Thioacetamide (TAA)-induced liver fibrosis, triggered by inflammation and oxidative stress, is prompted by hepatic stellate cells (HSCs) activation via several pathways. This study explores the hepatoprotective effect of aloe vera gel (AVG) extract and bone marrow mesenchymal stem cells (BM-MSCs) transplantation on regulating long intergenic noncoding RNA (lincRNA-p21) and microRNA (miR-17-5p) expressions and their impact on TGF-β1/Smad-3 and Wnt-10a/ β-Catenin cascades in TAA-induced liver damage. The study involved 48 adult male albino rats divided into four groups:control, TAA, TAA treated with BM-MSCs, and TAA treated with BM-MSCs+AVG extract. After 8 weeks, liver enzymes and hepatic oxidative parameters were evaluated alongside lincRNA-p21, miR-17-5p, TGF-β1, Smad-3, Wnt-10a, and β-Catenin expressions. Liver tissue sections were examined by light and electron microscopes and analyzed morphometrically. Group II showed increased aspartate aminotransferase, alanine aminotransferase, malondialdehyde, reduced glutathione levels, and deteriorated hepatocytes with distorted mitochondria and dilated rough endoplasmic reticulum. Group IV restored lincRNA-p21 expression, which downregulated miR-17-5p and suppressed activated HSCs by inhibiting TGF-β1/Smad-3 and Wnt-10a/β-Catenin pathways, and improved hepatic tissue architecture. Additionally, immunohistochemically, alpha-smooth muscle actin and cyclin D1 expressions were markedly decreased in group IV compared to group II. We concluded that AVG suppresses fibrotic pathways, boosts BM-MSCs differentiation, and reduces HSCs activation in liver fibrosis caused by TAA.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Purpose: Curcumin as a potent anti-inflammatory and cancer-prevention molecule was labeled with n.c.a 177Lu. The combi-nation of 177Lu as a theranostic agent and curcumin as an anti-cancer can be considered for nuclear medicine. Methods: First, n.c.a 177Lu (specific activity = 48 Ci/mg) was prepared using the extraction chromatography method. Then,semi-empirical quantum chemical calculations were applied to get a deeper insight into the complexation reaction between Lu+3 and curcumin ligand. UV-Vis spectrophotometry was used for the determination of the metal-to-curcumin ratio. Sub-sequently, a mixture of (111–333 MBq) n.c.a 177Lu, 50 µL curcumin solution in ethanol, and 450 µL acetate buffer at pH = 5was incubated for 1  h at 95 ºC. The Lu-curcumin complex chemical structure was characterized using IR spectroscopy.Finally, the prepared complex was analyzed by different quality control tests. Results: Complexometry using UV-Vis studies showed a 1:2 ratio for Lutetium: curcumin complex which is in agreement with theoretical calculations. The IR-spectra analysis also confirmed the complex formation. The radiochemical purity of n.c.a 177Lu -curcumin was more than 95% as determined by radio-TLC. The stability of up to 48 h was observed for theprepared complex in serum. The partition coefficient was calculated for the compound (logP = -0.31). Evaluating biodistri-bution in tumoral mice exhibited high tumor uptake (%ID/gtissue = 2.03). Conclusion The promising results showed that n.c.a 177Lu-curcumin can be considered as a possible radiopharmaceutical agent for therapeutic applications.

Background: Post-dural puncture headache (PDPH) is one of the most common complications in patients undergoing spinal anesthesia. The present systematic review and meta-analysis aimed to assess the therapeutic and prophylactic effects of aminophylline and theophylline on PDPH. Methods: Relevant studies were identified by searching the following electronic databases, without language restriction, until June 2020: Scopus, EMBASE, MEDLINE, Google Scholar, Web of Science, Cochrane Library-CENTRAL, and CINAHL Complete. Random effects models were used to calculate the standardized mean difference (SMD) and risk ratios (RRs) with 95% confidence intervals (95% CI) to assess the therapeutic and prophylactic effects of aminophylline and theophylline on PDPH, respectively. The Cochrane tool was used for the quality assessment of the included studies. The certainty of the evidence was rated using the Grading of Recommendations Assessment, Development, and Evaluation method. Results: Of the 1,349 initial records, 15 met our eligibility criteria (6 studies on therapeutic and 9 on prophylactic effects). A significant reduction in the pain score was observed following aminophylline/theophylline treatment (SMD = –1.67; 95% CI, –2.28 to –1.05; P < 0.001, I2 = 84.7%; P < 0.001). Subgroup analysis revealed that the therapeutic effect was significantly higher when these agents were compared to placebo than when conventional therapies were used. The risk of PDPH after aminophylline administration was not significantly reduced (RR = 0.74; 95% CI, 0.42 to 1.31; P = 0.290). Conclusions Theophylline and aminophylline have therapeutic, but not prophylactic, effects on PDPH.

