observational study. Place and Duration of the Study: Karachi Cancer Registry (KCR) Secretariat, Pakistan Health Research Council (PHRC), JPMC, Karachi, from 2017-2021. METHODOLOGY: Cancer data of seven tertiary care hospitals of Karachi submitted to KCR during the study period were analysed including age, gender, date of first contact, primary site and ICD coding. All the data was cleaned, merged, and analysed. All patients 0-14 years were classified as 'children', all aged 15-19 years were classified as 'adolescents', and those age 20-years and above as 'adults'. Age standardised incidence rates (ASIR) were determined for both genders. RESULTS: During the last five years (2017-2021), a total of 65,886 malignant cases were received. The distributions seen amongst males and females were 33,510 (51%) and 32,376 (49%), respectively with 60,145 (91.3%) tumours found in adults (≥20 years), 4844 (7.3%) in children, and 897 (1.4%) in adolescents. The three most common tumour sites were oral, liver, and colorectal in males; breast, oral and ovary in females; bone, brain and connective tissue in adolescents; and leukaemia, brain and bone in children. The overall ASIR (%) in males was 89.20 for adults, 9.19 for children, and 1.61 for adolescents. The overall ASIR (%) in females was 93.44 for adults, 5.45 for children, and 1.11 for adolescents. CONCLUSION: Oral cancer, a largely preventable cancer is the leading cancer in males while breast cancer is the leading cancer in females followed by oral cancer. In adolescents and children, the incidence closely matches most of the world. KEY WORDS: Karachi, Cancer registry, Oral cancer, Breast cancer, Age-standerdised ratio.

Biochar alleviated the toxic effects of PVC microplastic in a soil-plant system by upregulating soil enzyme activities and microbial abundance.

Plastics have become an emerging pollutant threatening the sustainability of agroecosystems and global food security. Biochar, a pro-ecosystem/negative carbon emission technology can be exploited as a circular approach for the conservation of plastics contaminated agricultural soils. However, relatively few studies have focused on the effects of biochar on plant growth and soil biochemical properties in a microplastic contaminated soil. This study investigated the effects of a cotton stalk (Gossypium hirsutum L.) biochar on plant growth, soil microbes, and enzyme activity in PVC microplastic (PVC-MPs) contaminated soil. Biochar amendment increased shoot dry matter production in PVC-MPs contaminated soil. However, PVC-MPs alone significantly reduced the soil urease and dehydrogenase activity, soil organic and microbial biomass carbon, bacterial/fungal community percentage, and their abundance (16S rRNA and 18S rRNA genes, respectively). Interestingly, biochar amendment with PVC-MPs significantly alleviated the hazardous effects. Principal component and redundancy analysis of the soil properties, bacterial 16S rRNA genes, and fungal ITS in the biochar-amended PVC-MPs treatments revealed that the observed traits formed an obvious cluster compared to non-biochar treatments. To sum up, this study indicated that PVC-MPs contamination was not benign, while biochar shielded the hazardous effects and sustained soil microbial functionality.

Polymorphic Variants of ASS1 Gene Related to Arginine Metabolism and the Risk of HCC.

BACKGROUND: Hepatocellular carcinoma is a primary liver cancer and 6th most common cancer globally. Inefficient diagnostic strategies and the limited availability of treatments are the foremost reasons. Variable factors directly impact the disease burden, among them, molecular alterations have been found to play a significant role. In liver, argininosuccinate synthase-1 is a center of arginine metabolism and rate limiting enzyme of urea cycle. It also triggers multiple mechanisms that lead to HCC pathogenesis. OBJECTIVES: The aim of this study is to analyze the ASS1 gene expression, its polymorphic genotype and microsatellite instability among HCC patients from our Pakistani population. METHOD: Blood samples were collected from disease and healthy control individuals. Allele-Specific PCR was performed for SNP analysis. MSI of tri and tetra nucleotide repeats were analyzed by PCR. The differential expression of ASS1 gene was also investigated. Furthermore, the reactome database and STRING software were utilized for finding correlations between ASS1 gene with other associated gene/proteins. RESULTS: The GG wild-type genotype was more prevailed in the disease group as compared to the control. Significant downregulation in ASS1 and NOS2 genes was observed. Bioinformatics analysis reveals the correlation between ASS1 polymorphism and HCC development appears to be linked with the EMT pathway and polyamine production. Furthermore, MSI significantly resided in the disease group. Results were analyzed statistically to calculate the significance of obtained results. CONCLUSION: Study concludes that the insight of HCC mechanism through population-specific genetic mutations and altered gene expression of ASS1 might be helpful in early diagnostic and therapeutic purposes.

