Pathologic response evaluation of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy: a clinical trial.

Objective: Esophageal cancer is a therapeutic challenge in most healthcare systems. Most patients present with locally advanced disease at diagnosis. Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced esophageal carcinoma. Since achieving a complete pathological response in postoperative specimens following neoadjuvant therapy is associated with improved patient survival, this study was designed to evaluate the pathologic response of localized or locally advanced esophageal carcinoma to induction chemotherapy followed by preoperative concurrent chemotherapy and hypofractionated radiotherapy (HFR). Methods: This single-arm clinical trial (IRCT20210623051676N1) evaluated patients with squamous cell carcinoma or adenocarcinoma of the esophagus, stage cT2-T4a N0 M0 or cT1-T4a N+ M0. Patients received 3-5 cycles of weekly induction chemotherapy with the paclitaxel (50 mg/m2) and carboplatin (AUC=2) regimen, followed by weekly concurrent CRT with the same chemotherapy regimen. The radiation dose was 40 Gy, delivered over 16 fractions, 5 days per week (2.5 Gray/fraction). Patients underwent surgery 4-6 weeks after completion of CRT. The surgical specimens were evaluated for pathological response. A p-value of < 0.05 was considered significant in all analyses. Results: Out of 54 patients enrolled in this study, 45 completed the neoadjuvant protocol. Of these 45 patients, 32 underwent surgery and were finally analyzed. The mean age of the patients was 59.9 ± 8.6 years (range, 37-75 years). The location of the tumor was in the mid-thoracic esophagus in most patients (21, 65.6%) and the most common histological type was SCC (29, 90.6%). The median number of induction and concurrent chemotherapy cycles was 5 (4.8 ± 1.3 course, range, 1-10) and 3 (2.6 ± 0.8 course, range, 0-4), respectively. Among 45 patients who completed the neoadjuvant protocol, the most common toxicities were grade 3 neutropenia (15.6%), acute renal failure (4.4%), and odynophagia (37.8%). Nearly two-thirds of the patients experienced complete or near-complete responses (71.9%, 23 patients). Partial response was reported in 6 patients (18.8%) and poor response in 3 patients (9.4%). Conclusion: Preoperative induction chemotherapy followed by HFR with concurrent chemotherapy has low toxicity and side effects, good tolerance, and significant efficacy in the treatment of patients with esophageal cancer. Clinical trial registration: https://irct.behdasht.gov.ir/trial/59930, identifier NCT05745545.

Safety evaluation of the trastuzumab biosimilar in Iranian women with HER2-positive breast cancer undergoing adjuvant chemotherapy: a post-marketing surveillance.

BACKGROUND: Trastuzumab is a humanized monoclonal antibody against the human epidermal growth factor receptor 2 (HER2). This post-marketing surveillance evaluates the safety of a trastuzumab biosimilar (AryoTrust), produced by AryoGen Co. Iran in Iranian women with HER2-positive non-metastatic breast cancer (BC). RESEARCH DESIGN AND METHODS: The patients who had undergone adjuvant chemotherapy regimens received trastuzumab every 3 weeks for nine cycles. The study started in February 2017 and finished in August 2022. Data regarding safety were collected using booklets and then analyzed. RESULTS: A total of 597 women with a mean ±SD age of 48.13 ± 10.18 years underwent 5,313 injection cycles. They received pre-study chemotherapies consisting of anthracyclines, taxanes, both, or other medications in 6.70, 7.20, 82.41, and 2.01% of the cases, respectively. One hundred and thirty-nine patients experienced at least one adverse event (AE). The most common AEs were decreased ejection fraction (EF, 5.7%), peripheral neuropathy (5.36%), and nausea (5.19%). Meningioma was the only life-threatening serious AE. Furthermore, bone pain and infusion-related reactions were the two most common grade three AEs. Nevertheless, the mean EF of patients did not change notably during the study. CONCLUSIONS: The results demonstrate that this trastuzumab biosimilar is a generally well tolerated and safe treatment for HER2-positive BC. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT06021379.

Structural basis of human NOX5 activation.

