Unraveling the function and structure impact of deleterious missense SNPs in the human OX1R receptor by computational analysis.

The orexin/hypocretin receptor type 1 (OX1R) plays a crucial role in regulating various physiological functions, especially feeding behavior, addiction, and reward. Genetic variations in the OX1R have been associated with several neurological disorders. In this study, we utilized a combination of sequence and structure-based computational tools to identify the most deleterious missense single nucleotide polymorphisms (SNPs) in the OX1R gene. Our findings revealed four highly conserved and structurally destabilizing missense SNPs, namely R144C, I148N, S172W, and A297D, located in the GTP-binding domain. Molecular dynamics simulations analysis demonstrated that all four most detrimental mutant proteins altered the overall structural flexibility and dynamics of OX1R protein, resulting in significant changes in the structural organization and motion of the protein. These findings provide valuable insights into the impact of missense SNPs on OX1R function loss and their potential contribution to the development of neurological disorders, thereby guiding future research in this field.

An actor-model framework for visual sensory encoding.

A fundamental challenge in neuroengineering is determining a proper artificial input to a sensory system that yields the desired perception. In neuroprosthetics, this process is known as artificial sensory encoding, and it holds a crucial role in prosthetic devices restoring sensory perception in individuals with disabilities. For example, in visual prostheses, one key aspect of artificial image encoding is to downsample images captured by a camera to a size matching the number of inputs and resolution of the prosthesis. Here, we show that downsampling an image using the inherent computation of the retinal network yields better performance compared to learning-free downsampling methods. We have validated a learning-based approach (actor-model framework) that exploits the signal transformation from photoreceptors to retinal ganglion cells measured in explanted mouse retinas. The actor-model framework generates downsampled images eliciting a neuronal response in-silico and ex-vivo with higher neuronal reliability than the one produced by a learning-free approach. During the learning process, the actor network learns to optimize contrast and the kernel's weights. This methodological approach might guide future artificial image encoding strategies for visual prostheses. Ultimately, this framework could be applicable for encoding strategies in other sensory prostheses such as cochlear or limb.

Backpropagation-free training of deep physical neural networks.

Recent successes in deep learning for vision and natural language processing are attributed to larger models but come with energy consumption and scalability issues. Current training of digital deep-learning models primarily relies on backpropagation that is unsuitable for physical implementation. In this work, we propose a simple deep neural network architecture augmented by a physical local learning (PhyLL) algorithm, which enables supervised and unsupervised training of deep physical neural networks without detailed knowledge of the nonlinear physical layer's properties. We trained diverse wave-based physical neural networks in vowel and image classification experiments, showcasing the universality of our approach. Our method shows advantages over other hardware-aware training schemes by improving training speed, enhancing robustness, and reducing power consumption by eliminating the need for system modeling and thus decreasing digital computation.

Computational analysis of the functional and structural impact of the most deleterious missense mutations in the human Protein C.

Protein C (PC) is a vitamin K-dependent factor that plays a crucial role in controlling anticoagulant processes and acts as a cytoprotective agent to promote cell survival. Several mutations in human PC are associated with decreased protein production or altered protein structure, resulting in PC deficiency. In this study, we conducted a comprehensive analysis of nonsynonymous single nucleotide polymorphisms in human PC to prioritize and confirm the most high-risk mutations predicted to cause disease. Of the 340 missense mutations obtained from the NCBI database, only 26 were classified as high-risk mutations using various bioinformatic tools. Among these, we identified that 12 mutations reduced the stability of protein, and thereby had the greatest potential to disturb protein structure and function. Molecular dynamics simulations revealed moderate alterations in the structural stability, flexibility, and secondary structural organization of the serine protease domain of human PC for five missense mutations (L305R, W342C, G403R, V420E, and W444C) when compared to the native structure that could maybe influence its interaction with other molecules. Protein-protein interaction analyses demonstrated that the occurrence of these five mutations can affect the regular interaction between PC and activated factor V. Therefore, our findings assume that these mutants can be used in the identification and development of therapeutics for diseases associated with PC dysfunction, although assessment the effect of these mutations need to be proofed in in-vitro.

