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Survivin is an inhibitor of apoptosis as well as a promoter of cell proliferation. Fibulin-3 is a matrix glycoprotein that displays potential for tumor suppression or propagation. The present study aimed to validate the expression levels of survivin and fibulin-3 in benign and malignant respiratory diseases. This case–control study included 219 patients categorized into five groups. Group A included 63 patients with lung cancer, group B included 63 patients with various benign lung diseases, group D included 45 patients with malignant pleural mesothelioma (MPM), and group E included 48 patients with various benign pleural diseases. Group C included 60 healthy individuals (control group). Serum survivin and fibulin-3 levels were measured by ELISA, whereas their nuclear expressions in the lung and pleura were assessed via Western blot analysis. The results showed significantly higher survivin serum levels and significantly lower fibulin-3 levels in group A compared with in group B and controls (P<0.001). There were significantly higher serum levels of survivin and fibulin-3 in group D compared with in group E and controls (P<0.001), consistent with observed nuclear survivin and fibulin-3 expression levels. Fibulin-3 was determined to have higher value than survivin in discriminating lung cancer from MPM (P<0.05). Survivin and fibulin-3 could be useful diagnostic markers for lung and pleural cancers, and fibulin-3 expression was particularly useful in differentiating lung cancer from MPM.

Over the past 30 years, no consistent survival benefits have been recorded for anticancer agents of advanced hepatocellular carcinoma (HCC), except for the multikinase inhibitor sorafenib (Nexavar ), which clinically achieves only ~3 months overall survival benefit. This modest benefit is attributed to limited aqueous solubility, slow dissolution rate and, consequently, limited absorption from the gastrointestinal tract. Thus, novel formulation modalities are in demand to improve the bioavailability of the drug to attack HCC in a more efficient manner. In the current study, we aimed to design a novel sorafenib-loaded carbon nanotubes (CNTs) formula that is able to improve the therapeutic efficacy of carried cargo against HCC and subsequently investigate the antitumour activity of this formula. Sorafenib was loaded on functionalized CNTs through physical adsorption, and an alginate-based method was subsequently applied to microcapsulate the drug-loaded CNTs (CNTs-SFN). The therapeutic efficacy of the new formula was estimated and compared to that of conventional sorafenib, both in vitro (against HepG2 cells) and in vivo (in a DENA-induced HCC rat model). The in vitro MTT anti-proliferative assay revealed that the drug-loaded CNTs formula was at least two-fold more cytotoxic towards HepG2 cells than was sorafenib itself. Moreover, the in vivo animal experiments proved that our innovative formula was superior to conventional sorafenib at all assessed end points. Circulating AFP-L3% was significantly decreased in the CNTs-SFN-MCs-treated group (14.0%) in comparison to that of the DENA (40.3%) and sorafenib (38.8%) groups. This superiority was further confirmed by Western blot analysis and immunofluorescence assessment of some HCC-relevant biomarkers. Our results firmly suggest the distinctive cancer-suppressive nature of CNTs-SFN-MCs, both against HepG2 cells in vitro and in a DENA-induced HCC rat model in vivo, with a preferential superiority over conventional sorafenib.

Polycyclic aromatic hydrocarbons (PAHs)/aryl hydrocarbon receptor (AhR) regulate the expression of target genes, including drug transporter genes which harbor xenobiotic response element (XRE) in their promoter regions. Thus, PAHs/AhR could alter the toxicokinetic profile of many nephrotoxic drugs, including aminoglycosides. In the current study, we investigated the expression and localization of AhR and megalin in rat kidney. Furthermore, we investigated whether AhR and its ligands could modulate the expression of megalin and consequently the gentamicin-induced nephrotoxicity (GN) in rats. Both megalin and AhR receptors are expressed in the proximal tubules of the rat kidney. Treatment with AhR agonist benzo( a )pyrene aggravated GN as indicated by a significant increase in serum creatinine, BUN, KIM1, NAGL, CD-86, and urinary albumin/creatinine ratio. On the other hand, treatment with AhR antagonist resveratrol ameliorated GN as manifested by a pronounced decrease in the aforementioned parameters. The effects of AhR ligands on GN were associated with altered expression of megalin receptor.

