Antiproliferative activity of new pentacyclic triterpene and a saponin from Gladiolus segetum Ker-Gawl corms supported by molecular docking study

A new triterpenoidal saponin identified as 3-O-[β-d-glucopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 4)-β-d-xylopyranosyl]-2β,3β,16α-trihydroxyolean-12-en-23,28-dioic acid-28-O-α-l-rhamnopyranosyl-(1 → 4)-α-l-rhamnopyranosyl-(1 → 2)-β-d-glucopyranosyl-(1 → 2)-α-l-arabinopyranoside 1 together with a new oleanane triterpene identified as 2β,3β,13α,22α-tetrahydroxy olean-23,28-dioic acid 2 and 6 known compounds (3–8) have been isolated from Gladiolus segetum Ker-Gawl corms. The structural elucidation of the isolated compounds was confirmed using different chemical and spectroscopic methods, including 1D and 2D NMR experiments as well as HR-ESI-MS. Moreover, the in vitro cytotoxic activity of the fractions and that of the isolated compounds 1–8 were investigated against five human cancer cell lines (PC-3, A-549, HePG-2, MCF-7 and HCT-116) using doxorubicin as a reference drug. The results showed that the saponin fraction exhibited potent in vitro cytotoxic activity against the five human cancer cell lines, whereas the maximum activity was exhibited against the PC-3 and A-549 cell lines with the IC₅₀ values of 1.13 and 1.98 μg mL⁻¹, respectively. In addition, compound 1 exhibited potent activity against A-549 and PC-3 with the IC₅₀ values of 2.41 μg mL⁻¹ and 3.45 μg mL⁻¹, respectively. Interestingly, compound 2 showed the maximum activity against PC-3 with an IC₅₀ of 2.01 μg mL⁻¹. These biological results were in harmony with that of the molecular modeling study, which showed that the cytotoxic activity of compound 2 might occur through the inhibition of the HER-2 enzyme.

A new triterpenoidal saponin 1, a new oleanane triterpene 2, and 6 known compounds (3–8) have been isolated from Gladiolus segetum Ker-Gawl corms.     

Safety of not withholding clopidogrel therapy during the immediate several days pre- and post-trans-urethral resection of prostate (TURP): a retrospective cohort study

Background and aim

Benign prostatic hypertrophy or hyperplasia (BPH) is a frequent urological complain particularly in old-aged individuals. Those patients usually have other risk factors (such as ischemic cardiovascular diseases) for which they might be treated with anti-thrombotic agents chronically. These medicines may induce blood thinning and raise the incidence of hemorrhage. Thus, if those patients needed operative treatment for BPH, they may be at high risk of hemorrhage or its related adverse effects with the usage of anti-thrombotic drugs during the peri-operative time. On the other hand, dis-continuation of these agents can lead to ischemic events in susceptible individuals.

Therefore, this research aims to assess the safety of the continuation of using anti-thrombotic agents throughout the peri-operative duration in patients with prostate surgery in form of Transurethral Resection of Prostate (TURP) only for Benign Prostatic Hypertrophy (BPH).

Methods

Patients’ notes were reviewed retrospectively. The entire participants were categorized into two categories. First category was on clopidogrel therapy (CTC) for prolong time and the usage of these agents was carried on throughout the peri-operative period. The second category was not on clopidogrel therapy at all (NCTC). Both of these categories had Transurethral Resection of Prostate (TURP) for Benign Prostatic Hypertrophy (BPH). A comparison had been conducted between the two categories with regards to: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (PRBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge. Pearson Chi-square test, Independent sample t test and test for numeric variables were used as appropriate.

Results

The study identified 329 patients. One hundred and sixty five participants in the CTC (clopidogrel therapy category) and 164 in the NCTC (non-clopidogrel therapy category). It had been revealed that there was no statistically significant difference between the CTC and NCTC regarding: (i) the amount of blood lost intra-operatively (ii) the duration of operation (iii) hematocrit concentration per-operatively (iv) transfused packed red blood cells (packed RBC) if needed (v) clearance of hematuria postoperatively (vi) secondary hemorrhage and clot retention after discharge (P?>?0.65).

Conclusion

The continuation of usage of anti-thrombotic therapy (clopidogrel) during peri-operative period in patients with TURP for BPH is a safe practice. It is not associated with high probability of hemorrhage or PRBC transfusion or other adverse effects.

     

The Clinical and Prognostic Implications of Pluripotent Stem Cell Markers Expression and Their Correlation with the WNT signal pathway in Hepatocellular Carcinoma

Objectives: This study aimed to investigate the expression of SOX2, SOX9, p53, and β-catenin in hepatocellular carcinoma (HCC) and their correlation with clinicopathological parameters of prognostic importance. Materials and Methods: Seventy-five patients were enrolled in this study. All patients had full clinical and follow-up data and available paraffin blocks. Immunohistochemical analysis was performed and correlated with clinicopathological factors and patient survival. Results: We detected the positive expression of SOX2, SOX9, p53, and β-catenin in 76%, 50.7%, 50.7%, and 77.9% of HCC specimens respectively. All studied markers showed a significant increase in the expression in tumor tissue specimens compared to non-tumor tissue. Both SOX2 and SOX9 expressions were significantly associated with adverse prognostic factors in HCC. Significant positive correlations were found between SOX2 and SOX9 and both p53 and β-catenin expression (r= 0.528, 0.485 and; r = 0.253, 0.327, respectively; p < 0.0001 for both of them). Regarding survival, we found that HCC patients with positive SOX2 and SOX9 expressions had significantly shorter overall survival (p=0.0001, each). Additionally, larger tumor size, tumor grade, high stage, tumor multiplicity, presence of cirrhosis, tumor necrosis, high p53 expression, and positive β-catenin expression were independent predictors of worse survival. A multivariate Cox analysis revealed that tumor grade, stage, p53, and SOX2 expression were independent predictors of unfavorable prognosis in overall survival (p=0.0001, p=0.0001,p=0.033; and p=0.003, respectively). Conclusions: Our findings might provide an insight into SOX2 and SOX9’s role in HCC and suggest that SOX2 might be targeted for HCC therapy.     