Drug resistance is a great challenge in cancer therapy using chemotherapeutic agents.Administration of these drugs with siRNA is an efficacious strategy in this battle.Here,the present study tried to incor-porate siRNA and paclitaxel(PTX)simultaneously into a novel nanocarrier.The selectivity of carrier to target cancer tissues was optimized through conjugation of folic acid(FA)and glucose(Glu)onto its surface.The structure of nanocarrier was formed from ternary magnetic copolymers based on FeCo-polyethyleneimine(FeCo-PEI)nanoparticles and polylactic acid-polyethylene glycol(PLA-PEG)gene delivery system.Biocompatibility of FeCo-PEI-PLA-PEG-FA(NPsA),FeCo-PEI-PLA-PEG-Glu(NPsB)and FeCo-PEI-PLA-PEG-FA/Glu(NPsAB)nanoparticles and also influence of PTX-loaded nanoparticles on in vitro cytotoxicity were examined using MTT assay.Besides,siRNA-FAM internalization was investi-gated by fluorescence microscopy.The results showed the blank nanoparticles were significantly less cytotoxic at various concentrations.Meanwhile,siRNA-FAM/PTX encapsulated nanoparticles exhibited significant anticancer activity against MCF-7 and BT-474cell lines.NPsAB/siRNA/PTX nanoparticles showed greater effects on MCF-7 and BT-474 cells viability than NPsA/siRNA/PTX and NPsB/siRNA/PTX.Also,they induced significantly higher anticancer effects on cancer cells compared with NPsA/siRNA/PTX and NPsB/siRNA/PTX due to their multi-targeted properties using FA and Glu.We concluded that NPsAB nanoparticles have a great potential for co-delivery of both drugs and genes for use in gene therapy and chemotherapy.

BACKGROUND: Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects oftherapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to humanhepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and thepresence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this studywas to generate the scalable and functional hepatic micro-tissues (HMTs). METHODS: The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cellsand human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, usingan air-driven droplet generator. RESULTS: The generated HMTs were functional throughout a culture period of 28 days, as assessed by monitoringglycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretionlevels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involvedin hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional(2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity tohepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450enzymes confirmed that the HMTs can be used for in vitro drug screening. CONCLUSION Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7,with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.

BACKGROUND: Currently, there is an urgent need for scalable and reliable in vitro models to assess the effects oftherapeutic entities on the human liver. Hepatoma cell lines, including Huh-7, show weakly resemblance to humanhepatocytes, limiting their significance in toxicity studies. Co-culture of hepatic cells with non-parenchymal cells, and thepresence of extracellular matrix have been shown to influence the biological behavior of hepatocytes. The aim of this studywas to generate the scalable and functional hepatic micro-tissues (HMTs). METHODS: The size-controllable HMTs were generated through co-culturing of Huh-7 cells by mesenchymal stem cellsand human umbilical vein endothelial cells in a composite hydrogel of liver-derived extracellular matrix and alginate, usingan air-driven droplet generator. RESULTS: The generated HMTs were functional throughout a culture period of 28 days, as assessed by monitoringglycogen storage, uptake of low-density lipoprotein and indocyanine green. The HMTs also showed increased secretionlevels of albumin, alpha-1-antitrypsin, and fibrinogen, and production of urea. Evaluating the expression of genes involvedin hepatic-specific and drug metabolism functions indicated a significant improvement in HMTs compared to two-dimensional(2D) culture of Huh-7 cells. Moreover, in drug testing assessments, HMTs showed higher sensitivity tohepatotoxins compared to 2D cultured Huh-7 cells. Furthermore, induction and inhibition potency of cytochrome P450enzymes confirmed that the HMTs can be used for in vitro drug screening. CONCLUSION Overall, we developed a simple and scalable method for generation of liver micro-tissues, using Huh-7,with improved hepatic-specific functionality, which may represent a biologically relevant platform for drug studies.