Computational analysis of missense variant CYP4F2*3 (V433M) in association with human CYP4F2 dysfunction: a functional and structural impact.

BACKGROUND: Cytochrome P450 4F2 (CYP4F2) enzyme is a member of the CYP4 family responsible for the metabolism of fatty acids, therapeutic drugs, and signaling molecules such as arachidonic acid, tocopherols, and vitamin K. Several reports have demonstrated that the missense variant CYP4F2*3 (V433M) causes decreased activity of CYP4F2 and inter-individual variations in warfarin dose in different ethnic groups. However, the molecular pathogenicity mechanism of missense V433M in CYP4F2 at the atomic level has not yet been completely elucidated. METHODS AND RESULTS: In the current study, we evaluated the effect of the V433M substitution on CYP4F2 using 14 different bioinformatics tools. Further molecular dynamics (MD) simulations were performed to assess the impact of the V433M mutation on the CYP4F2 protein structure, stability, and dynamics. In addition, molecular docking was used to illustrate the effect of V433M on its interaction with vitamin K1. Based on our results, the CYP4F2*3 variant was a damaging amino acid substitution with a destabilizing nature. The simulation results showed that missense V433M affects the dynamics and stability of CYP4F2 by reducing its compactness and stability, which means that it tends to change the overall structural conformation and flexibility of CYP4F2. The docking results showed that the CYP4F2*3 variant decreased the binding affinity between vitamin K1 and CYP4F2, which reduced the activity of CYP4F2*3 compared to native CYP4F2. CONCLUSIONS: This study determined the molecular pathogenicity mechanism of the CYP4F2*3 variant on the human CYP4F2 protein and provided new information for understanding the structure-function relationship of CYP4F2 and other CYP4 enzymes. These findings will aid in the development of effective drugs and treatment options.

Evaluation of a warfarin dosing algorithm including CYP2C9, VKORC1, and CYP4F2 polymorphisms and non-genetic determinants for the Iranian population.

BACKGROUND: The response to warfarin, as an oral anticoagulant agent, varies widely among patients from different ethnic groups. In this study, we tried to ascertain and determine the relationship between non-genetic factors and genetic polymorphisms with warfarin therapy; we then proposed a new warfarin dosing prediction algorithm for the estimation of drug sensitivity and resistance in the Iranian population. METHODS: Overall, 200 warfarin-treated patients with stable doses were recruited, the demographic and clinical characteristics were documented, and genotyping was done using a sequencing assay. RESULTS: The outcomes of our investigation showed that the genetic polymorphisms of VKORC1(-1639 G > A), CYP2C9*3, CYP2C9*2, amiodarone use, and increasing age were found to be related to a significantly lower mean daily warfarin dose. In contrast, the CYP4F2*3 variant and increased body surface area were linked with an increased dose of warfarin in the Iranians. Our descriptive model could describe 56.5% of the variability in response to warfarin. This population-specific dosing model performed slightly better than other previously published warfarin algorithms for our patient's series. Furthermore, our findings provided the suggestion that incorporating the CYP4F2*3 variant into the dosing algorithm could result in a more precise calculation of warfarin dose requirements in the Iranian population. CONCLUSIONS: We proposed and validated a population-specific dosing algorithm based on genetic and non-genetic determinants for Iranian patients and evaluated its performance. Accordingly, by using this newly developed algorithm, prescribers could make more informed decisions regarding the treatment of Iranian patients with warfarin.

KRAS, NRAS, BRAF, and PIK3CA mutation rates, clinicopathological association, and their prognostic value in Iranian colorectal cancer patients.

