Macrophage polarity in cancer: A review.

Macrophages are the most abundant cells within the tumor stroma displaying noticeable plasticity, which allows them to perform several functions within the tumor microenvironment. Tumor-associated macrophages commonly refer to an alternative M2 phenotype, exhibiting anti-inflammatory and pro-tumoral effects. M2 cells are highly versatile and multi-tasking cells that directly influence multiple steps in tumor development, including cancer cell survival, proliferation, stemness, and invasiveness along with angiogenesis and immunosuppression. M2 cells perform these functions through critical interactions with cells related to tumor progression, including Th2 cells, cancer-associated fibroblasts, cancer cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells. M2 cells also have negative cross-talks with tumor suppressor cells, including cytotoxic T cells and natural killer cells. Programed death-1 (PD-1) is one of the key receptors expressed in M2 cells that, upon interaction with its ligand PD-L1, plays cardinal roles for induction of immune evasion in cancer cells. In addition, M2 cells can neutralize the effects of the pro-inflammatory and anti-tumor M1 phenotype. Classically activated M1 cells express high levels of major histocompatibility complex molecules, and the cells are strong killers of cancer cells. Therefore, orchestrating M2 reprogramming toward an M1 phenotype would offer a promising approach for reversing the fate of tumor and promoting cancer regression. Macrophage switching toward an anti-inflammatory M1 phenotype could be used as an adjuvant with other approaches, including radiotherapy and immune checkpoint blockades, such as anti-PD-L1/PD-1 strategies.

Holographic direct sound printing.

Direct sound printing (DSP), an alternative additive manufacturing process driven by sonochemical polymerization, has traditionally been confined to a single acoustic focal region, resulting in a voxel-by-voxel printing approach. To overcome this limitation, we introduce holographic direct sound printing (HDSP), where acoustic holograms, storing cross-sectional images of the desired parts, pattern acoustic waves to induce regional cavitation bubbles and on-demand regional polymerization. HDSP outperforms DSP in terms of printing speed by one order of magnitude and yields layerless printed structures. In our HDSP implementation, the hologram remains stationary while the printing platform moves along a three-dimensional path using a robotic arm. We present sono-chemiluminescence and high-speed imaging experiments to thoroughly investigate HDSP and demonstrate its versatility in applications such as remote ex-vivo in-body printing and complex robot trajectory planning. We showcase multi-object and multi-material printing and provide a comprehensive process characterization, including the effects of hologram design and manufacturing on the HDSP process, polymerization progression tracking, porosity tuning, and robotic trajectory computation. Our HDSP method establishes the integration of acoustic holography in DSP and related applications.

Ecosystem services valuation: a review of concepts, systems, new issues, and considerations about pollution in ecosystem services.

Managers can determine the function of ecosystem services in decision-making processes through valuation. Ecological functions and processes that benefit people lead to ecosystem services. Valuing ecosystem services mean finding values for the benefits of ecosystem services. For the concepts related to ecosystem services and their valuation, categories in different articles have been presented. One of the most important issues is providing a suitable grouping for different methods and concepts of valuing ecosystem services. In this study, the most recent topics related to ecosystem service valuation methods were compiled and categorized by using the system theory. The aim of this study was to introduce some of the most important classical and modern methods and concepts of valuing ecosystem services. For this aim, a review of articles related to ecosystem service valuation methods, content analysis, and categorization of their contents was used to provide definitions, concepts, and categorization of different methods. To summarize, valuation methods are classified into two types: classical and modern methods. Classical approaches include the avoided cost method, the replacement cost method, the factor income method, the travel cost method, hedonic pricing, and contingent value. Modern methods include the basic value transfer method, deliberative ecosystem service valuation, valuation of climate change risks, and other cases that evolve every day in the world of science. Findings of the paper have the potential to be beneficial in comprehending the definitions and ideas of ecosystem services in ecosystem management, particularly in protected areas, participatory management, and pollutant research. This research can add to the worldwide literature on the valuing of ecosystem services while also determining the most pressing issues and difficulties of today, such as climate change, pollution, ecosystem management, and participatory management.

Direct sound printing.

