An overview of pharmacological effects of Crocus sativous and its constituents.

Crocus sativus L. was used for the treatment of a wide range of disorders in traditional medicine. Due to the extensive protective and treatment properties of C. sativus and its constituents in various diseases, the purpose of this review is to collect a summary of its effects, on experimental studies, both in vitro and in vivo. Databases such as PubMed, Science Direct, and Scopus were explored until January 2023 by employing suitable keywords. Several investigations have indicated that the therapeutic properties of C. sativus may be due to its anti-oxidant and anti-inflammatory effects on the nervous, cardiovascular, immune, and respiratory systems. Further research has shown that its petals also have anticonvulsant properties. Pharmacological studies have shown that crocetin and safranal have anti-oxidant properties and through inhibiting the release of free radicals lead to the prevention of disorders such as tumor cell proliferation, atherosclerosis, hepatotoxicity, bladder toxicity, and ethanol induced hippocampal disorders. Numerous studies have been performed on the effect of C. sativus and its constituents in laboratory animal models under in vitro and in vivo conditions on various disorders. This is necessary but not enough and more clinical trials are needed to investigate unknown aspects of the therapeutic properties of C. sativus and its main constituents in different disorders.

Feasibility Study of Convolutional Long ShortTerm Memory Network for Pulmonary Movement Prediction in CT Images.

Background: During X-ray imaging, pulmonary movements can cause many image artifacts. To tackle this issue, several studies, including mathematical algorithms and 2D-3D image registration methods, have been presented. Recently, the application of deep artificial neural networks has been considered for image generation and prediction. Objective: In this study, a convolutional long short-term memory (ConvLSTM) neural network is used to predict spatiotemporal 4DCT images. Material and Methods: In this analytical analysis study, two ConvLSTM structures, consisting of stacked ConvLSTM models along with the hyperparameter optimizer algorithm and a new design of the ConvLSTM model are proposed. The hyperparameter optimizer algorithm in the conventional ConvLSTM includes the number of layers, number of filters, kernel size, epoch number, optimizer, and learning rate. The two ConvLSTM structures were also evaluated through six experiments based on Root Mean Square Error (RMSE) and structural similarity index (SSIM). Results: Comparing the two networks demonstrates that the new design of the ConvLSTM network is faster, more accurate, and more reliable in comparison to the tuned-stacked ConvLSTM model. For all patients, the estimated RMSE and SSIM were 3.17 and 0.988, respectively, and a significant improvement can be observed in comparison to the previous studies. Conclusion: Overall, the results of the new design of the ConvLSTM network show excellent performances in terms of RMSE and SSIM. Also, the generated CT images with the new design of the ConvLSTM model show a good consistency with the corresponding references regarding registration accuracy and robustness.

Current status of nano-vaccinology in veterinary medicine science.

Vaccination programmes provide a safe, effective and cost-efficient strategy for maintaining population health. In veterinary medicine, vaccination not only reduces disease within animal populations but also serves to enhance public health by targeting zoonoses. Nevertheless, for many pathogens, an effective vaccine remains elusive. Recently, nanovaccines have proved to be successful for various infectious and non-infectious diseases of animals. These novel technologies, such as virus-like particles, self-assembling proteins, polymeric nanoparticles, liposomes and virosomes, offer great potential for solving many of the vaccine production challenges. Their benefits include low immunotoxicity, antigen stability, enhanced immunogenicity, flexibility sustained release and the ability to evoke both humoral and cellular immune responses. Nanovaccines are more efficient than traditional vaccines due to ease of control and plasticity in their physio-chemical properties. They use a highly targeted immunological approach which can provide strong and long-lasting immunity. This article reviews the currently available nanovaccine technology and considers its utility for both infectious diseases and non-infectious diseases such as auto-immunity and cancer. Future research opportunities and application challenges from bench to clinical usage are also discussed.

MiR-548 K regulatory effect on the ABCG2 gene expression in MDR breast cancer cells.