AIM: Mutations in KRAS, NRAS, BRAF, and PIK3CA genes are critical factors in clinical evaluation of colorectal cancer (CRC) development and progression. In Iran, however, the data regarding genetic profile of CRC patients is limited except for KRAS exon2 and BRAF V600F mutations. This study aimed to investigate the mutational spectrum and prognostic effects of these genes and explore the relationship between these mutations and clinicopathological features of CRC. METHOD: To achieve these objectives, mutations in KRAS (exons 2, 3, and 4), NRAS (exons 2, 3, and 4), PIK3CA (exons 9 and 20), and BRAF (exon 15) was determined using PCR and pyrosequencing in a total of 151 patients with colorectal cancer. RESULTS: KRAS, BRAF, NRAS, and PIK3CA mutations were identified in 41%, 5.96%, 3.97%, and 13.24% of the cases, respectively. There were some significant correlations between clinicopathological features and KRAS, PIK3CA, BRAF, and NRAS mutations. Mutations in KRAS and PIK3CA were shown to be independent risk factors for poor survival of the patients at stage I-IV (p < 0.0001 and p = 0.001, respectively). No significant impact on prognosis was observed in patients with BRAF mutations. CONCLUSION: Our study revealed the prevalence of CRC biomarkers mutations in Iranian patients and emphasized the role of KRAS and PIK3CA on shorter overall survival rates in this population.

The interaction mechanism of candidone with calf thymus DNA: A multi-spectroscopic and MD simulation study.

In this investigation, the effects of candidone on the structure and conformation of DNA were evaluated by spectroscopic methods, molecular dynamics simulation, and molecular docking studies. Fluorescence emission peaks, ultraviolet-visible spectra, and molecular docking exhibited the complex formation between candidone and DNA in a groove-binding mode. Fluorescence spectroscopy results also showed a static quenching mechanism of DNA in the presence of candidone. Moreover, thermodynamic parameters demonstrated that candidone spontaneously bound to DNA with a high binding affinity. The hydrophobic interactions were the dominant forces over the binding process. Based on the Fourier transform infrared data candidone tended to attach to the A-T base pairs of the minor grooves of DNA. The thermal denaturation and circular dichroism measurements displayed that candidone caused a slight change in the DNA structure, which was confirmed by the molecular dynamics simulation results. According to the obtained findings from the molecular dynamic simulation, the structural flexibility and dynamics of DNA were altered to a more extended structure.

Clinicopathological Significance of PTEN Expression and Its Prognostic Effect in Colorectal Adenocarcinoma Patients.

Background & Objective: Phosphatase and tensin homolog (PTEN) is a tumor suppressor gene located at chromosome 10. PTEN is a regulator of the PI3K/AKT signaling pathway that inhibits cell proliferation and promotes apoptosis. PTEN loss of function occurs in a spectrum of cancers, including colorectal adenocarcinoma. This study aimed to investigate the probable correlation of negative PTEN expression with clinicopathological features and colorectal adenocarcinoma (CRC) patients' survival. Methods: In this cross-sectional study using Immunohistochemistry stainingPTEN expression status on 151 CRC tissues was evaluated. Then the results of IHC staining was compared to those of clinicopathological features. The relationship between PTEN and KRAS mutation status was also investigated. Results: Of 151 CRC samples, 89 (58.9%) were negative for PTEN expression. Loss of PTEN expression was associated with KRAS mutation (P<0.0001), lymph node metastasis (P=0.002), and advanced tumor stage (P=0.016), whereas no significant association was found with other clinicopathological features. Multivariate analysis indicated that tumor site and KRAS mutation were independent prognostic CRC patients (P<0.05). The Kaplan-Meier analysis indicated a correlation between loss of PTEN expression and overall survival of patients with colorectal adenocarcinoma (P= 0.01). Conclusion: The current study suggests that decreasing PTEN expression or its negative expression may be associated with a higher stage and poor prognosis. Combined analysis of mutated KRAS and PTEN expression could be a good predictor of disease prognosis as well as its clinical outcomes.

Improvement of cytotoxicity of mitoxantrone and daunorubicin by candidone, tephrosin, and bavachinin.

