Hypo-Albuminemia and Perioperative Renal Transplant-Related Infections: A Systematic Review and Meta-Analysis.

OBJECTIVE: to review the literature regarding the relationship between pre- and post-transplant hypo-Albuminemia with various renal transplant-related infections. MATERIALS AND METHODS: In a systematic review, we included the following keyword in the search: (Albumin*) AND (infection*) AND ("renal transplant" OR "renal transplantation" OR "renal transplants") OR ("kidney transplant" OR "kidney transplantation" OR "kidney transplants") OR "kidney grafting") with investigating databases including ProQuest, PubMed, Scopus, and Web of Science to May 2023. All adult patients who had renal transplantation were included. Albumin levels of infected (bacterial, fungal, or viral) patients and the type of infection should be reported in the included studies. The search strategy used in this review was reported by Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension (PRISMA-S). To conduct Meta-analyses, Stata version 17 was used. Also, DerSimonian-Laird random-effects models were used for this study. In our study, heterogeneity was quantified with I2 and τ2 statistics. inconsistency across studies is quantified by I2 statistics, and the impact of heterogeneity on the meta-analysis is assessed by this quantification. RESULTS: Overall, 18 studies were found to be reporting measures of association including risk ratio, odds ratio, and, hazard ratio. Among them, 10 and 8 studies were reporting bacterial and viral types of infection. The combined risk ratios were not statistically significant, in either type of infection. The mean (SD) of ages for bacterial and viral infections were found to be 45.3 (6.4) and 50.5 (7.6) years old, respectively. CONCLUSION: Hypoalbuminemia is not related to post-transplantation infections, and it seems that with adherence to proper pretransplant screening of recipients, vaccination, and post-transplant surveillance and prophylaxis, the impact of infections may be reduced.

A digital image colorimetry system based on smart devices for immediate and simultaneous determination of enzyme-linked immunosorbent assays.

Standard enzyme-linked immunosorbent assays based on microplates are frequently utilized for various molecular sensing, disease screening, and nanomedicine applications. Comparing this multi-well plate batched analysis to non-batched or non-standard testing, the diagnosis expenses per patient are drastically reduced. However, the requirement for rather big and pricey readout instruments prevents their application in environments with limited resources, especially in the field. In this work, a handheld cellphone-based colorimetric microplate reader for quick, credible, and novel analysis of digital images of human cancer cell lines at a reasonable price was developed. Using our in-house-developed app, images of the plates are captured and sent to our servers, where they are processed using a machine learning algorithm to produce diagnostic results. Using FDA-approved human epididymis protein of ovary IgG (HE4), prostate cancer cell line (PC3), and bladder cancer cell line (5637) ELISA tests, we successfully examined this mobile platform. The accuracies for the HE4, PC3, and 5637 tests were 93%, 97.5%, and 97.2%, respectively. By contrasting the findings with the measurements made using optical absorption EPOCH microplate readers and optical absorption Tecan microplate readers, this approach was found to be accurate and effective. As a result, digital image colorimetry on smart devices offered a practical, user-friendly, affordable, precise, and effective method for quickly identifying human cancer cell lines. Thus, healthcare providers might use this portable device to carry out high-throughput illness screening, epidemiological investigations or monitor vaccination campaigns.

The effect of Ganoderma lucidum polysaccharide extract on sensitizing prostate cancer cells to flutamide and docetaxel: an in vitro study.

Ganoderma lucidum polysaccharide is the most widely used complementary therapy in cancer. The present study aims to investigate the possible interaction between Ganoderma lucidum polysaccharide and Docetaxel (a chemotherapy drug) and the first-line medication for prostate cancer treatment (Flutamide) and sensitizing the cells to these treatments. The cytotoxic effects of Ganoderma lucidum polysaccharide in combination with Docetaxel and Flutamide on prostate cancer cells were investigated by the MTT test, Hoechst staining, and flow cytometry. In addition, the expression of genes related to apoptosis, angiogenesis, Epithelial-Mesenchymal Transition pathway (EMT), and prostate cancer biomarkers by Real-Time PCR was investigated. The results demonstrated that IC50 values for Ganoderma lucidum polysaccharide (30 µM and 20 µM), Docetaxel (10 µM and 5 µM), and Flutamide (20 µM and 12 µM) with MTT were confirmed by flow cytometry in a dose and time-dependent manner. Regarding the high efficacy of Ganoderma lucidum polysaccharide in combination with Flutamide and Docetaxel, 10 µM and 5 µM Flutamide were used instead of 20 µM and 12 µM and 5 µM and 2 µM Docetaxel was used instead of 10 µM and 5 µM in PC3 and LNCap, respectively. Moreover, for the first time, it was shown that Ganoderma lucidum polysaccharide alone and in combination with Docetaxel and Flutamide significantly augmented apoptosis, reduced cell migration and colonization, and downregulated expression of KLK2 and EMT pathway genes in both PC3 and LNCap cell line (P < 0.01). Ganoderma lucidum polysaccharide synergistically increased the effect of Docetaxel and Flutamide and increased the sensitivity of the prostate cancer cell lines to these drugs. Therefore, it may provide a new therapeutic strategy against prostate cancer.