Photo- and thermo-activated reactions are dominant in Additive Manufacturing (AM) processes for polymerization or melting/deposition of polymers. However, ultrasound activated sonochemical reactions present a unique way to generate hotspots in cavitation bubbles with extraordinary high temperature and pressure along with high heating and cooling rates which are out of reach for the current AM technologies. Here, we demonstrate 3D printing of structures using acoustic cavitation produced directly by focused ultrasound which creates sonochemical reactions in highly localized cavitation regions. Complex geometries with zero to varying porosities and 280 µm feature size are printed by our method, Direct Sound Printing (DSP), in a heat curing thermoset, Poly(dimethylsiloxane) that cannot be printed directly so far by any method. Sonochemiluminescnce, high speed imaging and process characterization experiments of DSP and potential applications such as remote distance printing are presented. Our method establishes an alternative route in AM using ultrasound as the energy source.

Infertility cell therapy and epigenetic insights.

Recent advances in assisted reproductive technology (ART) have allowed couples with severe infertility to conceive, but the methods are not effective for all cases. Stem cells as undifferentiated cells which are found in different stages of embryonic, fetal and adult life are known to be capable of forming different cell types, tissues, and organs. Due to their unlimited resources and the incredible power of differentiation are considered as potential new therapeutic biological tools for treatment of infertility. For reproductive medicine, stem cells are stimulated in vitro to develop various specialized functional cells including male and female gametes. The epigenetic patterns can be modified in the genome under certain drugs exposure or lifestyle alterations. Therefore, epigenetics-related disorders may be treated if the nature of the modifications is completely admissible. It is proved that our understanding of epigenetic processes and its association with infertility would help us not only to understand the etiological factors but also to treat some type of male infertilities. Exploration of both genetic and epigenetic variations in the disease development could help in the identification of the interaction patterns between these two phenomena and possible improvement of therapeutic methods.

Association between tumor necrosis factor-alpha gene rs1800629 (-308G/A) and rs361525 (-238G > A) polymorphisms and prostate cancer risk in an Iranian cohort.

BACKGROUND: Prostate cancer (PCa) as the first men's common cancer in the world and the third cancer in Iranian men is a heterogeneous disorder which sometimes several biopsies are needed for its diagnosis. OBJECTIVES: The aim of current study is finding new biomarkers in order to diagnose of PCa at the earliest possible stage. Hence, the relationship between rs1800629 and rs361525 polymorphisms of TNF-α gene with PCa was investigated. MATERIALS AND METHODS: Blood DNA samples were collected from 100 patients with PCa, 110 with BPH, and 110 controls. Collected samples were examined using PCR-RFLP and Tetra-ARMS-PCR techniques to detect the desired polymorphisms. RESULTS: The frequency of rs1800629 genotypes in smokers was significantly different from non-smokers with PCa (p= 0.001). Logistic regression analysis results showed that GA heterozygotes in comparison to GG homozygotes had higher risk of developing Benign Prostatic Hyperplasia (BPH) or prostate cancer. However, no significant correlation was considered between the risk of PCa and the TNF-α gene polymorphisms (rs1800629 and rs361525). CONCLUSIONS: Although, the achieved results of this investigation demonstrated that the two examined genetic variants do not seem to be suitable markers for early diagnosis of prostate cancer in this pilot study; however increased risk for the disease is shown in GA heterozygotes and smokers which is indicative of some epigenetic factors influence on prostate cancer etiology.

Investigating the relationship between ccfDNA concentration, its integrity, and some individual factors in an Iranian population.

INTRODUCTION: Circulating cell-free DNA (ccfDNA) increases in some pathologic conditions like cancer. We aimed to investigate the correlation between some individual factors and the ccfDNA level in peripheral blood of Iranian in relation to prostate cancer. MATERIAL AND METHOD: 30 patients with prostate cancer (PCa), 40 with benign prostate hyperplasia (BPH), and 30 controls were studied. Personal information, ccfDNA concentration, and the integrity index were assessed for the correlation between the disease and different factors. The results were statistically analyzed using SPSS software. RESULTS: In PCa group, no association was found between total ccfDNA, BMI, BPH background, non-cancerous diseases, medications, PCa length, and job (p-value > 0.05). But, total ccfDNA had statistical associations with weight, family history of cancer, and location (p-value < 0.05). No association was between the integrity of ccfDNA, weight, the background of BPH, and family history of cancer. But, the integrity of ccfDNA was significantly associated with BMI and PCa length (p-value < 0.05).In BPH group, no association between total ccfDNA or the integrity of ccfDNA and the assessed factors was obtained (p-value > 0.05). In the normal group, neither statistical association was found between total ccfDNA, weight, BMI, and job, nor between the integrity of ccfDNA, weight, BMI, non-cancerous disease, drug, job, and location (p-value > 0.05). But, a statistical association was found between the integrity of ccfDNA and family history of cancer in the recent group (Based on 95% CI and P-value less than 0.05). CONCLUSION: ccfDNA and its integrity as possible prostate cancer biomarkers under the influence of individuals' physiological status are prone to the pathologic changes toward the disease. Further simultaneous study of the target groups could clarify this matter.