BACKGROUND: Flavonoids have been demonstrated to have the ability of sensitizing cancer cells to chemotherapy and inverse multidrug resistance via various mechanisms, such as modulating of pumps. The therapeutic effect of candidone, tephrosin, and bavachinin in treatment of cancer, particularly to overcome multidrug resistance (MDR) is largely unknown. The capacity of these agents in sensitization of MDR cells is investigated in the current work. METHODS AND RESULTS: We analyzed the impact of candidone, tephrosin, and bavachinin, as chemosensitizer on cell cytotoxicity, P-gp and ABCG2 mRNA expression level on two multidrug resistant cells, ABCG2 overexpressing human epithelial breast cancer cell line (MCF7/MX), and P-gp overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB). The inhibitory concentration of 50% (IC50) of daunorubicin in EPG85.257RDB cells in combination with IC10 of Bavachinin, Tephrosin, and Candidone were 6159 ± 948, 4186 ± 665, 730 ± 258 nM, and this data in MCF7/MX cell were 1773 ± 534, 7160 ± 405 and 3340 ± 622 nM respectively. These three flavonoids dose-dependently decreased the viability of MCF7/MX and EPG85.257RDB and significantly (p < 0.05) decreased IC50 of daunorubicin and mitoxantrone except Tephrosin in MCF7/MX cells. Candidone and Bavachinin were the most potent chemosensitizer in EPG85.257RDB and MCF7/MX cells respectively. Flavonoids did not reduce mRNA expression of P-gp and ABCG2 after 72 h treatment, except Candidone in EPG85.257RDB and Bavachinin in MCF7/MX cells. CONCLUSIONS: This effect is not time-dependent, and flavonoids have their own patterns that are cell-dependent. In general, tephrosin, candidone, and bavachinin had the potential of sensitizing MDR cells to mitoxantrone and daunorubicin.

All-fiber spatiotemporally mode-locked laser with multimode fiber-based filtering.

We demonstrate the first all-fiber multimode spatiotemporally mode-locked laser. The oscillator generates dissipative soliton pulses at 1036 nm with 12 mW average power, 6.24 ps duration, and 24.3 MHz repetition rate. The reported pulse energy (0.5 nJ) represents ∼4 times improvement over the previously reported single-mode all-normal dispersion mode-locked lasers with multimode interference-based filtering. Numerical simulations are performed to investigate the cavity and spatiotemporal mode-locking dynamics. The all-fiber oscillator we present shows promise for practical use since it can be fabricated simply.

Characterization and Prospective Applications of the Exopolysaccharides Produced by Rhodosporidium babjevae.

Purpose: Due to the potential industrial and therapeutic applications of the yeast exopolysaccharides (EPSs), there has been an increasing demand to assess these biopolymers with improved characteristics. This study aimed to characterize the EPSs from Rhodosporidium babjevae (ATCC 90942 and IBRC-M 30088) as well as to evaluate their possible antioxidant, emulsifying and antiproliferative activities. Methods: Rhodosporidium babjevae was cultured for 5 days and following isolation of supernatant, EPSs precipitated with adding of cold absolute ethanol and freeze-dried. The EPSs chemical structure was determined by FT-IR, SEM, HPLC-SEC and GC-MS. Additionally the solubility, water holding capacity and emulsifying activity of EPSs were evaluated. In vitro, antioxidant activity was investigated against DPPH, superoxide and hydroxyl radicals. Finally the EPSs consequence on the cell proliferation of human breast adenocarcinoma (MCF-7) and Madin-Darby canine kidney (MDCK) cell lines was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. Results: R. babjevae excreted 1.6±0.2 g/L of the EPSs. The EPSs had three fractions with molecular weights of 1.02 ×106 , 5×105 and 2×105 Da. Mannose and glucose were found as the main monosaccharides of the EPSs (84:16 mol%, respectively). The EPSs exhibited emulsifying activity on sun flower oil. The scavenging activities were found to be dose-dependent and higher than hyaluronic acid. Significant difference among the EPSs treatments on the proliferation of MCF-7 and MDCK cell lines was not observed (P>0.05). Conclusion: These results show the interesting potential of the EPSs from R. babjevae as biocompatible compounds for using in food and pharmaceutical fields.

Resistance of human primary mesenchymal stem cells to cytotoxic effects of nutlin-3 in vitro.