The impact of conventional smoking versus electronic cigarette on the expression of VEGF, PEMPA1, and PTEN in rat prostate.

Background: The use of electronic cigarettes (e-cigarettes), the alternative to conventional smoking, is increasing considerably worldwide; however, their safety is a matter of debate. Several studies have demonstrated their toxic effects, but no study assessed their effects on the prostate. Objective: The current study aimed at evaluating e-cigarettes and conventional smoking prostate toxicity and effects on the expression of vascular endothelial growth factor A (VEGFA), phosphatase and tensin (PTEN), and prostate transmembrane protein androgen induced 1 (PMEPA1). Method: 30 young Wistar rats were categorized into three groups (n = 10) as follows: the control group, the conventional smoking group, and the e-cigarette group. The case groups were exposed to cigarettes or e-cigarettes for 40 minutes, 3 times a day for four months. Serum parameters, prostate pathology, and gene expression were measured at the end of the intervention. Data were analyzed by Graph Pad prism 9. Results: Histopathological findings presented that both types of cigarette-induced hyperemia and induced inflammatory cell infiltration and hypertrophy of smooth muscle of the vascular wall in the e-cigarette group. Expression of PMEPA1, and VEGFA genes significantly increased in conventional (2.67-fold; P = 0.0108, 1.80-fold; P = 0.0461 respectively) and e-cigarettes (1.98-fold; P = 0.0127, 1.34-fold; P = 0.938, respectively) groups compared to the control group. Expression of the PTEN gene non-significantly decreased in the case of groups compared to the control group. Conclusion: We found no significant differences between the two groups in terms of PTEN and PMEPA1 expression, whereas VEGFA was significantly more expressed in a conventional smoking group compared to the e-cigarette group. Therefore, it seems that e-cigarettes could not be taken into account as a better option than conventional smoking, and quitting smoking still is the optimal option.

Quercetin can be a more reliable treatment for metastatic prostate cancer than the localized disease: An in vitro study.

Quercetin is a plant flavonoid that has been recognized to have anti-inflammatory, antioxidant and anti-proliferative activities. This study aims to evaluate the inhibitory effects of quercetin against prostate malignancy in vitro and the underlying resistance mechanism. IC50 values of quercetin were determined by MTT assay. Annexin-V/PI staining was used to measure the rate of apoptosis. DNA cell cycle was analysed by PI staining method. Real-time PCR was performed to assess mRNA levels of OPN isoforms, VEGF isoforms, P53 and KLK2. Migration potential, proliferative capability and nucleus morphology of cells were evaluated by the scratch-wound assay, colony-forming assay and Hoechst staining, respectively. Quercetin significantly increased the apoptosis rate of PC-3 and LNCaP cell lines, arrested the cell cycle at the sub-G1/G1 phase, and reduced the migration potential and colony-forming capability. Moreover, upregulation of apoptosis-related genes and downregulation of genes involved in proliferation and angiogenesis was also observed. Although our results elucidated that quercetin has antitumor effects on PC-3 and LNCaP, for the first time, we showed that quercetin treatment causes alterations in the expression of OPN and VEGF isoforms, which are cancer-promoting modulators through various processes such as angiogenesis and drug-resistance. Prostate malignant cells can dodge the anti-carcinogenic properties of quercetin via modulation of OPN and VEGF isoforms in vitro. Therefore, quercetin acts as a double-edged sword in prostate cancer treatment.

The effect of mesenchymal stem cells-derived exosomes on the prostate, bladder, and renal cancer cell lines.