Association of Kaiso and partner proteins in oral squamous cell carcinoma.

Objectives: 1. Identification of protein expression and subcellular localization of E-cadherin (E-cad), p120 catenin (P120ctn), and Kaiso in oral cancer (OC). 2. To study the protein expression of cyclin D1 and c-Myc (Kaiso targets) and determine their relationship with the expression and localization of Kaiso. Methods: Histological grading was performed in accordance with Broder's criteria. Expression and localization data for E-cad, p120ctn, Kaiso, cyclin D1, and c-Myc were acquired using immunohistochemistry. Data were analyzed using SPSS version 21. The chi-square test was used to measure the statistical significance of associations, with p < 0.05 as statistically significant. Results: Of 47 OC cases, 36% showed low E-cad expression and 34% showed low p120ctn. Low Kaiso expression was recognized in 78% of tumor specimens. Aberrant cytoplasmic localization of p120ctn was seen in 80.8% cases. Cytoplasmic Kaiso localization was appreciated in 87% of tumor tissues, whereas 29.7% lacked any nuclear Kaiso. Kaiso expression was significantly associated with the expression of cyclin D1 but not with c-Myc. Conclusion: The present study identified a change in the localization of Kaiso in OC. The significance of this in relation to OC and tumor prognosis needs to be investigated with further studies using larger sample sizes and more sensitive molecular tools.

Microplastics alter soil enzyme activities and microbial community structure without negatively affecting plant growth in an agroecosystem.

Despite the enormous benefits that plastics bring to our daily lives, plastics accumulate in the environment, especially microplastics (MPs; defined as particles <5 mm), which can cause many problems and potential loss of ecosystem services. Current research has shown the significant impact of MPs on aquatic systems, but little is known about their effect on terrestrial systems, especially within agroecosystems. Here, we investigated the effect of MPs types (PS, PE and PVC) on plant growth, soil enzyme activities, and microbial communities. MPs had a positive, type-dependent influence on plant growth affecting both above and below-ground productivity. MPs, especially PVC increased dry weights (+69.51 and + 164.62), and root length (+54.81) relative to control. Although the activity of ß-glucosidase, alkaline phosphatase, cellobiohydrolase, leucine-aminopeptidase, and dehydrogenase was suppressed by MPs except urease activity which was enhanced by MPs addition. The type of MPs in soil significantly altered C flow through the soil-plant system, indicating that MPs adversely affect many C-dependent soil functions. However, MPs (especially PVC) enhanced microbial biomass carbon (+14.88%) and altered the structure and metabolic status of the microbial community. MPs addition (especially PVC) greatly enhanced soil microbial structure (+29.59%; indicated by PLFAs) compared to control. Here we provide evidence that MPs can have significant effects on key pools and fluxes within the terrestrial C cycle, with responses being MPs type-dependent. Therefore, we concluded that MPs in soil are not benign and every step should be taken to restrict their access to the soil-plant system and their potential to transfer into the food chain.

Different feedstocks of biochar affected the bioavailability and uptake of heavy metals by wheat (Triticum aestivum L.) plants grown in metal contaminated soil.

Heavy metals (HMs) contamination of agricultural soils is an emerging food safety challenge at world level. Therefore, as a possible treatment for the remediation of a HMs contaminated soil (sewage water irrigation for 20-years), the impact of biochar (BC) was investigated on the uptake of HMs by wheat (Triticum aestivum L.) plants. The BC was produced from seven different feedstocks (cotton stalks (CSBC), rice straw (RSBC), poultry manure (PMBC), lawn grass (LGBC), vegetable peels (VPBC), maize straw (MSBC), and rice husks (RHBC)). Each BC was applied at 1.25% (dry weight basis, w/w) in contaminated soil and a control was maintained without BC addition and wheat was grown in potted soil and harvested at maturity. Results revealed that the properties of different biochars regulated their effects on soil nutrient and HMs mobility and uptake by plants. The maximum plant phosphorous and potassium uptake and translocation to grain (173.4% and 341%, respectively) was found in RSBC treatment over control. The RHBC, PMBC, and MSBC treatments showed a maximum decrease in grain Cd concentration (32.9%, 33.8%, and 34.1%, respectively) compared to the control. The grain Pb (-41% to -51%, with no significant differences among different treatments) and Ni (-63%) concentrations were also reduced significantly following BC treatments compared to control. The daily intake and health risk index of Cd were significantly decreased due to PMBC (-28.1% and -33.8%, respectively), and MSBC (-28.3% and -34.1%, respectively) treatment over control. The BC treatments significantly increased the translocation factor of Cd in the order of VPBC (52.1%) > LGBC (25.4%) > CSBC (13.6%) > RSBC (12.1%) compared to control. The study demonstrated that the effects of BC on metal uptake in plants varied with feedstocks and suitable BC can be further exploited for the rehabilitation of contaminated soils and thereby ensuring food safety.