BACKGROUND: The small-molecule nutlin-3 was found to be an effective therapeutic compound and p53 activator, and acts as a murine double minute 2 antagonist, although these findings need to be clinically confirmed. The essential components of the bone marrow include mesenchymal stem cells (MSCs), which play a key role in protecting, regenerating, and proliferating hematopoietic stem cells (HSCs). This feature is vital for HSC after exposure to myelotoxic anticancer agents; nevertheless, the effects of nutlin-3 on MSCs remain to be disclosed. The present research study was conducted to examine the antiproliferative and proapoptotic effectiveness of nutlin-3 in bone marrow MSCs (BMSCs). MATERIALS AND METHODS: Human-derived BMSCs were cultured for different durations, that is, 24, 48, and 72 hours, and treated using various concentrations of nutlin-3, including 5, 10, 25, 50, and 100 µΜ. To investigate the effect of nutlin-3 on the apoptosis, cell vitality and proliferation in BMSCs, the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), thiazolyl blue tetrazolium bromide, propidium iodide (PI) and annexin V assay, as well as real-time polymerase chain reaction, were used. RESULTS: BMSCs viability significantly decreased (P < .05) in the cells treated at concentrations of 50 and 100 µM for 24 hours and concentrations of 25, 50, and 100 µM for 48 hours and at all concentrations for 72 hours. The apoptosis of BMSCs (TUNEL positive) was significantly more visible at concentrations of 25 and 50 µM compared with that in the controls (P < .05), while this increased through dose-dependent processes. Annexin V/PI staining revealed negligible dose-dependent increases in all the apoptotic cells after 72 hours of incubation, and this apoptosis elevation was significant at 25 and 50 µM (P < .05). CONCLUSION: Resistance to nutlin-3 was observed in human bone marrow-derived MSCs; nevertheless, further clinical data are required to be obtained with long-duration exposure to confirm the present findings.

Enhancing the Therapeutic Efficacy of Daunorubicin and Mitoxantrone with Bavachinin, Candidone, and Tephrosin.

The capability of flavonoids in sensitizing cancer cells was demonstrated in numerous works to chemotherapy and converse multidrug resistance by modulating efflux pumps and apoptosis mechanisms. Three flavonoids, namely, bavachinin, tephrosin, and candidone, have been recently introduced to cancer treatment research presenting various activities, such as antibacterial, immunomodulatory, cell death, and anticancer. Less information exists regarding the therapeutic significance of these flavonoids in cancer treatment, especially in overcoming multidrug resistance (MDR). Here, we tempted to investigate the potency of these agents in reversing MDR by analyzing their effects as chemosensitizers on cell cytotoxicity, P-gp and ABCG2 protein expression levels, and their function on two multidrug-resistant cell lines, P-gp-overexpressing human gastric adenocarcinoma cell line (EPG85.257RDB) and ABCG2-overexpressing human epithelial breast cancer cell line (MCF7/MX). The inhibitory concentration of 10% (IC10) of bavachinin, tephrosin, and candidone in EPG85.257RDB cells was 1588.7 ± 202.2, 264.8 ± 86.15, and 1338.6 ± 114.11 nM, respectively. Moreover, these values in MCF7/MX cell were 2406.4 ± 257.63, 38.8 ± 4.28, and 27.9 ± 5.59 nM, respectively. Expression levels of ABCG2 and P-gp were not significantly downregulated by these flavonoids. Maximum levels of daunorubicin and mitoxantrone accumulations and minimum rates of drug efflux in both cell lines were detected 48 hrs posttreatment with tephrosin and bavachinin, respectively. Chemosensitization to mitoxantrone and daunorubicin treatments was, respectively, achieved in MCF7/MX and EPG85.257RDB cells in response to IC10 of bavachinin and tephrosin, independently. These effects did not follow time-dependent manner, and each flavonoid had its cell-dependent patterns. Overall, bavachinin, tephrosin, and candidone showed potency to sensitize MDR cells to daunorubicin and mitoxantrone and could be considered as attractive MDR modulators for cancer treatment. However, their action was time and cell specific.

Omega-3 PUFA Alters the Expression Level but Not the Methylation Pattern of the WIF1 Gene Promoter in a Pancreatic Cancer Cell Line (MIA PaCa-2).