We aimed to explain the role of mesenchymal stem cells (MSC-exosomes) on gene expressions of epithelial to mesenchymal transition (EMT), angiogenesis, and apoptosis. Four different cell lines were employed, including ACHN, 5637, LNCaP, and PC3, as well-known representatives for renal, bladder, hormone-sensitive, and hormone-refractory prostate cancers, respectively. Cell lines were exposed to diverse concentrations of mesenchymal stem cells-derived exosomes to find IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining. Micro Culture Tetrazolium Test assessed proliferative inhibitory effect; and prostate biomarker (KLK2), EMT (E-cadherin and Snail), angiogenesis genes (VEGF-A/VEGF-C), apoptosis genes (BAX/BCL2, P53) and Osteopontin variants (OPNa/b, and c) mRNA levels were studied by realtime PCR method. All 5637, LNCaP, and PC3 following treatment with exosomes illustrated specific responses with changes in expression of different genes. The increased TP53 and decreased BCL2 expressions were seen in 5637, LNCaP, and PC3. In PC3, OPNb and OPNc have raised more than P53; in LNCap, the increase was in VEGF-c. In 5637 cells, more than TP53 and BCL2 changes, two other genes, VEGFa and B.A.X., have decreased, suggesting exosomes' anti-apoptotic and anti-angiogenic effects. The kidney tumor cell line saw no significant gene expression change in ten targeted genes. MSC-exosomes therapy has augmented some interesting antitumor effects on prostate, bladder, and kidney cancer cell lines. This effect which originates from exosomes' potency to persuade apoptosis and prevent the proliferation of cancer cells simultaneously, was more substantial in bladder cancer, moderate in prostate cancer, and mild in renal cancer.

Diagnostic Accuracy of Predictive Models in Prostate Cancer: A Systematic Review and Meta-Analysis.

Aim: Accurate diagnosis of prostate cancer (PCa) has a fundamental role in clinical and patient care. Recent advances in diagnostic testing and marker lead to standardized interpretation and increased prescription by clinicians to improve the detection of clinically significant PCa and select patients who strictly require targeted biopsies. Methods: In this study, we present a systematic review of the overall diagnostic accuracy of each testing panel regarding the panel details. In this meta-analysis, using a structured search, Web of Science and PubMed databases were searched up to 23 September 2019 with no restrictions and filters. The study's outcome was the AUC and 95% confidence interval of prediction models. This index was reported as an overall and based on the WHO region and models with/without MRI. Results: The thirteen final articles included 25,691 people. The overall AUC and 95% CI in thirteen studies were 0.78 and 95% CI: 0.73-0.82. The weighted average AUC in the countries of the Americas region was 0.73 (95% CI: 0.70-0.75), and in European countries, it was 0.80 (95% CI: 0.72-0.88). In four studies with MRI, the average weighted AUC was 0.88 (95% CI: 0.86-0.90), while in other articles where MRI was not a parameter in the diagnostic model, the mean AUC was 0.73 (95% CI: 0.70-0.76). Conclusions: The present study's findings showed that MRI significantly improved the detection accuracy of prostate cancer and had the highest discrimination to distinguish candidates for biopsy.

Combined anticancer effects of simvastatin and arsenic trioxide on prostate cancer cell lines via downregulation of the VEGF and OPN isoforms genes.

Arsenic trioxide (ATO) and statins have been demonstrated to have anti-neoplastic properties; however, the data regarding their combination therapy is limited. Thus, we aimed to study the effects of ATO, Simvastatin and their combination in proliferation, apoptosis and pathological angiogenesis in prostate cancer cell lines. The human prostate cell lines were treated with different concentrations of Simvastatin and ATO alone and combined to find effective doses and IC50 values. In addition, the percentage of apoptotic cells was evaluated by annexin/PI staining, and mRNA expression levels of the apoptotic gene, including OPN isoforms and VEGF, were investigated using real-time PCR. Our data displayed that Simvastatin (12 and 8 µM in PC3 and LNCaP cell lines respectively), ATO (8 and 5 µM in PC3 and LNCaP cell lines respectively), and also their combination (12 µM Simvastatin and 8 µM ATO in PC3, 8 µM Simvastatin and 5 µM ATO in LNCaP cell lines respectively) significantly increased the percentage of apoptotic cells. Also, we showed that the combination therapy by Simvastatin and ATO increased cell apoptosis and inhibited cell proliferation, providing anti-proliferative and anti-angiogenic properties, possibly via downregulation of the expression of VEGF and OPN genes. These results provide new perceptions regarding the anticancer roles of ATO and statins' combination therapy in prostate cancer.