Introduction: Traumatic spinal cord injury (TSCI) is a life-threatening neurological disorder and there is a lack of biomarker research, particularly human studies that could help to categorize the severity and predict the outcome. We aimed to assess the role of serum Ubiquitin C-terminal hydrolase L1 (UCH-L1) and Neuroglobin (NGB) in predicting severity and outcome of TSCI. Methods: This prospective study included 63 participants categorized into 33 patients with various types of TSCI and 30 unrelated healthy volunteers. Neurosurgical [American spinal injury association (ASIA) impairment score (AIS)] and radiological [using spine computed tomography (CT) and magnetic resonance imaging (MRI)] assessments were performed on the included patients to determine the severity and the level of injury with neurological follow-up of patients within 6 months post-injury. Serum UCH-L1 and NGB were measured for all participants using commercially available ELISA assay kits. Results: Of the included patients, 20 (60.60%) had partial SCI and the remaining 13 patients (39.39%) had complete SCI. On follow-up, 19 patients (57.57%) showed improved AIS, while 14 cases (42.42%) did not show any improvement in their AIS scores. There was significantly higher median serum UCHL1 value among cases compared to controls (1723 pg/mL and 657 pg/mL, respectively), p < 0.05. There was an insignificant rise of serum NGB levels among cases in comparison with the controls (15.2pg/mL and 7.52pg/mL, respectively, p > 0.05). Significantly lower initial median serum UCHL1 levels (pg/mL) were observed in patients with improved AIS during the neurological follow-up compared with those who did not show any improvement in their AIS score (1723, and 4700 respectively, p < 0.05), with lack of significant difference in the initial median serum NGB levels, p > 0.05. Conclusion: Initial serum UCHL1 assay could be a helpful marker in reflecting the degree of TSCI and predicting its outcome, though NGB needs further assessment. Keywords: traumatic spinal cord injury, Ubiquitin C-terminal hydrolase L1, neuroglobin, diagnostic and prognostic markers

Introduction: Verruca vulgaris is a benign hyperkeratotic proliferation of the epidermis. Few studies look at the differences in serum and tissue macrophage migration inhibitory factor (MIF) levels in verruca vulgaris, as well as its gene polymorphisms that have yet to be explored. The current study provided in-depth evaluation of MIF in serum and tissues of patients with verruca vulgaris, and establishes for the first time the possible association of MIF gene polymorphisms with common warts. Methods: This case-control study included 50 patients who were diagnosed clinically as common warts in comparison with 50 age and sex-matched controls. Clinical examination was done on all included cases. Serum MIF was measured using enzyme- linked immunosorbent assay (ELISA), while its tissue expression was analyzed using Western blotting and immunohistochemical techniques for the included participants. Analysis of MIF-173 G>C single nucleotide polymorphism was performed by polymerase chain reaction (PCR) using restriction fragment length polymorphism (RFLP) technique. Results: The overall results revealed significantly lower MIF tissue expression in lesional and perilesional skin biopsies from cases compared to the controls using Western blot and immunohistochemical analysis. Yet, the difference in the serum MIF levels between cases and controls was not significant (p > 0.05). GC genotype of the studied MIF rs755622 G>C SNP could be considered as a protective genetic factor against the occurrence of verruca vulgaris among Egyptians with OR (95% CI) equal 0.444 (0.199-0.989). Conclusion: MIF and its genetic variants are thought to play a pathogenic role in verruca vulgaris development and recurrence. Keywords: macrophage migration inhibitory factor, MIF rs755622 G>C SNP, common warts, RFLP-PCR, western blot, immimohistochemistry

