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Objectives: The objective of this study was to examine the concordance of a grading scale (0–4) of medial femoral osteophytes in knee joint detected by ultrasound (US) compared with the corresponding grades (0-4) of Kellgren-Lawrence (K＆L) scale of conventional radiography and clinical joint examination. Patients and methods: A cross-sectional observational study included 160 patients with knee pain who fulfilled the American College of Rheumatology (ACR) criteria for knee osteoarthritis (KOA) and 20 patients with knee pain who have not fulfilled the ACR criteria for KOA. All patients were subjected to clinical assessment (Western Ontario and McMaster Universities Index of Osteoarthritis and global visual analog scale) and radiological assessment in the form of X-ray grading according to K＆L grading scale and ultrasonographic assessment of medial femoral osteophytes according to a scale that was proposed by the first author and consisted of five grades (0-4), where grade 0 denoted no osteoarthritis and grade 4 denoted the most advanced grade of KOA. Grade 2 was divided into two subgrades A and B with grade 2B considered as a more advanced stage than grade 2A. Results: The proposed US grading scale had high sensitivity and specificity in detecting the different grades of KOA compared with K＆L grading scale (a total sensitivity of 94.6% and a total specificity of 93.3%). Intra- and interreader reliability of US was excellent (kappa .0.93 and .0.85, respectively). Co nclusio ns: US can reliably detect the severity of KOA. Good agreement was found between the proposed US grading scale and K＆L grading scale. The proposed US grading scale is simple and reliable.

End-stage renal disease (ESRD) is associated with chronic kidney disease-mineral and bone disorder (CKD-MBD); including renal osteodystrophy, and biochemical changes reflecting mineral and hormonal abnormalities. CKD-MBD can lead to serious musculoskeletal manifestations with an impact on the functional status of patients. The objective is to find the frequency of the musculoskeletal manifestations in dialysis patients, to determine the impact on the functional ability of patients, and to detect the relation between parathyroid hormone (PTH) level and musculoskeletal manifestations. The sample size included 53 adult patients on hemodialysis (HD), three times weekly, divided into two groups as follows; (Group A) included 15 patients (10 males and 5 females) on HD for a year or <1 year and (Group B) included 38 patients (24 males and 14 females) on HD for >1 year. All patients were subjected to a full history and physical examination plus a comprehensive assessment of patient’s disability was done with a health assessment questionnaire (HAQ)-disability index. The most common neurological manifestations are uremic polyneuropathy (43.4%) and carpal tunnel syndrome. Arthralgia is the most common musculoskeletal manifestation (83%).The most common radiological signs of SHPT is the subperiosteal resorption of the terminal phalanges (67.9%). The most common MSUS abnormalities are Achilles tendinopathy (67.9%). Osteoporosis is detected in 24.5% of patient. There are highly positive significant correlations between HAQ score and age, HD duration, serum PTH, T-score, and X-ray findings. Musculoskeletal system involvement remains a common problem which decreases the physical function of patients with ESRD.

In this study isolates from Thymelaea hirsuta, a wild plant from the Sinai Peninsula of Egypt, were identified and their selective cytotoxicity levels were evaluated. Phytochemical examination of the ethyl acetate (EtOAc) fraction of the methanolic (MeOH) extract of the plant led to the isolation of a new triflavanone compound (1), in addition to the isolation of nine previously reported compounds. These included five dicoumarinyl ethers found in Thymelaea: daphnoretin methyl ether (2), rutamontine (3), neodaphnoretin (4), acetyldaphnoretin (5), and edgeworthin (6); two flavonoids: genkwanin (7) and trans-tiliroside (8); p-hydroxy benzoic acid (9) and β sitosterol glucoside (10). Eight of the isolated compounds were tested for in vitro cytotoxicity against Vero and HepG2 cell lines using a sulforhodamine-B (SRB) assay. Compounds 1, 2 and 5 exhibited remarkable cytotoxic activities against HepG2 cells, with IC50 values of 8.6, 12.3 and 9.4 μM, respectively, yet these compounds exhibited non-toxic activities against the Vero cells. Additionally, compound 1 further exhibited promising cytotoxic activity against both MCF-7 and HCT-116 cells, with IC50 values of 4.26 and 9.6 μM, respectively. Compound 1 significantly stimulated apoptotic breast cancer cell death, resulting in a 14.97-fold increase and arresting 40.57% of the cell population at the Pre-G1 stage of the cell cycle. Finally, its apoptosis-inducing activity was further validated through activation of BAX and caspase-9, and inhibition of BCL2 levels. In silico molecular docking experiments revealed a good binding mode profile of the isolates towards Ras activation/pathway mitogen-activated protein kinase (Ras/MAPK); a common molecular pathway in the development and progression of liver tumors.