NADPH oxidase 5 (NOX5) catalyzes the production of superoxide free radicals and regulates physiological processes from sperm motility to cardiac rhythm. Overexpression of NOX5 leads to cancers, diabetes, and cardiovascular diseases. NOX5 is activated by intracellular calcium signaling, but the underlying molecular mechanism of which - in particular, how calcium triggers electron transfer from NADPH to FAD - is still unclear. Here we capture motions of full-length human NOX5 upon calcium binding using single-particle cryogenic electron microscopy (cryo-EM). By combining biochemistry, mutagenesis analyses, and molecular dynamics (MD) simulations, we decode the molecular basis of NOX5 activation and electron transfer. We find that calcium binding to the EF-hand domain increases NADPH dynamics, permitting electron transfer between NADPH and FAD and superoxide production. Our structural findings also uncover a zinc-binding motif that is important for NOX5 stability and enzymatic activity, revealing modulation mechanisms of reactive oxygen species (ROS) production.

Comparing the effect of sexual counseling based on BETTER and PLISSIT models on sexual assertiveness in women with breast cancer after mastectomy.

BACKGROUND: Sexual changes in breast cancer occur after diagnosis and treatment, including a mastectomy. Sexual assertiveness is an effective factor in sexual satisfaction, which means the ability to convey sexual feelings, beliefs, and thoughts. Given the limited studies on sexual assertiveness in breast cancer and different client participation, this study was conducted to compare the effect of sexual counseling based on two models of PLISSIT (Permission, Limited Information, Specific Suggestion, Intensive Therapy) and BETTER (Bring Up, Explain, Tell, Time, Education, Record) on sexual assertiveness in women after mastectomy. MATERIALS AND METHODS: This quasi-experimental intervention was conducted in 2021 in Mashhad, Iran. Seventy-eight mastectomized women with breast cancer were assigned to the BETTER (n = 39) and PLISSIT (n = 39) groups using permuted block randomization with a block size of 4 and an allocation ratio of 1:1. Both groups received four individual counseling sessions, one week apart. The research tools included a demographic information form and the Hulbert index of sexual assertiveness. Changes in the mean scores of sexual assertiveness between the two groups were evaluated before and four weeks after the intervention, and the mean changes were compared between the groups. Data analysis was conducted using the Kolmogorov-Smirnov test, independent t-test, paired t-test, and Chi-square tests using Statistical Package for the Social Sciences (SPSS) version 25 (P < 0.05). RESULTS: The results of the study showed that before the intervention, there was no significant difference in the score of sexual assertiveness in both groups (P = 0.253). The mean score of sexual assertiveness changes before and after the intervention in the BETTER group (8.07 ± 4.9) was significantly higher than in the PLISSIT group (5.58 ± 4.7) (P < 0.001). CONCLUSION: The results indicated that BETTER sexual counseling was more effective in increasing the sexual assertiveness of mastectomized women than PLISSIT counseling. Due to its simplicity and client-centeredness, this model can be used in breast cancer care programs.

Unveiling the structure-emulsifying function relationship of truncated recombinant forms of the SA01-OmpA protein opens up a new vista in bioemulsifiers.

The emulsifying ability of SA01-OmpA (outer membrane protein A from Acinetobacter sp. SA01) was found to be constrained by challenges like low production efficiency and high costs associated with protein recovery from E. coli inclusion bodies, as described in our previous study. The present study sought to benefit from the advantages of the targeted truncating of SA01-OmpA protein, taking into account the reduced propensity of protein expression as inclusion bodies and cytotoxicity. Here, the structure and activity relationship of two truncated recombinant forms of SA01-OmpA protein was unraveled through a hybrid approach based on experimental data and computational methodologies, representing an innovative bioemulsifier with advantageous emulsifying activity. The recombinant truncated SA01-OmpA variants were cloned and heterologously expressed in E. coli host cells and subsequently purified. The results showed increased emulsifying activity of N-terminally truncated SA01-OmpA (NT-OmpA) compared to full-length SA01-OmpA. Molecular dynamics (MD) simulations analysis demonstrated a direct correlation between the C-terminally truncated SA01-OmpA (CT-OmpA) and its expression as inclusion bodies. Analysis of the structure-activity relationship of truncated variants of SA01-OmpA revealed that, compared to the full-length protein, deletion of the ß-barrel portion from the N-terminal of SA01-OmpA increased the emulsifying activity of NT-OmpA while lowering its expression as inclusion bodies. Contrary to the full-length protein, the N-terminally truncated SA01-OmpA was not as cytotoxic, according to the MTT assay, FCM analysis, and AO/EB staining. The findings of this extensive study advance our knowledge of SA01-OmpA at the molecular level as well as the design and development of efficient bioemulsifiers.IMPORTANCEPrevious research (Shahryari et al. 2021, mSystems 6: e01175-20) introduced and characterized the SA01-OmpA protein as a multifaceted protein with a variety of functions, including maintaining cellular homeostasis under oxidative stress conditions, biofilm formation, outer membrane vesicles (OMV) biogenesis, and beneficial emulsifying capacity. By truncating the SA01-OmpA protein, the current study presents a unique method for developing protein-type bioemulsifiers. The findings indicate that the N-terminally truncated SA01-OmpA (NT-OmpA) has the potential to fully replace full-length SA01-OmpA as a novel bioemulsifier with significant emulsifying activity. This study opens up a new frontier in bioemulsifiers, shedding light on a possible relationship between the structure and activity of SA01-OmpA truncated forms.