A new group of thiazolidine-2,4-dione derivatives of ciprofloxacin having butyryl linker 3a-l was synthesized via an alkylation of thiazolidine-2,4-diones with butyryl ciprofloxacin with yield range 48–77% andfully characterized by various spectroscopic and analytical tools. Anti-cancer screening outcomes indicated that 3a and 3i possess antiproliferative activities against human melanoma LOX IMVI cancer cell line with IC 50 values of 26.7 ± 1.50 and 25.4 ± 1.43 µM, respectively, using doxorubicin and cisplatin as positive controls with an IC 50 of 7.03 ± 0.40 and 5.07 ± 0.29 µM, respectively. Additionally, compound 3j showed promising anticancer activity against human renal cancer A498 cell line with IC 50 value of 33.9 ± 1.91 µM while doxorubicin and cisplatin showed IC 50 values of 3.59 ± 0.20 and 7.92 ± 0.45, respectively. On the other hand, compound 3i did not show considerable anti-bacterial activity against S. aureus , E. coli and P. aeruginosa , a nd only moderate activity against K. pneumoniae with only a tenth of the activity of ciprofloxacin, confirming the cytotoxicity observed. Mechanistically, compound 3i inhibited both topoisomerase I and II with IC 50 of 4.77 ± 0.26 and 15 ± 0.81 µM. Furthermore, it induced cell cycle arrest at S phase in melanoma LOX IMVI cells. Moreover, 3i provoked substantial levels of early, late apoptosis and necrosis in melanoma LOX IMVI cell line comparable to that induced by doxorubicin. Furthermore, compound 3i increased the expression level of active caspase-3 by 49 folds higher in LOX IMVI cell, increased protein expression level of Bax more than the control by 3 folds and inhibited PARP-1by 33% in LOX IMVI. All results were supported by theoretical docking studies on both tested enzymes confirming potential cytotoxicity for the synthesized hybrids.

Purpose The purpose of this study was to compare the modulation effects of Microcurrent Therapy (MT) and Low-Level Laser Therapy (LLLT) on Matrix Metalloproteinases (MMPs) and tissue inhibitors of Metalloproteinases (TIMPs) expressions during healing of surgical wounds using appendectomy wound as a model. Methods Ninety patients who recently underwent appendectomy were randomly divided into 3 main groups of equal numbers. All cases in the three groups received ordinary medical therapy. Moreover, group A (MT group) received Microcurrent Therapy for 20 min. In addition to a designed physical therapy treatment protocol for 20 min. Group B (LLLT group) received Low-Level Laser Therapy for 20 min., plus the same designed physical therapy treatment protocol for 20 min. Group C (placebo group) received placebo shame LLLT for 20 min. plus the same designed physical therapy treatment protocol for 20 min. Enzyme-linked immunosorbent assay (ELISA) and Western Blot Technique (WBT) were used to determine expression levels of MMP-8, MMP-9, and TIMP-1 at the beginning of treatment and after the end of twelve successive sessions. Results Following therapies, results showed a statistically significant decrease in the MMP-8 and MMP-9 expressions with significantly increased expression levels of TIMP-1 in each group separately ( P  < 0.05). These changes in the expression levels towards proper healing of surgical wounds were more obvious in MT and LLLT groups compared to the placebo group, with significantly better effect in the LLLT group compared to the MT group . Conclusion Microcurrent therapy and low-level laser therapy have a notable impact in improving wound healing process as they can significantly affect the expression levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases towards good prognosis of healing process and decreasing possible wound healing complication, with superior effect of low-level laser therapy.