The Importance of Small Non-Coding RNAs in Human Reproduction: A Review Article.

BACKGROUND: MicroRNAs (miRNA) play a key role in the regulation of gene expression through the translational suppression and control of post-transcriptional modifications. AIM: Previous studies demonstrated that miRNAs conduct the pathways involved in human reproduction including maintenance of primordial germ cells (PGCs), spermatogenesis, oocyte maturation, folliculogenesis and corpus luteum function. The association of miRNA expression with infertility, polycystic ovary syndrome (PCOS), premature ovarian failure (POF), and repeated implantation failure (RIF) was previously revealed. Furthermore, there are evidences of the importance of miRNAs in embryonic development and implantation. Piwi-interacting RNAs (piRNAs) and miRNAs play an important role in the post-transcriptional regulatory processes of germ cells. Indeed, the investigation of small RNAs including miRNAs and piRNAs increase our understanding of the mechanisms involved in fertility. In this review, the current knowledge of microRNAs in embryogenesis and fertility is discussed. CONCLUSION: Further research is necessary to provide new insights into the application of small RNAs in the diagnosis and therapeutic approaches to infertility.

The value of the plasma circulating cell-free DNA concentration and integrity index as a clinical tool for prostate cancer diagnosis: a prospective case-control cohort study in an Iranian population.

Introduction: Prostate cancer (PCa) is the most common cancer among men and the second cause of cancer death among men. For early detection and differentiating PCa from benign prostate hyperplasia (BPH) tissue biopsy has been used for decades. However, circulating cell-free DNA (ccfDNA) testing is a noninvasive, fast, easily repeatable, and sensitive liquid biopsy for cancer detection. Hence, we aimed to investigate the value of the ccfDNA concentration and integrity index in peripheral blood of a population of Iranian prostatic patients for early diagnosis of the disease. Materials and methods: 100 subjects including 30 PCa, 40 BPH, and 30 healthy individuals were selected. ccfDNA was extracted from fresh blood plasma, and its total concentration and the integrity index were estimated by amplification of ALU115 and ALU247 repeat elements using quantitative real-time PCR. Results: In the PCa group, the ccfDNA concentration and its integrity were significantly higher than that of the BPH and healthy groups (P-value <0.001 and P-value <0.001). The ccfDNA concentration and its integrity were higher in BPH compared to the healthy group, although it was not statistically significant (P-value =0.836 and P-value =0.053, respectively). Conclusion: A significant relation between ccfDNA concentration, its integrity, and PCa suggests that the liquid biopsy can be used as a noninvasive early diagnostic biomarker. Determination of a cutoff or a diagnostic range value of the measured parameters for healthy, BPH, and PCa subjects in more samples of Iranian population results in timely, correct, and early detection, which results in better treatment outcomes. Moreover, this method may reduce overdiagnosis and overtreatment procedures.

Premutations of FMR1 CGG repeats are not related to idiopathic premature ovarian failure in Iranian patients: A case control study.

Premature ovarian failure (POF) is a reproductive disease which affects 1 in 100 under 40 years women. FMR1 premutation carriers of CGG repeats are supposed to be at increased risk for POF. We have examined the 5'UTR region of the gene to find any association between the repeat size and the disease etiology in Iranian population. 30 women with early idiopathic POF and 30 fertile control women were selected. We used triplet repeat primed PCR (TP PCR) assay and gene-specific primers to amplify the CpG Island of FMR1 gene promoter region. The amplification results were analyzed by capillary electrophoresis and Gene Marker software. Among 30 patients, two had intermediate repeat size, one had premutation and the rest had CGG repeat of the normal range. Two of controls had intermediate repeats and none had a premutation. Two groups had significant differences in the repeat number average (p = 0.007) and in the average length of the smallest allele (p < 0.001), but had no promising difference in average length of the longest allele (p = 0.453). Although the two groups showed a significant difference in the length of alleles, their length was within normal range. Perhaps the polymorphism, in connection with the genome's entire network, has been involved in the development of the disease, or there has been a fundamentally different mechanism for the disease in Iranian population. A larger number of Iranian POF patients should be investigated for any probable relationship between the CGG triplet repeat length and the etiology of the disease.