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

Thoracolumbar interfascial plane (TLIP) block was recently described as a regional anesthetic technique to achieve analgesia for lumbar spine surgery by blocking the dorsal rami of spinal nerves. The study aims to test the hypothesis that TLIP block can offer pain control and reduce the perioperative analgesic requirement in patients undergoing spinal surgery. There were 60 patients scheduled for lumbar spine surgery who were randomly assigned into two equal groups, TLIP and control groups. Patients in the TLIP group received general anesthesia and TLIP block while patients in the control group received general anesthesia alone. The primary outcome was the analgesic consumption in the first postoperative 24 hours, while intraoperative additional analgesic needs, time to the first request of postoperative analgesia, and pain scores were the secondary outcomes. At 24 hours postoperatively, morphine consumption was lower in the TLIP group (5.13±1.55) versus the control group (14.33±2.58) mg. The intraoperative fentanyl consumption was lower in the TLIP group (15±35.11 mcgs) versus the control group (105±62.08 mcgs). Postoperative first request for analgesia was delayed in the TLIP group (7.30±2.69 h) compared to the control group (0.92±1.23 h). Postoperative Pain scores at rest were 2.53 ± 0.97 and 3.43 ± 0.50 at 24 hours in the TLIP group and the control group, respectively. Postoperative Pain scores at passive flexion of spine were 2.73 ±0.87 and 3.93 ±0.78 at 24 hours in the TLIP group and the control group, respectively. Patients in the TLIP group had lower perioperative hemodynamic responses to surgical stimulation in comparison to the control group. Combined TLIP block with general anesthesia in patients undergoing spinal surgery reduced both postoperative and intraoperative analgesic needs, reduced intra-operative hemodynamic response to surgery, and achieved good postoperative pain control.

Dual targeting of epidermal growth factor receptor (EGFR) and human EGFR-related receptor 2 (HER2) is a proven approach for the treatment of lung cancer. With the aim of discovering effective dual EGFR/HER2 inhibitors targeting non-small cell lung cancer cell line H1299, three series of thieno[2,3-d][1,2,3]triazine and acetamide derivatives were designed, synthesized, and biologically evaluated. The synthesized compounds displayed IC50 values ranging from 12 to 54 nM against H1299, which were superior to that of gefitinib (2) at 40 µM. Of the synthesized compounds, 2-(1H-pyrazolo[3,4-b]pyridin-3-ylamino)-N-(3-cyano4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)acetamide (21a) achieved the highest in vitro cytotoxic activity against H1299, with an IC50 value of 12.5 nM in situ, and 0.47 and 0.14 nM against EGFR and HER2, respectively, values comparable to the IC50 of the approved drug imatinib (1). Our synthesized compounds were promising, demonstrating high selectivity and affinity for EGFR/HER2, especially the hinge region forming a hydrophobic pocket, which was mediated by hydrogen bonding as well as hydrophobic and electrostatic interactions, as indicated by molecular modeling. Moreover, the designed compounds showed good affinity for T790M EGFR, one of the main mutants resulting in acquired drug resistance. Furthermore, both pharmacokinetic and physicochemical properties of the designed compounds were within the appropriate range for human usage as predicted by the in Silico ADME study. The designed compound (21a) might serve as an encouraging lead compound for the discovery of promising anti-lung cancer agents targeting EGFR/HER2.