Tolmetin sodium (TLM) is a non-steroidal anti-inflammatory drug (NSAIDs). TLM is used to treat inflammation, skeletal muscle injuries, and discomfort associated with bone disorders. Because of the delayed absorption from the gastro intestinal tract (GIT), the currently available TLM dosage forms have a rather protracted start to the effect, according to pharmacokinetic studies. The aim of this study was to create a combination for TLM fast dissolving tablets (TLM-FDT) that would boost the drug’s bioavailability by increasing pre-gastric absorption. The TLM-FDTs were developed using a Box-Behnken experimental design with varied doses of crospovidone (CP), croscarmellose sodium (CCS) as super-disintegrants, and camphor as a sublimating agent. In addition, the current study used response surface approach to explore the influence of various formulation and process factors on tablet qualities in order to verify an optimized TLM-FDTs formulation. The optimized TLM-FDTs formula was subsequently evaluated for its in vivo anti-inflammatory activity. TLM-FDTs have good friability, disintegration time, drug release, and wetting time, as well as fast disintegration and dissolution behavior. Significant increase in drug bioavailability and reliable anti-inflammatory efficacy were also observed, as evidenced by considerable reductions in paw thickness in rats following carrageenan-induced rat paw edema. For optimizing and analyzing the effect of super-disintegrants and sublimating agents in the TLM-FDTs formula, the three-factor, three-level full factorial design is a suitable tool. TLM-FDTs are a possible drug delivery system for enhancing TLM bioavailability and could be used to treat rheumatoid arthritis.

Osteoarthritis (OA) etiology and pathogenesis not yet fully understood. We studied the role of vitamin D receptor single-nucleotide polymorphisms (VDR-SNPs), vitamin D3, serum and synovial macrophage migration inhibitory factor (MIF), and tumor necrosis factor-α (TNF-α) in the development and progression of knee OA (KOA). This study included 205 Egyptian subjects (105 patients with KOA and 100 unrelated, healthy matched subjects selected as controls). The patient group was divided into three groups according to KOA severity (mild, moderate, and severe), with 35 patients in each group. The polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) technique was used for the ApaI and TaqI SNPs. Vitamin D, serum and synovial TNF-α, and MIF assays were performed using ELISA kits. There were significantly lower serum levels of 25-hydroxycholecalciferol with significant increasing TNF-α and MIF levels in relation to disease severity among the cases (all: p˂0.05).Wild homozygous and heterozygous mutant genotypes (GG+GT) and G allele of ApaI demonstrated risk for KOA development, with odds ratio OR = 6.313 (95% confidence interval (CI) 2.074–19.210) and OR = 1.532 (95%CI 1.013–2.317), respectively. Homozygous mutant CC genotype and C allele of TaqI could be considered a risk factor associated with KOA development, with OR = 2.667 (95%CI 1.270–5.601) and OR = 0.737 (95%CI 0.496–1.095), respectively. VDR-SNPs, vitamin D3, TNF-α, and MIF could play an essential role in the pathogenesis and progression of KOA with mechanistic associations.

Hepatocellular carcinoma (HCC) is a prevalent cancer worldwide. Late-stage detection, ineffective treatments, and tumor recurrence contribute to the low survival rate of the HCC. Conventional chemotherapeutic drugs, like doxorubicin (DOX), are associated with severe side effects, limited effectiveness, and tumor resistance. To improve therapeutic outcomes and minimize these drawbacks, combination therapy with natural drugs is being researched. Herein, we assessed the antitumor efficacy of Ceiba pentandra ethyl acetate extract alone and in combination with DOX against diethylnitrosamine (DENA)-induced HCC in rats. Our in vivo study significantly revealed improvement in the liver-function biochemical markers (ALT, AST, GGT, and ALP), the tumor marker (AFP-L3), and the histopathological features of the treated groups. A UHPLC-Q-TOF-MS/MS analysis of the Ceiba pentandra ethyl acetate extract enabled the identification of fifty phytomolecules. Among these are the dietary flavonoids known to have anticancer, anti-inflammatory, and antioxidant qualities: protocatechuic acid, procyanidin B2, epicatechin, rutin, quercitrin, quercetin, kaempferol, naringenin, and apigenin. Our findings highlight C. pentandra as an affordable source of phytochemicals with possible chemosensitizing effects, which could be an intriguing candidate for the development of liver cancer therapy, particularly in combination with chemotherapeutic drugs.