GproteinDb in 2024: new G protein-GPCR couplings, AlphaFold2-multimer models and interface interactions.

G proteins are the major signal proteins of ∼800 receptors for medicines, hormones, neurotransmitters, tastants and odorants. GproteinDb offers integrated genomic, structural, and pharmacological data and tools for analysis, visualization and experiment design. Here, we present the first major update of GproteinDb greatly expanding its coupling data and structural templates, adding AlphaFold2 structure models of GPCR-G protein complexes and advancing the interactive analysis tools for their interfaces underlying coupling selectivity. We present insights on coupling agreement across datasets and parameters, including constitutive activity, agonist-induced activity and kinetics. GproteinDb is accessible at https://gproteindb.org.

Economical Evaluation of Prostate Cancer Treatment Using Intensity-Modulated Radiation Therapy, 3-Dimensional Conformal Radiation Therapy and Radical Prostatectomy: A Systematic Review.

OBJECTIVES: Prostate cancer is a common form of cancer among men worldwide. The objective of this study was to conduct a systematic review of the economic evaluations of prostate cancer treatment strategies. METHODS: This systematic review was conducted using multiple electronic databases up to May 2021. English-language economic evaluation studies that compared intensity-modulated radiation therapy (IMRT), 3-dimensional conformal radiation therapy (3DCRT), and radical prostatectomy (RP) were included. The studies were evaluated using the Consolidated Health Economic Evaluation Reporting Standards checklist. The search yielded 1151 potentially relevant publications, which were screened based on the title and abstract. After the removal of duplicates, 55 studies remained, and 9 studies were screened in full text. Finally, textual data were analyzed manually using by-content analysis method. RESULTS: All studies were cost-effective and evaluated quality-adjusted life year as the efficacy indicator. The studies were conducted from either payers' or health systems' perspectives, and the time horizon varied from 5 to 20 years. We included only full economic evaluation studies. The use of IMRT in comparison with 3DCRT was evaluated in 6 studies, based on which IMRT increased health and reduced side effects of treatment. According to incremental cost-effectiveness ratio (ICER) results, IMRT was more cost-effective than 3DCRT. Three studies evaluated the use of RP in comparison with radiotherapy. Based on these studies, radiotherapy was more effective than RP. CONCLUSION: IMRT was found to be more cost-effective than 3DCRT in all 6 studies compared with the threshold. Radiotherapy was found to be more effective than RP. However, long-term clinical trial studies are needed to confirm these findings and to provide more definitive conclusions.

Applications of fluorescent protein tagging in structural studies of membrane proteins.

Generating active, pure, and monodisperse protein remains a major bottleneck for structural studies using X-ray crystallography and cryo-electron microscopy (cryo-EM). The current methodology heavily relies on overexpressing the recombinant protein fused with a histidine tag in conventional expression systems and evaluating the quality and stability of purified protein using size exclusion chromatography (SEC). This requires a large amount of protein and can be highly laborious and time consuming. Therefore, this approach is not suitable for high-throughput screening and low-expressing macromolecules, particularly eukaryotic membrane proteins. Using fluorescent proteins fused to the target protein (applicable to both soluble and membrane proteins) enables rapid and efficient screening of expression level and monodispersity of tens of unpurified constructs using fluorescence-based size exclusion chromatography (FSEC). Moreover, FSEC proves valuable for screening multiple detergents to identify the most stabilizing agent in the case of membrane proteins. Additionally, FSEC can facilitate nanodisc reconstitution by determining the optimal ratio of membrane scaffold protein (MSP), lipids, and target protein. The distinct advantages offered by FSEC indicate that fluorescent proteins can serve as a viable alternative to commonly used affinity tags for both characterization and purification purposes. In this review, I will summarize the advantages of this technique using examples from my own work. It should be noted that this article is not intended to provide an exhaustive review of all available literature, but rather to offer representative examples of FSEC applications.

