Objective: Interferon (IFN) signaling, and excessive apoptosis have a well-established role in systemic lupus erythematosus (SLE) pathogenesis. Long non-coding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) has been linked to excessive apoptosis and upregulation of IFN genes. We aimed to investigate the expression of IFN-stimulated genes in SLE patients compared to healthy controls, and to assess their association with lncRNA GAS5 and clinical characteristics of SLE. Methods: The study included 30 SLE patients and 20 controls. IFN-stimulatory genes (interferon-induced protein 44-like [IFI44L] gene, MX dynamin like GTPase 1 [MX1], IFN-induced protein with tetratricopeptide repeats 1 [IFIT1]) and GAS5 expression levels in plasma were estimated by quantitative real-time polymerase chain reaction. IFN signature score was calculated. Results: IFIT1 gene expression and IFN signature score were significantly higher in SLE patients compared to controls (p<0.001, p<0.001, respectively). LncRNA GAS5 positively correlated with IFIT1 expression (p<0.001) and IFN signature score (p=0.005).No significant associations were found between IFN gene expression or IFN signature score and disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2K) or organ damage (Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index, SDI). IFI44L expression was significantly higher in SLE patients with secondary antiphospholipid syndrome (p=0.040). Conclusion IFN signature is a potential biomarker for SLE diagnosis, but it can’t be relied on for the assessment of activity or damage. The correlation between lncRNA GAS5 and IFN-related gene expression suggests a possible role for GAS5 in the IFN pathway in SLE.

Aberrant CXCR4/CXCL12 signaling is involved in many pathophysiological processes such as cancer and inflammatory diseases. A natural fragment of serum albumin, named EPI-X4, has previously been identified as endogenous peptide antagonist and inverse agonist of CXCR4 and is a promising compound for the development of improved analogues for the therapy of CXCR4-associated diseases. To generate optimized EPI-X4 derivatives we here performed molecular docking analysis to identify key interaction motifs of EPI-X4/CXCR4. Subsequent rational drug design allowed to increase the anti-CXCR4 activity of EPI-X4. The EPI-X4 derivative JM#21 bound CXCR4 and suppressed CXCR4-tropic HIV-1 infection more efficiently than the clinically approved small molecule CXCR4 antagonist AMD3100. EPI-X4 JM#21 did not exert toxic effects in zebrafish embryos and suppressed allergen-induced infiltration of eosinophils and other immune cells into the airways of animals in an asthma mouse model. Moreover, topical administration of the optimized EPI-X4 derivative efficiently prevented inflammation of the skin in a mouse model of atopic dermatitis. Thus, rationally designed EPI-X4 JM#21 is a novel potent antagonist of CXCR4 and the first CXCR4 inhibitor with therapeutic efficacy in atopic dermatitis. Further clinical development of this new class of CXCR4 antagonists for the therapy of atopic dermatitis, asthma and other CXCR4-associated diseases is highly warranted.

Introduction: Tibia is the most common long bone fractured due its vulnerable subcutaneous location and most often associated with acquired complications of delayed union or non-union due to infection. Amongst the various treatment options to treat them, the Ilizarov external fixator application is considered superior due to its multiple advantages. The objective of this study was to analyse the role of Ilizarov fixation in infected tibial non-union, as well as to assess bony union and associated functional outcomes. Materials and Methods: A retrospective review was conducted for the duration between 1st January 2005 to 31st December 2016. Total of fifty-one patients with tibial non-union associated with infection who treated with the Ilizarov fixator were included in the study. Patient records were reviewed for union of bone, bone and functional outcomes and complications. Results:The most common organism for infection was identified to be Staphylococcus Aureus. At the time of final follow-up all patients had achieved union except two, one of whom had to undergo amputation due to non-union and sepsis. Majority of the patients had an excellent score as per ASAMI grading system for bone and function results. The most common complication noted was pin track infections. Conclusion: In our experience, Ilizarov external fixator is better suited for infected non-union of tibia because it can provide a stable mechanical environment, bone transport, correct deformities, and enable weight bearing and hence we recommend its use for the same.

BACKGROUND/AIMS: Food bolus impaction is the most common form of esophageal foreign body impaction observed in adults. Clinical guidelines recommend using the push technique or retrieval methods in such cases. The push technique can cause injuries in certain clinical situations. Notably, conventional retrieval methods are time and effort consuming. Cap-assisted endoscopic extraction of an impacted food bolus is an easy and effective technique; however, more data are needed for its validation. This study compared the capassisted extraction technique with conventional methods. METHODS: This prospective observational multicenter study compared the success and en bloc removal rates, total procedure time, and adverse events in both techniques.. RESULTS: The study included 303 patients who underwent food bolus extraction. The push technique was used in 87 patients (28.7%) and a retrieval procedure in 216 patients (71.3%). Cap-assisted extraction was performed in 106 patients and retrieval using conventional methods in 110 patients. The cap-assisted technique was associated with a higher rate of en bloc removal (80.2% vs. 15%, p<0.01), shorter procedure time (6.9±3.5 min vs. 15.7±4.1 min, p<0.001), and fewer adverse events (0/106 vs. 9/110, p<0.001). CONCLUSIONS: Cap-assisted extraction showed no adverse events, higher efficacy, and a shorter procedure time compared with conventional retrieval procedures.
Adult ; Foreign Bodies ; Humans ; Methods ; Prospective Studies