BACKGROUND: multidrug resistance (MDR) is One of the foremost challenges in overcoming breast cancer. Various molecular processes are involved in the development of MDR in breast cancer cells, including over expression of ABC transporters such as ABCG2 (BCRP), increase breast cancer stem cells drug resistance, and epithelial mesenchymal transition. AIMS: In the present study, we used bioinformatics and experimental analysis to investigate the role of miR-548 K, in the modulating of ABCG2, in MDR breast cancer cells. METHODS AND RESULTS: In silico inspections introduce 14 microRNAs targeting 3'-UTR region of ABCG2 transcripts, which are probably involved in breast cancer drug resistance. An association was highlighted between miR-548 k with ABC transporter family. The expression level of ABCG2 gene in MCF7-MX cell lines was significantly more than MCF7 cell lines. On the other hand, we increased the expression of miR-548 K in MCF7-MX and MCF7 cell lines through its transfection, which dramatically coincided with decreasion in the ABCG2 transcripts level. Additional studies on patient samples revealed that the expression of ABCG2 showed an increase in ABCG2 level in neoadjuvant chemotherapy drugs resistance (NCDR) patients compared to primary pre-operative chemotherapy drugs response (PCDR) patients. Also, a reduction in the expression of miR-548 K in NCDR patients was revealed. CONCLUSION: The results of our study suggest that miR-548 K may be involved in modulating the expression of ABCG2 in MDR breast cancer cells.

Non-coding RNAs and epithelial mesenchymal transition in cancer: molecular mechanisms and clinical implications.

Epithelial-mesenchymal transition (EMT) is a fundamental process for embryonic development during which epithelial cells acquire mesenchymal characteristics, and the underlying mechanisms confer malignant features to carcinoma cells such as dissemination throughout the organism and resistance to anticancer treatments. During the past decades, an entire class of molecules, called non-coding RNA (ncRNA), has been characterized as a key regulator of almost every cellular process, including EMT. Like protein-coding genes, ncRNAs can be deregulated in cancer, acting as oncogenes or tumor suppressors. The various forms of ncRNAs, including microRNAs, PIWI-interacting RNAs, small nucleolar RNAs, transfer RNA-derived RNA fragments, long non-coding RNAs, and circular RNAs can orchestrate the complex regulatory networks of EMT at multiple levels. Understanding the molecular mechanism underlying ncRNAs in EMT can provide fundamental insights into cancer metastasis and may lead to novel therapeutic approaches. In this review, we describe recent advances in the understanding of ncRNAs in EMT and provide an overview of recent ncRNA applications in the clinic.

ESRG, LINC00518 and PWRN1 are newly-identified deregulated lncRNAs in colorectal cancer.

Colorectal cancer is the 2nd leading cause of death in humans because of cancer. This rank of death could be due to the high rate of incidence from one hand, and the lack of sufficient diagnostic and therapeutic approaches from the other hand. Thus, molecular tools have been emerging as the potential biomarker to improve the early diagnosis and therapeutic management that subsequently could lead to the heightened survival rate of colorectal cancer patients. Long non-coding RNA (lncRNAs) have shown promising capabilities to be used in clinics. The profiling methods could identify novel aberrantly expressed lncRNAs in colorectal cancer. We, thus, performed a comprehensive and unbiased approach to shortlist the dysregulated lncRNAs based on the colon adenocarcinoma TCGA data. An unbiased in silico method was used to rank the yet to profiled lncRNAs in colorectal cancer. qPCR was used to measure the expression level of selected lncRNAs. Our results nominated ESRG, LINC00518, PWRN1, and TTTY14 lncRNAs as the top-hit novel lncRNAs with aberrant expression in colon cancer. The qPCR method was used to profile these lncRNAs that showed the up-regulation of ESRG and LINC00518, and down-regulation of TTTY14 in thirty paired colorectal cancer specimens. The statistical analyses demonstrated that ESRG, LINC00518 and PWRN1 could distinguish the tumor from normal samples. Moreover, ESRG showed a negative correlation with the overall survival of patients. These diagnostic and prognostic results suggest that profiling ESRG, LINC00518 and PWRN1 s may have implications in clinics.