Pancreatic cancer is the fourth leading cause of death in both males and females, with a 5-year relative survival rate of 8%. The Wnt signaling pathway has a significant role in the pathogenesis of many tumors, including those of pancreatic cancer. Hypermethylation of the Wnt inhibitory Factor-1 (WIF1) gene promoter have been detected in different types of cancer. In contrast, the anticancer effects of long-chain omega-3 PUFA (ALA) have been reported. Regarding its anticancer effects, in this study, we investigated the effects of various concentrations of omega-3 PUFA on expression level and promoter methylation of the WIF1 gene in MIA PaCa-2 cells in 24, 48, and 72 h after treatment. MIA PaCa-2 cells were treated with different concentrations of omega-3 PUFA (25, 50, 100, 250, 500, and 1000 µM). Cell viability assay was carried out followed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and methylation-specific PCR (MSP). This investigation suggested that dietary consumption of omega-3 PUFAs (250-1000 µM) has a significant effect on the proliferation and WIF1 gene expression of the MIA PaCa-2 cancer cell line but no effect on the promoter methylation of this gene. Changes in promoter methylation were not observed in any of the treatments.

Angiopoietin-like protein 8 (betatrophin) may inhibit hepatocellular carcinoma through suppressing of the Wnt signaling pathway.

OBJECTIVES: Hepatocellular carcinoma (HCC) is one of the leading fatal neoplasms and the most common primary liver malignancy worldwide. Peptide hormone ANGPTL8 (betatrophin) may act as an important regulator in HCC development through the Wnt/ß-catenin pathway. We aimed to evaluate the effects of recombinant ANGPTL8 on Wnt/ß-catenin signaling in human liver carcinoma cells (HepG2) and their viability. MATERIALS AND METHODS: The expression of ANGPTL8 was conducted in the pET-21b-E. coli Bl21 (DE3) system and the produced peptide was purified. HepG2 cells were treated with different concentrations of ANGPTL8 (25, 50, 100, 150, 200, and 250 ng/ml) for 24, 48, and 72 hr. MTT assay was performed to detect the viability of treated cells, and apoptotic induction by ANGPTL8 was measured by flow cytometry assay. Finally, using qRT-PCR the mRNA levels of Wnt signaling modulators WIF-1 and ß-catenin were evaluated in treated cells. RESULTS: MTT assay showed that ANGPTL8 inhibits proliferation of HepG2 cells moderately in a time-independent manner. The highest concentration of the ANGPTL8, 250 ng/ml, reduced cell proliferation after 24, 48, and 72 hr similarly about 30%. In the same concentration of ANGPTL8, after 24 hr of treatment flow cytometry assay revealed a mild increase in early and late apoptosis up to 7.7 and 14.3%, respectively. The qRT-PCR showed that in a concentration-dependent and time-independent fashion, the expression of WIF-1 and ß-catenin genes respectively increased and decreased significantly (P<0.05). CONCLUSION: Our findings suggest that ANGPTL8 may act as a moderate suppressor against HCC cell proliferation possibly via affecting Wnt signaling modulators.

The role of transferrin receptor in the Helicobacter pylori pathogenesis; L-ferritin as a novel marker for intestinal metaplasia.

Helicobacter pylori growth requirements is a prerequisite to invade gastric epithelium and the process of injury to gastric cells will eventually lead to gastric cancer. The aim of this study is to investigate the effect of iron challenge on the expression of genes involved in iron homeostasis. The presence of Phosphoglucosamine mutase (glmM), cytotoxin-associated gene A (cagA) and vacuolating cytotoxin A (vacA) genes and mRNA expression of Iron Regulatory Protein 2 (IRP2), Transferrin Receptor (TFRC) and Ferritin Light Chain (FTL) genes in samples of 28 normal gastric mucosa, 33 chronic gastritis, 29 gastritis with intestinal metaplasia, 29 intestinal type adenocarcinoma patients were examined by real-time PCR. Immunohistochemistry was used to analyze cellular localization and protein levels. In the all H. pylori positive tissues, particularly in the basal regions of foveolar cells, TFRC was overexpressed (P < 0.05), and regardless of the H. pylori infection, FTL was overexpressed in all patient, exclusively in metaplastic glandular cells (P < 0.05). Furthermore, overexpression of IRP2 was associated with H. pylori positive chronic gastritis and intestinal metaplasia (P < 0.05). Our findings confirm the role of transferrin receptor in H. pylori attachment into the gastric mucosa to capture iron. Overexpression of FTL gene in metaplastic cells could be considered as a research background to investigate the role of this gene in the differentiation of gastric cells into intestinal metaplasia. In addition, this gene could be suggested as a diagnostic marker to be included among the other markers routinely performed by clinical diagnostic laboratories.