Genetic variations in UGT2B28, UGT2B17, UGT2B15 genes and the risk of prostate cancer: A case-control study.

Glucuronidation is a major pathway for elimination of exogenous and endogenous compounds such as environmental carcinogens and androgens from the body. This biochemical pathway is mediated by enzymes called uridine diphosphoglucuronosyltransferases (UGTs). Null (del/del) genes polymorphisms in UGT2B17, and UGT2B28 and D85Y single-nucleotide polymorphism (SNP) of UGT2B15 have been reported to increase the risk of prostate cancer. The goal of this study was to determine the association of mentioned genetic variants with the risk of prostate cancer. We investigated the copy number variations (CNVs) of UGT2B17 and UGT2B28 loci and the association between rs1902023 polymorphism of UGT2B15 gene in 360 subjects consisted of 120 healthy controls, 120 prostate cancer (PC) patients and 120 benign prostatic hyperplasia (BPH) patients. No association was detected for the mentioned polymorphisms and the risk of PC. However, a significant association was detected between UGT2B17 copy number variation and BPH risk (OR=2.189; 95% CI, 1.303-3.675; p=0.003). Furthermore, we observed that the D85Y polymorphism increases the risk of BPH when analyzed in combination with the copy number variation of UGT2B17 gene (OR=0.135; 95% CI, 0.036-0.512; p=0.003). Our findings suggest that the D85Y polymorphism of UGT2B15 and CNVs in UGT2B28 and UGT2B17 genes is not associated with prostate cancer risk in Iranian patients. To our knowledge, this is the first report that implicates the role of CNV of UGT2B17 gene in BPH.

Association study of the vesicular monoamine transporter 1 (VMAT1) gene with autism in an Iranian population.

Autism Spectrum Disorders (ASD) (MIM 209850) are a group of neurodevelopmental disorders distinguished by destructed social interaction and communication abilities along with peculiar repetitive behavior. Several genetic loci have been linked to this disorder. Vesicular monoamine transporter 1 (VMAT1/SLC18A1) is an attractive candidate gene for psychiatric disorders because of its participation in regulation monoamines. In the present case-control study, we evaluated the link between three non-synonymous single nucleotide polymorphisms (SNPs) (rs2270641 [Pro4Thr], rs2270637 [Thr98Ser] and rs1390938 [Thr136Ile]) and one intronic SNP (rs2279709) across the VMAT1 gene and ASD in a group of Iranian patients. Allele frequency analyses showed significant over-presentation of rs1390938-G allele in cases compared with controls (P<0.001). The analysis under different genetic models showed that the AA genotype of the rs1390938 was protective against ASD under dominant and recessive models. The rs2270641 SNP was associated with ASD risk only in over-dominant model. Other SNPs showed no significant difference in allele or genotype frequencies between two groups. Haplotype analysis revealed that C A T T and C A T G haplotypes (rs2270637, rs1390938, rs2279709 and rs2270641 respectively) have a protective effect against ASD. Consequently, the functional rs1390938 SNP in VMAT1 is associated with ASD in Iranian population. Considering the role of VMAT1 in regulation of monoamines, the dysregulated expression of this protein during early stages of brain development might be implicated in ASD.

HOTAIR genetic variants are associated with prostate cancer and benign prostate hyperplasia in an Iranian population.

Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with a wide array of clinical presentations and high prevalence among men. Several protein coding genes as well as non-coding genes have been shown to contribute in prostate cancer and BPH risk. Among non-coding genes whose contribution in tumorigenesis has been identified is HOX transcript antisense RNA (HOTAIR). In the present study we aimed at identification of the associations between three HOTAIR polymorphisms (rs12826786, rs1899663 and rs4759314) and risk of prostate cancer and BPH by the means of tetra-primer ARMS-PCR in a population of 128 Iranian prostate cancer patients, 143 BPH patients and 250 normal male controls. The study showed that rs1899663 T allele was associated with BPH risk. Comparison between prostate cancer and BPH groups showed that rs1899663 is associated with cancer risk in co-dominant, dominant and recessive inheritance models. The rs12826786 T allele was significantly more presented in both BPH and prostate cancer groups compared with healthy subjects. This SNP was associated with both BPH and prostate cancer risk in co-dominant and recessive models. However, rs4759314 showed no significant difference in allele or genotype frequencies between three mentioned groups. In addition, some haplotypes within this gene were associated with increased prostate cancer and BPH risk. Consequently, HOTAIR can be suggested as a risk locus for prostate cancer and BPH in Iranian population.