The role of FOXP3 rs3761548 and rs2294021 polymorphisms in pediatrics acute lymphoblastic leukemia: association with risk and response to therapy.

FOXP3 X-linked gene has crucial roles in the development and function of regulatory T cells. We investigated the association of FOXP3 rs3761548, rs3761549 and rs2294021 single nucleotide polymorphisms (SNPs) with acute lymphoblastic leukemia (ALL) susceptibility and response to therapy. Genotyping was performed in 247 patients and 210 healthy subjects. We observed a higher frequency of rs3761548 A carriers and rs2294021 C carriers (p < 0.04) in male patients, and lower frequencies of rs3761548 AC genotype (p = 0.04) and rs2294021 CT genotype (p = 0.01) in female patients compared to controls. ACC (p = 0.04) and ATC haplotypes (p = 0.002) were associated with susceptibility to ALL. There was a significant correlation between the genotypes of rs3761548 and rs2294021 SNPs with event-free survival (EFS) and overall survival (OS). The rs3761548 A genotype in male patients was associated with increased risk of relapse (p < 0.0001), shorter EFS, increased death rate (p = 0.002) and shorter OS compared to C genotype (p = 0.001). Similar significant results were observed for the relation of rs2294021 C genotype with response to therapy in male patients. In females, patients with rs3761548 AC genotype had longer EFS (p = 0.02) and those with rs2294021 CT had longer EFS and OS (p < 0.005). According to haplotype analysis, patients carrying ACC or ATC haplotypes had the highest number of WBCs and shorter EFS or OS, and patients with CCT haplotype had the lowest number of WBCs and longer EFS or OS. These results provided evidence for the impact of these polymorphisms on susceptibility and response to therapy in children with ALL.

Anti-inflammatory, anti-oxidant, and immunomodulatory activities of the genus Ferula and their constituents: A review.

Ferula is a genus of the family Apiaceae and it includes around 170 species of flowering plants mostly native to the Mediterranean region and eastern to central Asia. In Iran, Ferula spp. are widely used in cuisine and traditional medicine. This review discusses the anti-inflammatory, anti-oxidant, and immunomodulatory activities of different species of Ferula. To prepare the present review, Scopus, Google Scholar, PubMed, and Web of Science scientific databases were searched to retrieve relevant articles published from 1985 until December 2020. Based on our literature review, Ferula plants and their derivatives decrease the levels of inflammatory mediators and exert anti-apoptotic effects. Under oxidative stress conditions, these plants and their constituents were shown to decrease oxidative markers such as malondialdehyde, reactive oxygen species, and nitric oxide but increase superoxide dismutase, glutathione peroxidase, catalase activity, and glutathione level. Ferula plants and their constituents also showed immunomodulatory effects by affecting various cytokines. Besides, in vivo and in vitro studies showed hypotensive, neuroprotective, memory-enhancing, anti-oxidant, hepatoprotective, antimicrobial, anticarcinogenic, anticytotoxic, antiobesity, and anthelmintic effects for various species of Ferula and their constituents. These plants also showed a healing effect on gynecological issues such as miscarriage, unusual pain, difficult menstruation, and leukorrhea. All these beneficial effects could have resulted from the anti-inflammatory, anti-oxidant, and immunomodulatory effects of these plants and their constituents. Based on the available literature, members of the genus Ferula can be regarded as potential therapeutics against inflammatory conditions, oxidative stress, and immune dysregulation.

Fractionated radiation promotes proliferation and radioresistance in bystander A549 cells but not in bystander HT29 cells.