A nested variant of urothelial carcinoma of the urethra and urinary bladder: A case report and review of literature.

Nested variant of urothelial carcinoma (NV-UC) is an extremely rare cancer with a nonspecific presentation. It is usually identified at a late stage, which makes the treatment challenging. Herein we report the case of a 52-year-old woman with an advanced NV-UC treated by anterior exenteration after a poor response to neoadjuvant chemotherapy. One year after completion of adjuvant radiotherapy, the patient remains disease-free.

Leiomyosarcoma, a rare smooth muscle cancer in the pancreas: An adjuvant radiotherapy treatment approach.

BACKGROUND: Leiomyosarcoma of visceral organs is uncommon, and pancreatic primary occurrence is even rarer. In terms of curative treatment, patients are generally managed with surgery alone, without significant data on the role or efficacy of adjuvant chemotherapy. CASE PRESENTATION: This manuscript presents a case of a 22-year-old female with advanced primary leiomyosarcoma of the pancreas, treated with radical surgery and adjuvant radiation therapy. CONCLUSION: With a low-survival rate, consideration of radiation therapy in some advanced and unresectable cases could be potentially beneficial.

GPCRdb in 2023: state-specific structure models using AlphaFold2 and new ligand resources.

G protein-coupled receptors (GPCRs) are physiologically abundant signaling hubs routing hundreds of extracellular signal substances and drugs into intracellular pathways. The GPCR database, GPCRdb supports >5000 interdisciplinary researchers every month with reference data, analysis, visualization, experiment design and dissemination. Here, we present our fifth major GPCRdb release setting out with an overview of the many resources for receptor sequences, structures, and ligands. This includes recently published additions of class D generic residue numbers, a comparative structure analysis tool to identify functional determinants, trees clustering GPCR structures by 3D conformation, and mutations stabilizing inactive/active states. We provide new state-specific structure models of all human non-olfactory GPCRs built using AlphaFold2-MultiState. We also provide a new resource of endogenous ligands along with a larger number of surrogate ligands with bioactivity, vendor, and physiochemical descriptor data. The one-stop-shop ligand resources integrate ligands/data from the ChEMBL, Guide to Pharmacology, PDSP Ki and PubChem database. The GPCRdb is available at https://gpcrdb.org.

Outer membrane-anchoring enables LpoB to regulate peptidoglycan synthesis rate.

Peptidoglycan (PG) is an essential component of the cell envelope in most bacteria, responsible for maintaining the shape of the cell and protecting the cell from environmental stresses. The growth of the PG layer during cell elongation and division is facilitated by the coordinated activities of PG synthases and hydrolases. PG synthases are regulated from inside the cell by components of the elongasome and divisome complexes driven by the cytoskeletal proteins MreB and FtsZ. In Escherichia coli the PG synthases PBP1A and PBP1B require the activation by outer membrane (OM)-anchored lipoproteins LpoA and LpoB, respectively. These have an elongated structure and are capable to span the periplasm to reach their cognate, cytoplasmic membrane (CM)-anchored PG synthase through the PG layer. Presumably, the Lpo proteins activate the PBPs at sites where the PG mesh is stretched or defective, resulting in coupling of PG synthase activation with cell growth or PG repair. Here we investigated the importance of OM-anchoring on the function of Lpo proteins in regulating PG synthesis in response to environmental stresses. We investigated the effects of an artificially CM-tethered LpoB on cell morphology and PG synthesis. Our results indicate that mis-localization of LpoB affects the growth and morphology of cells in high osmolarity growth medium, and PG synthesis rate upon an osmotic upshift.

Predictive Value of Endoscopic Observations and Biopsy After Neoadjuvant Chemoradiotherapy in Assessing the Pathologic Complete Response of Patients With Esophageal Squamous Cell Carcinoma.