The effects of fipronil (FPN) on the liver of rats were studied. Rats ( n  = 6) were treated with 9.7 mg/kg (1/10 of FPN LD 50 ), and other rats ( n  = 6) received 120 mg/kg of 10% Uncaria tomentosa extract, while a mixture of 9.7 mg/kg FPN and 120 mg/kg of 10% Uncaria tomentosa extract were administered orally to the rats ( n  = 6) daily for 6 weeks. Body, hepatic weights, liver enzymes, and lipid profile were determined. Hepatic activities of MDA, TNO, TAC, TNF-α, and IL-6 in liver homogenate were measured. Immunohistochemistry of NF-kB and liver histopathology were performed. Fipronil-treated rats had a significant ( P  = 0.02) lower weight gain. Moreover, relative liver weight was significantly ( P  = 0.003) increased in FPN-treated rats. Rats administrated with FPN exhibited a significantly ( P  = 0.02) higher liver enzymes and promoted levels of MDA, TNO, TNF-α, and IL-6 ( P  < 0.0001) than that in the other groups. Immunostaining of NF-κB was increased ( P  < 0.0001) in FPN-treated rats. Interestingly, Uncaria tomentosa alone or with FPN decreased the liver immunostaining of NF-κB. In conclusion, FPN produced liver injury through lipid peroxidation and stimulation of NF-κB. However, Uncaria tomentosa combated the oxidative stress and liver damage induced by FPN via inhibition of NF-κB.

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

Summary The discovery of potent antidiabetic drugs is of necessity owing to the rapid prevalence of diabetes worldwide. The investigation of a new separation method for the simultaneous determination of combined antidiabetic drugs is thus an essential issue to cover the usual demands of simple analytical methods for the routine analysis. Therefore, herein, simple and fast chromatographic methods were established for synchronized determination of metformin (MET) and dapagliflozin (DAP), a mixture approved recently by the Food and Drug Administration (FDA) for diabetes therapy. In high-performance liquid chromatography (HPLC), a Water-pak C18 column was used as the stationary phase with an isocratic mobile phase composed of 10 mM NaH 2 PO 4 (pH 3.5 adjusted using ortho -phosphoric acid)—acetonitrile (65:35, v / v ) containing 0.1% trimethylamine at a flow rate of 1.2 mL min −1 and a wavelength detector set at 225 nm. In high-performance thin-layer chromatography (HPTLC), separation was achieved on pre-coated silica gel 60 F 254 aluminum plates using acetonitrile—ammonium acetate 10%—acetic acid (9:0.9:0.1, v / v ). The proposed methods were validated in the light of the International Conference on Harmonization (ICH) guidelines, and it was found that the two chromatographic methods are accurate, precise, and linear in the range of 2–20 µg mL −1 and 1–10 µg per spot for DAP and 20–400 µg mL −1 and 10–100 µg per spot for MET by HPLC and HPTLC, respectively. The methods achieved a reasonable sensitivity as shown by the low limit of detection ranging from 0.58 to 6.1 µg mL −1 and 0.314 to 3.1 µg per spot for HPLC and HPTLC, respectively. The validated methods succeeded in detecting the cited drugs in pharmaceutical formulation without interference of excipients. Although HPLC method is the most applicable method, HPTLC method exhibits a superior sensitivity and is cheap and fast allowing the determination of a large number of samples in due time.

This study was conducted to elucidate the ameliorative potential of lycopene (LYC) against the metabolic toxicity induced by bisphenol A (BPA) in rats. Male rats ( n  = 28) were divided into 4 equal groups: control group, LYC group was given lycopene (10 mg/kg BW), BPA group was given 10 mg/kg BW of BPA, and the last group was administered BPA and LYC at 10 mg/kg via gavage for 90 consecutive days. Body weight (BW) gain, lipid profile, and total antioxidant capacity (TAC) were assessed. Oral glucose tolerance test (OGTT), homeostasis model assessment–estimated insulin resistance (HOMA-IR), thyroid hormones, interleukin-1 beta (IL-1β), leptin, and resistin were assayed. Moreover, immunohistochemistry of TNF-α was performed in adipose tissue. BPA-treated rats showed significant reduction in BW gain and deteriorations in lipid profile, TAC, OGTT, and thyroid hormones as well as significant increases in HOMA-IR, IL-1β, leptin, and resistin. While, improvement of metabolic parameters was observed when LYC was administrated with BPA. Intense TNF-α immunostaining was detected in the fat of BPA-treated rats but the intensity decreased when LYC was administrated with BPA. In conclusion, LYC ameliorated the adverse effects of BPA on metabolism through its antioxidant potential and its reduction of TNF-α expression in adipose tissue.