Human prostate cancer cell epithelial-to-mesenchymal transition as a novel target of arsenic trioxide and curcumin therapeutic approach.

BACKGROUND: Arsenic trioxide (As2O3) as an inorganic compound is used to treat various cancers and other diseases. It has been reported that arsenic trioxide induced cellular apoptosis in certain kinds of cancers, including prostate cancers. The present study aimed to elucidate the crucial cooperative role of arsenic trioxide and Curcumin and their ability to protect against prostate cancers by targeting the epithelial-to-mesenchymal transition and expression of apoptosis-related genes. MATERIAL AND METHODS: The human prostate cell lines (LNCaP and PC3) were treated with different concentrations of Curcumin and As2O3 alone and combined to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/P.I. staining, the proliferative inhibitory effect was assessed by Micro Culture Tetrazolium Test (MTT), and mRNA levels of KLK2, E-cadherin, SNAIL, angiogenesis genes (VEGFA and VEGFC), and apoptosis genes (BAX, Bcl2, and P53) expression were investigated by the real-time PCR method. ANOVA and t-test were used to appraise the results. RESULTS: For the first time, we presented that the combination therapy of Curcumin and As2O3 increases prostate cancer cell apoptosis and inhibits proliferation; Our data displayed that Curcumin (15 µM and 10 µM in PC3 and LNCap), As2O3 (8 µM and 5 µM in PC3 and LNCap), and also their combination (15 µM Curcumin and 8 µM As2O3 in PC3, 10 µM Curcumin and 5 µM As2O3 in LNCap cell lines) significantly increased the percentage of apoptotic cells and inhibited cell growth (P < 0.05) compared with each drug alone. Generally, both cell lines treated with the combination of Curcumin and As2O3 displayed decreased angiogenesis genes (VEGFA and VEGFC), apoptosis genes (BAX and Bcl2), and prostate cancer marker (KLK2), the zinc-finger protein (SNAIL); and an increase in expression (P < 0.05) of cell-cell adhesion molecule (E-cadherin) and tumor suppressor gene (P53) genes. CONCLUSIONS: The antitumor effects of combination therapy with As2O3 and Curcumin have been displayed on prostate cancer cell lines (LNCaP and PC3), which probably originates from their potential to induce apoptosis and inhibit the growth of prostate cancer cells simultaneously.

Novel combination therapy of prostate cancer cells with arsenic trioxide and flutamide: An in-vitro study.

OBJECTIVE: The study objective was to assess the therapeutic potential of Arsenic Trioxide (ATO) and Flutamide combination for metastatic prostate cancer (PCa) treatment. MATERIAL AND METHOD: LNCaP and PC3 cell lines were treated with different concentrations of ATO and PCa conventional drug Flutamide alone and/or in combination to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and the proliferative inhibitory effect was assessed by Micro Culture Tetrazolium Test (MTT). Expression of SNAIL, KLK2, E-cadherin, and angiogenesis genes (VEGFA and VEGFC), and apoptosis genes (Bcl2, and P53) were examined by real-time PCR. RESULTS: The combination of Flutamide and ATO significantly increased the percentage of apoptotic cells and inhibited PCa cells proliferation compared with each drug alone in LNCaP and PC3 cell lines. Generally, both cell lines treated with the combination of Flutamide and ATO showed a decrease in expression of KLK2, angiogenesis genes (VEGFA and VEGFC), and apoptosis gene (Bcl2), and an increase in expression of E-cadherin and P53 genes; however, contradictory findings were found regarding SNAIL expression in LNCaP and PC3 cells. CONCLUSION: The combination therapy with ATO and flutamide has augmented the anti-tumor effect on LNCaP and PC3 cells, which probably originates from their potential to induce apoptosis and inhibit the proliferation of PCa cells simultaneously.