Serum and blister fluid levels of cytokines and chemokines in pemphigus and bullous pemphigoid

Bullous pemphigoid and pemphigus constitute two major autoimmune blistering diseases (AIBD) with complicated disease pathomechanisms involving a multitude of cytokines and immunological pathways. The purpose of our literature review of the cytokines and chemokines involved in these AIBDs was to allow for a meta-analysis of studies detailing differential cytokine and chemokine changes in these conditions. Elucidation of inflammatory pathways could lead to more targeted therapies, several of which specific monoclonal antibodies already exist and are used safely for other autoimmune diseases. A systematic review of the Pubmed/Medline database was performed for articles characterizing cytokines/chemokines involved in BP and pemphigus. Further, a meta-analysis was carried out using standardized methods, including assessment for heterogeneity. The results of our analysis demonstrated numerous inflammatory alterations in these AIBDs. Significant alterations included serum levels of IL-5, IL-6, IL-8, IL-17, CCL-17, and CCL-26 in patients with BP, and increased blister fluids levels of IL-5, IL-6, IL-8, CCL11, and TNF-α. Blister fluid levels of IL-1α are decreased in BP. In pemphigus, we identified significantly increased serum levels of IL-10, IL-17, and CCL17. We have additionally summarized all studies excluded from meta-analysis to provide a comprehensive summary of cytokine/chemokine alterations in these two conditions.     

Quantitative Monitoring of Extracellular Matrix Production in Bone Implants by <Superscript>13</Superscript>C and <Superscript>31</Superscript>P Solid-State Nuclear Magnetic Resonance Spectroscopy

We used ³¹P and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopy to detect and analyze the major organic and inorganic components (collagen type I and bioapatite) in natural rabbit bone and β-tricalcium phosphate implants loaded with osteogenically differentiated mesenchymal stem cells. High-resolution solid-state NMR spectra were obtained using the magic-angle spinning (MAS) technique. The ³¹P NMR spectra of bone specimens showed a single line characteristic of bone calcium phosphate. ¹³C cross-polarization (CP) MAS NMR spectra of bone exhibited the characteristic signatures of collagen type I with good resolution for all major amino acids in collagen. Quantitative measurements of ¹³C-¹H dipolar couplings indicated that the collagen segments are very rigid, undergoing only small amplitude fluctuations with correlation times in the nanosecond range. In contrast, directly polarized ¹³C MAS NMR spectra of rabbit bone were dominated by signals of highly mobile triglycerides. These quantitative investigations of natural bone may provide the basis for a quality control of various osteoinductive bone substitutes. We studied the formation of extracellular bone matrix in artificial mesenchymal stem cell-loaded β-tricalcium phosphate matrices that were implanted into the femoral condyle of rabbits. The NMR spectra of these bone grafts were acquired 3 months after implantation. In the ³¹P NMR spectra, β-tricalcium phosphate and bone calcium phosphate could be distinguished quantitatively, allowing recording of the formation of the natural bone matrix. Further, ¹³C CPMAS allowed detection of collagen type I that had been produced in the implants. Comparison with the spectroscopic data from natural bone allowed assessment of the quality of the bone substitute material. J. S. and M. P. contributed equally to this study     

Ketamine hydrochloride as sole anesthetic for open liver biopsy

We evaluated the use of ketamine as sole anesthetic agent for open liver biopsy, with particular reference to its effect on liver function and hepatotoxicity and its effect on cardiovascular stability and respiration. From 386 patients who underwent liver biopsy at Jordan University Hospital, 12 had open liver biopsy because of contra-indications for closed needle biopsy. The surgical procedure consisted of a small right paramedian incision allowing inspection of the liver surface and a wedge and needle biopsy. Ketamine HCl was used in a dose of 2 mg/kg I.V. with supplemental doses as necessary. No significant fluctuations in cardio-respiratory vital signs were observed. Muscle rigidity and respiratory tagging movements necessitated addition of a muscle relaxant and artificial ventilation in three patients. Six patients reported dreams, two of which were described as nightmares. There was no liver function decompensation, or significant bilirubin or transaminase elevations in the week following the biopsy. Ketamine is a safe anesthetic to use for open liver biopsy in patients with underlying liver disease, although poor muscle relaxation and nightmares may be significant side effects.     

A new study of acupuncture in IVF: pointing in the right direction

New emerging evidence from clinical trials demonstrates that acupuncture performed at the time of embryo transfer does not improve the pregnancy or live birth outcome after treatment. This evidence raises questions regarding the futility of conducting further research in this area and the quality of evidence needed before any specific intervention is incorporated into routine clinical practice, particularly when a scientific rationale is lacking.