Objective: To assess the antiangiogenic activity of fenugreek. Methods: Different fractions of fenugreek crude extracts were prepared and their anti-angiogenic properties were assessed using the ex vivo rat aortic ring assay and in vivo chicken embryo chorioallantoic membrane (CAM) assay. They were investigated for their direct cytotoxic activity in the MCF7 cells using the MTT assay. Results: The ethanol extract showed 100％ inhibition of blood vessel outgrowth from primary tissue explants in the rat aortic ring assay at a concentration of 100μg/mL while the other extracts did not show significant antiangiogenic activity. The ethanol extract was therefore investigated at varying concentrations and exhibited a significant dose dependent effect. The CAM assay coincided with the results of the aortic ring assay as ethanol extract showed a significant inhibition of formation of new blood vessels. The extracts only showed anti-proliferative activity at the highest concentration of 400μg/mL towards MCF7 breast cancer cell lines in the MTT assay. Conclusions: Findings of the both assays confirmed that the ethanol extract inhibited vascularization significantly. Further studies on the ethanol extract would be beneficial in isolating the active ingredient responsible for the inhibition.

Objective To assess the antiangiogenic activity of fenugreek. Methods Different fractions of fenugreek crude extracts were prepared and their antiangiogenic properties were assessed using the ex vivo rat aortic ring assay and in vivo chicken embryo chorioallantoic membrane (CAM) assay. They were investigated for their direct cytotoxic activity in the MCF7 cells using the MTT assay. Results The ethanol extract showed 100% inhibition of blood vessel outgrowth from primary tissue explants in the rat aortic ring assay at a concentration of 100 μg/mL while the other extracts did not show significant antiangiogenic activity. The ethanol extract was therefore investigated at varying concentrations and exhibited a significant dose dependent effect. The CAM assay coincided with the results of the aortic ring assay as ethanol extract showed a significant inhibition of formation of new blood vessels. The extracts only showed anti-proliferative activity at the highest concentration of 400 μg/mL towards MCF7 breast cancer cell lines in the MTT assay. Conclusions Findings of the both assays confirmed that the ethanol extract inhibited vascularization significantly. Further studies on the ethanol extract would be beneficial in isolating the active ingredient responsible for the inhibition.

OBJECTIVETo investigate mosquitocidal effects of ethanolic extract of flowers of Tagetes erecta (T. erecta) and its chloroform and petroleum ether soluble fractions against the larvae of Culex quinquefasciatus (Cx. quinquefasciatus).

METHODSThe fresh flowers of T. erecta were extracted in cold with ethanol (5.0 L) and after concentration, the ethanol extract was fractionated with chloroform and petroleum ether to afford a brownish syrupy suspension of ethanol extract (50.0 g), petroleum ether soluble fraction (18.6 g) and chloroform soluble fraction (23.8 g). The larvicidal effect of ethanol extract and their solvent fractions were determined by the standard procedure of WHO against different instars of Cx. quinquefasciatus.

RESULTSAmong the tested samples the chloroform soluble fractions showed the highest toxicity and consequently, the lowest LC50 values (14.14 µg/mL, 17.06 µg/mL, 36.88 µg/mL and 75.48 µg/mL) for all the instars larvae of Cx. quinquefasciatus. The larvae showed comparative tolerance in the course of increasing age and time.

CONCLUSIONSIt can be concluded that the flowers of T. erecta are very effective natural larvicide and could be useful against Cx. quinquefasciatus.

Animals ; Culex ; drug effects ; Flowers ; chemistry ; Insecticides ; pharmacology ; Lethal Dose 50 ; Parasitic Sensitivity Tests ; Plant Extracts ; pharmacology ; Tagetes ; chemistry

OBJECTIVETo evaluate the antitumor activity of Manilkara zapota (M. zapota) L. stem bark against Ehrlich ascites carcinoma (EAC) in Swiss albino mice.

METHODSThe in vivo antitumour activity of the ethyl acetate extract of stem bark of M. zapota L. (EASM) was evaluated at 50, 100 and 200 mg/kg bw against EAC using mean survival time. After administration of the extract of M. zapota, viable EAC cell count and body weight in the EAC tumour hosts were observed. The animal was also observed for improvement in the haematological parameters (e.g., heamoglobin content, red and white blood cells count and differential cell count) after EASM treatment.

RESULTSIntraperitoneal administration of EASM reduced viable EAC cells, increased the survival time, and restored altered haematological parameters. Significant efficacy was observed for EASM at 100 mg/kg dose (P<0.05).

CONCLUSIONSIt can be concluded that the ethyl acetate extract of stem bark of M. zapota L. possesses significant antitumour activity.

Animals ; Antineoplastic Agents ; isolation & purification ; therapeutic use ; Body Weight ; Carcinoma, Ehrlich Tumor ; drug therapy ; Cell Survival ; drug effects ; Disease Models, Animal ; Injections, Intraperitoneal ; Male ; Manilkara ; chemistry ; Mice ; Plant Bark ; chemistry ; Plant Extracts ; isolation & purification ; therapeutic use ; Survival Analysis ; Treatment Outcome