Introduction: No standard method has been defined to evaluate the therapeutic response of esophageal cancer to neoadjuvant chemoradiotherapy (CRT). This study aimed to determine the predictive value of endoscopic evaluation and biopsy after CRT in predicting the complete pathological response to neoadjuvant CRT in patients with esophageal squamous cell carcinoma (SCC). Materials and Method: This prospective, descriptive study was conducted on patients with stage II and III esophageal SCC who could undergo esophagectomy. Patients underwent neoadjuvant CRT. Four to six weeks after the end of treatment, re-endoscopy was performed and a biopsy was taken in the presence of a tumor lesion. In the absence of a tumor lesion, the marked site of the esophagus was removed as a blind biopsy. Gastrologist observations during endoscopy and the result of the pathological examination of an endoscopic biopsy were recorded. The patient underwent esophagectomy. The pathology obtained from endoscopic biopsy was compared with the pathology response obtained from esophagectomy. Results: Sixty-nine patients were included in the study, of which 32 underwent esophagectomy. In an endoscopic examination after CRT, 28 patients had macroscopic tumor remnants and 4 patients did not. Pathological examination of the samples obtained from endoscopy showed no tumor remnants in 10 patients (31.3%), and in 22 patients (68.7%), living tumor remnants were seen in the biopsy specimen. Pathologic evaluation of the samples obtained by surgical resection showed that in 13 patients, there were no viable carcinomas in the esophagus or lymph nodes removed, and the rate of pathologic complete response was 40.6. Sensitivity, specificity, positive predictive, and negative predictive values of endoscopic observations were 94.7, 23, 64.2, and 75%, respectively. Preoperative biopsy sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 68.4, 30.7, 59, and 40%, respectively. Conclusion: Considering the negative and positive predictive values of endoscopic observations and biopsy after neoadjuvant CRT, it seems that these two methods alone are not suitable for assessing the pathologic complete response after neoadjuvant treatment.

Crystal structures of bacterial small multidrug resistance transporter EmrE in complex with structurally diverse substrates.

Proteins from the bacterial small multidrug resistance (SMR) family are proton-coupled exporters of diverse antiseptics and antimicrobials, including polyaromatic cations and quaternary ammonium compounds. The transport mechanism of the Escherichia coli transporter, EmrE, has been studied extensively, but a lack of high-resolution structural information has impeded a structural description of its molecular mechanism. Here, we apply a novel approach, multipurpose crystallization chaperones, to solve several structures of EmrE, including a 2.9 Å structure at low pH without substrate. We report five additional structures in complex with structurally diverse transported substrates, including quaternary phosphonium, quaternary ammonium, and planar polyaromatic compounds. These structures show that binding site tryptophan and glutamate residues adopt different rotamers to conform to disparate structures without requiring major rearrangements of the backbone structure. Structural and functional comparison to Gdx-Clo, an SMR protein that transports a much narrower spectrum of substrates, suggests that in EmrE, a relatively sparse hydrogen bond network among binding site residues permits increased sidechain flexibility.

Promising Effects of Naringenin and Melatonin against Hepatic Encephalopathy Impairments Induced by Bile Duct Ligation in Male Rats.

BACKGROUND: Bile duct ligation (BDL) is used for evaluating the protective effects of different agents with anti-inflammatory and antioxidant properties against the liver and brain damages. Naringenin (N) and melatonin (M) are used as protectants in various models of diseases. AIMS: In the current research, the combinational effects of these well-known anti-inflammatory and antioxidants agents were investigated against cerebral injuries induced by BDL in male rats. METHODS: The animals were distributed into the following groups: Sham, BDL + Vehicle and BDL+ N + M. Neuronal damages were evaluated using biochemical, motor behavioral tasks and morphological assessments. RESULTS: Based on the data, BDL resulted in decreasing locomotor activity, which was reversed by N and M. Morphological study confirmed that BDL led to neurodegeneration in the cortex of the rats, and the N and M treatment preserved cortical neurons. In addition, immunohistochemical (IHC) study of the rat cortex showed that BDL resulted in increasing the activated astrocytes, and the N and M treatment reduced the number of activated cells. CONCLUSION: These results obviously depicted combinational therapy with N and M to exert positive effects in the BDL rats, probably due to their synergistic anti-inflammatory and antioxidant activities.