AIMS: Recent studies suggest that direct exposure of cells to fractionated radiotherapy might induce radioresistance. However, the effects of fractionated radiotherapy on the non-irradiated bystander cells remain unclear. We hypothesized that fractionated radiotherapy could enhance radioresistance and proliferation of bystander cells. MAIN METHODS: Human tumor cell lines, including A549 and HT29 were irradiated (2 Gy per day). The irradiated cells (either A549 or HT29) were co-cultured with non-irradiated cells of the same line using transwell co-culture system. Tumor cell proliferation, radioresistance and apoptosis were measured using MTT assay, clonogenic survival assay and Annexin-V in bystander cells, respectively. In addition, activation of Chk1 (Ser 317), Chk2 (Thr 68) and Akt (Ser473) were measured via western blot. KEY FINDINGS: Irradiated HT29 cells induced conventional bystander effects detected as modulation of clonogenic survival parameters (decreased area under curve, D10 and ED50 and increased α) and proliferation in recipient neighbors. While, irradiated A549 cells significantly enhanced the radioresistance and proliferation of bystander cells. These changes were accompanied with enhanced activation of Chk1, Chk2 and Akt in non-irradiated bystander A549 cells. Moreover, both bystander effects (damaging and protective) were mediated through secreted factors. SIGNIFICANCE: These findings suggest that fractionated radiotherapy could promote proliferation and radioresistance of bystander cells probably through survival and proliferation pathways.

IL-35 and IL-18 Serum Levels in Children With Acute Lymphoblastic Leukemia: The Relationship With Prognostic Factors.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer among children. In this study, we investigated the serum levels of interleukin (IL)-35 and IL-18 in children with ALL to compare with healthy subjects and find their relationship with prognostic factors and response to therapy. IL-35 and IL-18 serum concentrations in 40 children diagnosed with ALL and 35 age-matched and sex-matched healthy children were measured using ELISA. The association between cytokine levels and patients' clinical and laboratory data were determined. A significant difference was found in IL-35 serum levels between the patients (3.6±1.5 ng/mL) and controls (2.5±1.8 ng/mL) (P=0.007). No significant difference in IL-18 serum levels between these groups was observed. A positive correlation between IL-35 and IL-18 levels was detected (P=0.001). The authors found that patients with lower platelet count had higher IL-35 concentration (P=0.003). By considering a cut-off value of 6.21 ng/mL (mean±2SD of controls) for IL-35, it was found that white blood cell (WBC) count was higher in patients with IL-35 >6.21 ng/mL (P=0.016), and the majority of these patients had T-ALL (P=0.01). Although the mean overall survival in patients with IL-35 >6.21 ng/mL was shorter (937±381 d) than in those with IL-35 ≤6.21 ng/mL (1567±103 d), but the result was not significant (P=0.1, log-rank test). The IL-18 level was associated with a lower hemoglobin level (P=0.027). These data suggested a role for IL-35 in ALL development. The significant relation of IL-35 to white blood cells and platelet counts may imply a possible influence of IL-35 on ALL prognosis.

Synthesis, characterization and photocatalytic application of Ag-doped Fe-ZSM-5@TiO2 nanocomposite for degradation of reactive red 195 (RR 195) in aqueous environment under sunlight irradiation.