Significance of ca15-3 in carcinoma of the breast with Visceral metastases.

Background: The most common malignancy and second most common cause of death is breast cancer among women. About 2.09 million fatalities from breast cancer happened in 2018. The objective was to evaluate the elevated CA15-3 in breast cancer patients with visceral metastases presenting at the tertiary care hospital of Karachi. Methods: It was a cross-sectional study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from 15th December 2018 to 15th November 2019. Female patients aged 26-80 years diagnosed with visceral metastatic (defined as metastasis to lung, liver, brain and adrenal glands) breast cancer were included in the study. The diagnosis of breast cancer was confirmed on histopathology whereas the metastatic sites were evaluated using physical examination and imaging. The serum CA15-3 concentration was assessed using assay kits. The serum CA15-3 level of 0-32 U/ml was taken as normal range for all the patients whereas CA15-3 level greater than 32 U/L was considered as elevated CA15-3. SPSS version 23 was used to enter and analyze data. Results: A total of 139 females were included in the study. The mean age & BMI of the patients were reported as 46.5 years & 26.69 kg/m2. In the majority of the patients' metastases were detected in the liver (n=54), 92 in the lungs+ parenchymal disease, 20 in adrenal glands, 12 in pleural effusion and 10 in the brain. Out of 139 patients with visceral metastases, 52(37.4%) had normal CA15-3 level whereas 87 (62.6%) had elevated serum CA15-3 levels (>32 U/L). Conclusion: The serum CA15-3 tumour marker is elevated significantly in visceral metastases and can be used as a prognostic marker in metastatic breast cancer patients.

Effect Of Tamoxifen On Plasma Lipid Profile In Patients Of Breast Cancer.

BACKGROUND: To evaluate the effect of Tamoxifen on plasma lipid profile in breast cancer patients presenting at tertiary care hospitals. METHODS: It was a longitudinal study conducted at the Department of Oncology of Jinnah Postgraduate Medical Center from December 2018 to November 2019. Eighty-eight females aged 26-66 years diagnosed with breast cancer were included in the study using a non-probability consecutive sampling technique. Detailed gynaecological and clinical investigations and detailed history were taken. The blood samples of all the patients were collected and the plasma lipid profile was measured before initiation of Tamoxifen treatment and three- and six-months post-treatment at the clinical laboratory. The plasma lipid profile includes the measurement of Total cholesterol (mg/dl), Triglyceride(mg/dl), High-density Lipoprotein (mg/dl) & Low-density Lipoprotein (mg/dl). SPSS version 23 was used to analyse data. RESULTS: After treatment, there was a significant reduction in serum cholesterol & Low-density Lipoprotein level by 20.54 mg/dl & 16.46 mg/dl at 3 months (p<0.05), moreover there was a significant increase in Triglyceride by 22.14 at 3 months (p<0.05). No significant difference was observed in High density lipoprotein level at 3 months after using Tamoxifen. At 6 months there was a significant reduction in serum cholesterol and low-density lipoprotein by 32.29mg/dl and 24.11 mg/dl at 6 months (p<0.05), moreover there was a significant increase in Triglyceride level by 42.19 mg/dl at 6 months (p<0.05). No significant difference was observed in High-density lipoprotein level at 6 months after using Tamoxifen. CONCLUSIONS: Total cholesterol and Low-density Lipoprotein levels showed significant reduction over the period of six months from the baseline with the use of Tamoxifen. Hence Tamoxifen should be considered to have an added advantage on lipid metabolism and therefore, can reduce the risk of cardiovascular events.