Topical henna and curcumin (Alpha®) ointment efficacy for prevention of capecitabine induced hand-foot syndrome: A randomized, triple-blinded, placebo-controlled clinical.

PURPOSE: In this clinical trial, we evaluated Alpha® ointment efficacy in prevention of capecitabine induced hand-foot syndrome (HFS) in patients with gastrointestinal or breast cancers, for the first time. METHODS: During this pilot, randomized, triple-blinded, placebo-controlled clinical trial, the effect of Alpha® ointment (Lawsonia inermis 3 g and Curcuma longa 0.15 g/ 30 g) was assessed. It was applied on the palms and the soles, two times daily starting at the first day of chemotherapy for 4 consecutive courses. The severity of HFS was assessed at the end of the chemotherapy courses based on World Health Organization (WHO) scale and scored between 0-4. RESULTS: Ninety eligible patients were included randomly in the treatment or placebo group. Median WHO HFS grade was not significantly different between the two groups, during the follow-up period (P > 0.05). In the weekly assessment, the scores increased meaningfully in both the placebo and treatment groups, but there was a delay in HFS occurrence and deterioration in Alpha ointment group based on post hoc analysis. CONCLUSION: Administration of Alpha® ointment containing henna and curcumin could not significantly prevent capecitabine induced HFS during 4 courses of treatment, but can somewhat delay its occurrence in patients with gastrointestinal or breast cancer.

Behavioral and Molecular Analysis of Antioxidative Potential of Rosmarinic Acid Against Methamphetamine-induced Augmentation of Casp3a mRNA in the Zebrafish Brain.

INTRODUCTION: Methamphetamine (MA) acts as a powerful oxidant agent, while Rosmarinic Acid (RA) is an effective herbal antioxidant. Oxidative stress-mediated by MA results in apoptosis, and caspase-3 is one of the critical enzymes in the apoptosis process. MA can epigenetically alter gene regulation. In this paper, to investigate the effects of RA on MA-mediated oxidative stress, changes in the level of casp3a mRNA were demonstrated in zebrafish. METHODS: The animals were grouped in 3 treatment conditions for the behavioral test: control, MA, MA pretreated by RA, and 6 treatment conditions for the molecular test: control, RA, MA, MA co-treated with RA, MA co-treated with RA/ZnO/chitosan nanoparticle, and ZnO/chitosan nanoparticle. Then molecular and behavioral investigations were carried out, and critical comparisons were made between the groups.MA solution was prepared with a concentration of 25 mg/L, and RA solution was prepared by DPPH test with the antioxidant power of about 97%. Each solution was administered by immersing 20 zebrafish for 20 minutes, once per day for 7 days. The level of casp3a mRNA was quantified by using qRT-PCR. One-sided trapezoidal tank diving test was applied to study behavioral alterations. RESULTS: The qPCR analysis demonstrated the high potential of RA/ZnO/chitosan in counteracting the MA-mediated elevation in casp3a mRNA level. Based on the diving test results of MA-treated fish, MA was found to be anxiolytic compared to the control. While the resulted diving pattern of the MA-treated animals pretreated by RA was novel and different from both the control and MA-treated groups. CONCLUSION: The potential of RA combined with a suitable nanoparticle against MA-induced oxidative stress was supported. The high efficiency of ZnO/chitosan in increasing RA penetration to the brain cells was evident. MA at a dose of 25 mg/L is anxiolytic for zebrafish. However, the molecular mechanisms involved in these processes should be studied.

Effects of a polyherbal formulation on the quality of life and survival of patients with common upper gastrointestinal cancers: A randomized placebo-controlled trial.

OBJECTIVE: Previous clinical trials have suggested that herbal medicines can improve the quality of life (QOL) and survival of cancer patients. This study was aimed to evaluate the effects of a polyherbal compound (PHC, formulated as syrup) consisting of Allium sativum, Curcuma longa, Panax ginseng, and Camellia sinensis on the quality of life (QOL) and survival in patients with upper gastrointestinal cancers. MATERIALS AND METHODS: A randomized placebo-controlled trial was carried out on patients with esophageal or gastric cancer who had finished their oncological treatments. The patients were randomly assigned to PHC (n=20) or placebo (n=20) group. The PHC group was treated with the PHC for 12 weeks, while the placebo group received 70% sucrose syrup. The QOL was assessed at baseline and after 12 weeks. The patients were followed for up to 24 months to determine overall survival. RESULTS: PHC significantly improved cancer-related symptoms, physical performance, and psychological and social functions of the patients (p<0.05 for all cases). Death occurred in 33 and 22% of cases in the placebo and PHC group, respectively. The mean survival time was 16.8 months (95% CI: 12.8-20.9) in the placebo group and 21.4 months (95% CI: 19.1-23.6) in the PHC group but the difference was not statistically significant. CONCLUSION: The PHC improved cancer-related symptoms, physical performance, and psychological and social functions in patients with gastrointestinal cancers. It seems that this herbal compound has the potential to be used as a supplement in the management of cancer.