BACKGROUND: Most dyes have aromatic rings in their structures, which make them highly toxic for human being and aquatic life. Heterogeneous photodegradation using TiO2 nanoparticles is one of the most applied methods used for dye removal. The wide band gap of TiO2 nanoparticles disables its use of the visible light and thus the vast potential of sunlight. To overcome this deficiency, Ag doped TiO2 nanoparticles were loaded on Fe-ZSM-5. METHODS: Fe-ZSM-5@TiO2-Ag photocatalyst was synthesized through sol-gel and hydrothermal methods to remove hazardous Reactive Red 195 (RR 195) from aqueous solution. RESULTS: Pure phase of Fe-ZSM-5@TiO2-Ag with specific surface area of 332 m2/g was successfully synthesized. Formation of Ti-O-Ag functional group in the photocatalyst structure confirmed the nanocomposite form of the product. SEM and TEM images portrayed the synthesized zeolite and photocatalyst NPs in a size range of ≤100 nm with homogenous distribution of Ag doped TiO2 on Fe-ZSM-5 surface. The band-gap energy of Fe-ZSM-5@TiO2-Ag was calculated 1.97 eV at λ = 630 nm. Photocatalytic activity of the photocatalyst under natural sunlight was investigated through photodecomposition of RR 195 in an aqueous solution. The dye photodecomposition of about 98% was achieved at photocatalyst concentration of 400 mg/L, pH of 3, and dye concentration of 50 mg/L at ambient temperature after 120 min under sunlight using 0.5 ml of TiO2 and silver ammonium nitrate. The photocatalyst reusability was found significant after 5 frequent cycles. CONCLUSION: The novel Ag-doped TiO2-Fe-ZSM-5 nanocomposite with sunlight sensitivity can be a promising candidate to purify wastewater containing organic pollutants.

The contribution of beta-2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels and cyclooxygenase pathway in the relaxant effect of Allium cepa L. on the tracheal smooth muscle.

ETHNOPHARMACOLOGICAL RELEVANCE: There are report regarding therapeutic effects for Allium cepa L. (A. cepa) in Iranian traditional medicine and the plant has showed anti-inflammatory, anti-allergic, anti-hyperglycemic, antioxidant, anti-cancer, anti-hypertension, anti-hypercholesterolemia and anti-asthmatic activities in previous studies. AIM OF THE STUDY: In this study, the contribution of ß2 adrenergic, muscarinic and histamine (H1) receptors, calcium and potassium channels, and cyclooxygenase pathway in the relaxant effect of A. cepa extract on tracheal smooth muscle (TSM) was assessed. MATERIALS AND METHODS: TSM was contracted by KCl (60 mM) or methacholine (10 µM) for 5 min and cumulative concentrations of A. cepa extract (2, 4, 8, 16, 32 and 64 mg/ml) were added to organ bath every 5 min. Theophylline (0.2, 0.4, 0.6 and 0.8 mM) as positive control, and saline (1 ml) as negative control were also examined in non-incubated tissues. The relaxant effect of A. cepa extract was examined on non-incubated and incubated TSM with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide and indomethacin. RESULTS: A. cepa showed concentration-dependent relaxant effects on non-incubated TSM contracted by KCl (60 mM) or methacholine (10 µM), (P < 0.01 to p < 0.001). There was no significant difference in the relaxant effects of A. cepa between non-incubated and incubated tissues with glibenclamide, atropine, chlorpheniramine and indomethacin. The plant extract showed significant lower relaxant effects in incubated TSM with propranolol and diltiazem compared to non-incubated tissues. EC50 values of A. cepa extract in incubated TSM with propranolol and diltiazem were significantly lower than non-incubated tissues (p < 0.001 and p < 0.05, respectively). The relaxant effects of different concentrations of the extract of A. cepa were not significantly different with those of theophylline. The concentrations of A. cepa extract and theophylline were significant correlated with their relaxant effects (p < 0.05 to p < 0.001). In incubated TSM with propranolol and diltiazem, concentration ratio minus one (CR-1) values was positive (2.65 ±â€¯0.63 and 1.28 ±â€¯0.43 respectively). CONCLUSION: The A. cepa extract showed relatively potent relaxant effect on TSM which was comparable to the effect of theophylline. The results showed that ß2-adrenergic stimulatory and/or calcium channel blockade are the possible mechanisms for the relaxant effects of the plant.

Molecular design and synthesis of new dithiocarbazate complexes; crystal structure, bioactivities and nano studies.