Osteopontin b and c Splice isoforms in Leukemias and Solid Tumors: Angiogenesis Alongside Chemoresistance

Osteopontin (OPN) is a glycoprotein involved in regulation of various influences on tumor progression, such as cellular proliferation, apoptosis, angiogenesis, and metastasis. Vascular endothelial growth factor (VEGF) is a secreted molecule supporting angiogenesis in various cancers through activation of the PI3K/AKT/ERK1/2 pathway. OPN and VEGF have a number of isoforms with various activities. In spite of the well-defined association between OPN and VEGF isoform expression and cure rate for solid tumors, there is a scarcity of information as to any association in leukemia. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that OPN and VEGF isoform expression levels may impact on chemoresistance and relapse in leukemia the same as in solid tumors. Hence, the aim of our review was to explain relationships between OPN and VEGF isoforms and angiogenesis and related pathways in chemoresistance of leukemia and solid tumors. Our findings demonstrated that OPNb and OPNc alongside with VEGF isoforms and other gene pathways are involved in angiogenesis and also might promote chemoresistance and even recurrence in leukemia and solid tumors. To sum up, targeting OPN isoforms, particularly b and c, might be a novel therapeutic strategy for the treatment of leukemia as well as solid tumors.

OPN b and c Isoforms Doubtless Veto Anti-angiogenesis Effects of Curcumin in Combination with Conventional AML Regiment

Osteopontin (OPN) is an extracellular structural protein that is secreted by osteoblasts and hematopoietic cells. It suppresses the proliferation of hematopoietic stem and also plays an important role in promoting survival and drug resistance in leukemic stem cells (LSCs). Since the role of OPN isoforms in AML angiogenesis are remaining controversial, in the present study, we aimed to evaluate whether curcumin (CUR), as a known natural component with anti-angiogenesis effects, in a combination of AML conventional regiment has the potency to preclude induced anti-angiogenesis effects of OPN isoforms or not? Leukemia cells were treated with different concentration of CUR and AML conventional drugs alone and/or in combination with together to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and mRNA levels of OPN isoforms and AKT/ VEGF-A and VEGF-C/ STAT3/ ß-catenin/ CXCR4/ IL-6/ KDR gene expression were investigated by Real Time-PCR method. Moreover, to confirm OPN gene expression data, we investigated the effect of simvastatin and OPN siRNA as an OPN inhibitor on the cell proliferation and induction of apoptosis in the indicated cell lines. Our data display that Ara-c (2µM and 1µM in KG-1 and U937 cell lines respectively), CUR (40µM in both cell lines), and also their combination significantly increased the percentage of apoptotic cells. Moreover, the mRNA level of OPN isoforms were down regulated in the KG-1and U937 cell lines treated with Ara-c while, upregulated in KG-1and U937 cell lines treated with CUR and its combination. Our results suggest that despite anti-angiogenesis effects of CUR, AML cells probably evade from anti-angiogenesis effects of CUR via induction of OPN b and c isoform and related molecular pathways.

Osteopontin b and c isoforms: Molecular Candidates Associated with Leukemic Stem Cell Chemoresistance in Acute Myeloid Leukemia

Despite impressive advances in therapeutic approaches, long-term survival with acute myeloid leukemia (AML) is low as a result of treatment resistance and frequent relapse. Among multitude oncogenic proteins involved in acquisition of a chemo-resistanr phenotype, osteopontin (OPN) recently has attracted marked attention. In spite of the well-defined association between OPN expression and cure rate with solid tumors, there is a scarcity of information on any role of this protein in AML cases. Based on the critical role of OPN in cell survival, it seems reasonable to hypothesize that isoform expression levels may impact on regulation of apoptosis in AML cells in response to conventional chemotherapeutic drugs and its relation to relapse. To investigate associations between induction of apoptosis and OPN isoform expression, two distinct AML cell lines (KG-1 as a leukemic stem cell model and U937) were treated with chemotherapy drugs, and cell viability and apoptosis were evaluated by MTT and Annexin/PI assay. After determination of appropriate drug doses, mRNA expression levels of OPN isoforms and OPN-related genes were investigated. Our results demonstrated for the first time that acquired up-regulation of OPN-b and c isoforms might prevent conventional chemotherapy regimen-induced apoptosis in AML cells. Moreover, upregulation of OPN-b and c in AML cells appears concurrent with upregulation of AKT/VEGF/CXCR4/STAT3/ IL-6 gene expression. To sum up, this study suggests that OPN-b and c isoforms could be considered as unique beneficial molecular biomarkers associated with leukemic stem cell chemoresistance. Hence, they have potential as molecular candidates for detection of minimal residual disease (MRD) and determination of remission in AML patients. Further evaluation with quantative real time PCR on patient samples for confirmation appears warranted.