Improving sustainability and mitigating environmental impacts of agro-biowaste compost fertilizer by pelletizing-drying.

The use of agro-biowaste compost fertilizers in agriculture is beneficial from technical, financial, and environmental perspectives. Nevertheless, the physical, mechanical, and agronomical attributes of agro-biowaste compost fertilizers should be engineered to reduce their storage, handling, and utilization costs and environmental impacts. Pelletizing and drying are promising techniques to achieve these goals. In the present work, the effects of process parameters, including compost particle size/moisture content, pelletizing compression ratio, and drying air temperature/velocity, were investigated on the density, specific crushing energy, and moisture diffusion of agro-biowaste compost pellet. The Taguchi technique was applied to understand the effects of independent parameters on the output responses, while the optimal pellet properties were found using the iterative thresholding method. The soil and plant (sweet basil) response to the optimal biocompost pellet was experimentally evaluated. The farm application of the optimal pellet was also compared with the untreated agro-biowaste compost using the life cycle assessment approach to investigate the potential environmental impact mitigation of the pelletizing and drying processes. Generally, the compost moisture content was the most influential factor on the density and specific crushing energy of the dried pellet, while the moisture diffusion of the wet pellet during the drying process was significantly influenced by the pelletizing compression ratio. The density, specific crushing energy, and moisture diffusion of agro-biowaste compost pellet at the optimal conditions were 1242.49 kg/m3, 0.5054 MJ/t, and 8.2 × 10-8 m2/s, respectively. The optimal biocompost pellet could release 80% of its nitrogen content evenly over 98 days, while this value was 28 days for the chemical urea fertilizer. Besides, the optimal pellet could significantly improve the agronomical attributes of the sweet basil plant compared with the untreated biocompost. The applied strategy could collectively mitigate the weighted environmental impact of farm application of the agro-biowaste compost by more than 63%. This reduction could be attributed to the fact that the pelletizing-drying processes could avoid methane emissions from the untreated agro-biowaste compost during the farm application. Overall, pelletizing-drying of the agro-biowaste compost could be regarded as a promising strategy to improve the environmental and agronomical performance of farm application of organic biofertilizers.

Improved healing of critical-size femoral defect in osteoporosis rat models using 3D elastin/polycaprolactone/nHA scaffold in combination with mesenchymal stem cells.

Osteoporosis is a common bone disease that results in elevated risk of fracture, and delayed bone healing and impaired bone regeneration are implicated by this disease. In this study, Elastin/Polycaprolactone/nHA nanofibrous scaffold in combination with mesenchymal stem cells were used to regenerate bone defects. Cytotoxicity, cytocompatibility and cellular morphology were evaluated in vitro and observations revealed that an appropriate environment for cellular attachment, growth, migration, and proliferation is provided by this scaffold. At 3 months following ovariectomy (OVX), the rats were used as animal models with an induced critical size defect in the femur to evaluate the therapeutic potential of osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) seeded on 3 dimension (3D) scaffolds. In this experimental study, 24 female Wistar rats were equally divided into three groups: Control, scaffold (non-seeded BM-MSC), and scaffold + cell (seeded BM-MSC) groups. 30 days after surgery, the right femur was removed, and underwent a stereological analysis and RNA extraction in order to examine the expression of Bmp-2 and Vegf genes. The results showed a significant increase in stereological parameters and expression of Bmp-2 and Vegf in scaffold and scaffold + cell groups compared to the control rats. The present study suggests that the use of the 3D Elastin/Polycaprolactone (PCL)/Nano hydroxyapatite (nHA) scaffold in combination with MSCs may improve the fracture regeneration and accelerates bone healing at the osteotomy site in rats.