The syntheses of a new set of metal complexes MoO2L'(CH3OH), VOL'(CH3O)(CH3OH), , , SnL'Cl2 and SnL'I2 with a new ligand (L = (2,2'(disulfanediylbis((ethylthio)methylene)bis(hydrazin-2-yl-1-ylidene)bis(methanylylidene)) diphenol; L' = S-ethyl-3-(2-hydroxyphenyl)methylenedithiocarbazate are described along with characterization by elemental analysis, mass spectrometry, spectroscopic (IR, 1H- and 13C-NMR) and TGA techniques. The crystal structures of compounds were determined by single crystal X-ray diffraction analysis and compared to powder X-ray diffraction (PXRD) patterns of the nano complexes obtained using ultrasonic methods. The PXRD results indicate that the compounds synthesized by ultrasonic methods have high crystallinity. The compounds were evaluated in an in vitro cytotoxicity study with two human cancer cell lines. The results of this study revealed that all complexes exhibit good cytotoxic activity when compared to the clinical drug, cisplatin. Interaction of the samples with human serum albumin (HSA) was investigated using fluorescence spectrophotometric methods and the Stern-Volmer quenching constant (K SV) and free energy changes (ΔG) were calculated at 298 K. The fluorescence quenching method is used to determine the number of binding sites (n) and association constants (K a) at the same temperatures.

S-allyl cysteine ameliorates cognitive deficits in streptozotocin-diabetic rats via suppression of oxidative stress, inflammation, and acetylcholinesterase.

Diabetes mellitus (DM) is associated with learning, memory, and cognitive deficits. S-allyl cysteine (SAC) is the main organosulfur bioactive molecule in aged garlic extract with anti-diabetic, antioxidant, anti-inflammatory and nootropic property. This research was conducted to evaluate the efficacy of SAC on alleviation of learning and memory deficits in streptozotocin (STZ)-diabetic rats and to explore involvement of toll-like receptor 4 (TLR4), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor-kappa B (NF-κB), and heme oxygenase 1 (HO-1) signaling cascade. Male Wistar rats were divided into control, diabetic, SAC-treated diabetic, and glibenclamide-treated diabetic (positive control) groups. SAC was administered at a dose of 150mg/kg for seven weeks. Treatment of diabetic rats with SAC lowered serum glucose, improved spatial recognition memory in Y maze, discrimination ratio in novel object recognition task, and restored step-through latency (STL) in passive avoidance paradigm. In addition, SAC reduced acetylcholinesterase activity, lipid peroxidation marker malondialdehyde (MDA) and augmented antioxidant defensive system including superoxide dismutase (SOD), catalase and reduced glutathione (GSH) in hippocampal lysate. Meanwhile, SAC lowered hippocampal NF-kB, TLR4, and TNFα and prevented reduction of Nrf2 and heme oxygenase-1 (HO-1) in diabetic rats. Taken together, chronic SAC treatment could ameliorate cognitive deficits in STZ-diabetic rats through modulation of Nrf2/NF-κB/TLR4/HO-1, and acetylcholinesterase and attenuation of associated oxidative stress and neuroinflammation.

Aptamer decorated hyaluronan/chitosan nanoparticles for targeted delivery of 5-fluorouracil to MUC1 overexpressing adenocarcinomas.

An aptamer (Apt) conjugated hyaluronan/chitosan nanoparticles (HACSNPs) were prepared as carrier for targeted delivery of 5-fluorouracil (5FU) to mucin1 (MUC1) overexpressing colorectal adenocarcinomas. Nanoparticles had about 181 nm size, encapsulation efficiency of 45.5 ± 2.8 and acceptable stability. Conjugation of MUC1-binding Apt to the surface of the nanoparticles was confirmed by gel electrophoresis. Toxicity and cellular uptake of nanoparticles were investigated by in vitro cytotoxicity assays and confocal scanning microscopy in (MUC1(+)) human adenocarcinoma and (MUC1(-)) Chinese hamster ovary cells. Toxicity of nanoparticles were significantly higher in comparison with free drug in both cell lines while this rising was more efficient for nanoparticles decorated with Apt in MUC1(+) cell line. The same result was observed in the cellular uptake study. It could be concluded that the present system has the potential to be considered in treatment of MUC1(+) colorectal adenocarcinomas.