Multimode optical fiber transmission with a deep learning network.

Multimode fibers (MMFs) are an example of a highly scattering medium, which scramble the coherent light propagating within them to produce seemingly random patterns. Thus, for applications such as imaging and image projection through an MMF, careful measurements of the relationship between the inputs and outputs of the fiber are required. We show, as a proof of concept, that a deep neural network can learn the input-output relationship in a 0.75 m long MMF. Specifically, we demonstrate that a deep convolutional neural network (CNN) can learn the nonlinear relationships between the amplitude of the speckle pattern (phase information lost) obtained at the output of the fiber and the phase or the amplitude at the input of the fiber. Effectively, the network performs a nonlinear inversion task. We obtained image fidelities (correlations) as high as ~98% for reconstruction and ~94% for image projection in the MMF compared with the image recovered using the full knowledge of the system transmission characterized with the complex measured matrix. We further show that the network can be trained for transfer learning, i.e., it can transmit images through the MMF, which belongs to another class not used for training/testing.

Effect of calprotectin subunit S100A9 on the expression and methylation of OCLN in human melanoma cell line A-375.

Increased levels of calprotectin subunits S100A8 and S100A9 have been detected in human cancers. Melanoma is the most aggressive type of skin cancer, and its treatment is challenging because of its brain metastasis. OCLN encodes occluding, which plays a major role in the formation and regulation of tight junctions. The aim of this study was to evaluate the methylation status of the OCLN promoter and its expression in A-375 melanoma cells treated with or without various concentrations of S100A9 for 24, 48, and 72 h. Total RNA was extracted, and synthesized cDNA was assessed by performing real-time PCR. MSP-PCR was performed after treatment with bisultfie. Recombinant S100A9 inhibited the proliferation of the A-375 cell line and the expression of the OCLN gene was downregulated in a time- and concentration-dependent manner. Results of MSP-PCR showed that the OCLN gene promoter in a human melanoma cell line (A-375) was semimethylated.

Mutation screening in the mitochondrial D-loop region of tumoral and non-tumoral breast cancer in Iranian patients.

The mitochondrial DNA (mtDNA) mutations in mitochondrial coding and non coding regions seem to be important in carcinogenesis. The aim of this investigation was to evaluate coding region (mt-tRNA(Phe) and tRNA(Pro)) and non-coding sequence, mitochondrial displacement loop (mtDNA D-loop), in the cancerous and non-cancerous lesions of Iranian patients with breast cancer (BC). Genomic DNA was extracted from 50 breast tumors and surrounding normal tissue pairs as well as from 50 unrelated normal breast tissues from Iranian Kurdish population. Subsequently, PCR amplification was performed using specific primers, and then PCR products were subjected to direct sequencing. 41 genetic variants were identified in mtDNA D-loop among tumoral and non-tumoral tissues but not in tRNA(Phe) and tRNA(Pro) sequences. Our findings indicated that C182T, 194insT, 285insA and 16342delT were just found in BC tumors whereas 302insC, C309T and C16069T found in both tumors and surrounding normal tissues. Although our findings showed that the observed genetic variations were not restricted to breast cancer tissues, some genetic changes were found only in BC tumors. Our results, in agreement with the evidence from earlier studies, confirm that the mtDNA genetic alterations might be implicated in tumor initiation, progression and development.