The Importance of VEGF-KDR Signaling Pathway Genes should Not Be Ignored When the Risk of Developing Multiple Sclerosis is Taken into Consideration.

Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) pathway trigger the process of angiogenesis as well as inflammation, which contributes to the development and progression of demyelinating lesions in multiple sclerosis. This work is a case-control study comprising of a total of 400 subjects with multiple sclerosis and 400 healthy controls. Participants were subjected to neurological examination and peripheral blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A significantly higher frequency of the T allele and TT genotype of the VEGF 936C > T (rs3025039) polymorphism was found in the multiple sclerosis group than in the healthy control group (P = 0.01 [OR = 1.41] and P = 0.01 [OR = 3.12], respectively). In addition, VEGF 936C  >  T showed an association with patients in a recessive model. However, the KDR -604T > C (rs2071559) polymorphism showed no significant difference in either allelic or genotype frequency between the two groups. Taken together, the results of the present study suggests that the T allele of the rs3025039 in VEGF gene could be considered a risk factor for developing multiple sclerosis in the Iranian population.

Association of ANRIL gene polymorphisms with prostate cancer and benign prostatic hyperplasia in an Iranian population.

AIM: Prostate cancer and benign prostate hyperplasia (BPH) are heterogeneous disorders with high prevalence among men. The antisense noncoding RNA in the INK4 locus codes for a long noncoding RNA whose participation in cancer has been elucidated. METHOD: We analyzed rs1333045, rs4977574, rs1333048 and rs10757278 genotypes from this locus in 125 prostate cancer patients, 125 BPH patients as well as 220 normal age-matched subjects by means of tetra-primer amplification refractory mutation system PCR method. RESULTS: The rs1333045 showed no significant difference in allele or genotype frequencies between three groups. However, the other three single nucleotide polymorphisms have been shown to be associated with BPH and prostate cancer risk. CONCLUSION: Antisense noncoding RNA in the INK4 locus possibly participates in the pathogenesis of these disorders.

Radiation-induced nausea and vomiting: Is ABO blood group as important as radiation and patient-related factors? An observational study.

Despite the improvements in cancer screening and treatment, it still remains as one of the leading causes of mortality worldwide. Nausea and vomiting as the side effects of different cancer treatment modalities, such as radiotherapy, are multifactorial and could affect the treatment continuation and patient quality of life. Therefore, the aim of this study was to assess the possible linkage between ABO blood groups and radiation-induced nausea and vomiting (RINV), also its incidence and affecting factors.One hundred twenty-eight patients referring to Tohid hospital of Sanandaj, Iran, were selected and the patients and treatment-related factors were determined in a cross-sectional study. Patients' nausea and vomiting were recorded from the onset of treatment until 1 week after treatment accomplishment. Also, previous possible nausea and vomiting were recorded. The frequencies of nausea and vomiting and their peak time were examined during the treatment period.The association between ABO blood group and the incidence of radiotherapy-induced nausea and vomiting (RINV) were significant and it seems that A blood group patients are the most vulnerable individuals to these symptoms. The association between Rhesus antigen and the time of maximum severity of RINV may indicate that Rhesus antigen affects the time of maximum severity of RINV. The incidence of RINV was not affected by karnofsky performance status, but it was related to the severity of RINV. Furthermore, among the factors affecting the incidence of nausea and vomiting, nausea and vomiting during patient's previous chemotherapy, radiotherapy region, and background gastrointestinal disease were shown to be three important factors.In addition to familiar RINV-affecting factors, ABO blood group may play an important role and these results address the needs for further studies with larger sample size.

Effects of daily milk supplementation on improving the physical and mental function as well as school performance among children: results from a school feeding program.

BACKGROUND: School feeding programs are important interventions for improving the nutritional status of students. Therefore, this study was conducted to evaluate the effects of milk supplementation on physical, mental and school performance of students. METHODS: This case-control population-based intervention was conducted on 469 students from 4 schools in a medium socio-economic status region in Tehran. The schools were chosen by Iranian ministry of education and training and they were allocated in case and control groups randomly. All the students in the first to third classes in the intervention schools were daily consumed sterilized and homogenized milk for three months (250 ml each). Anthropometric measurements were done according to the standard methods. For evaluating the mental function, the Raven's Coloured Progressive Matrices (CPM) and Wechsler Intelligence Scale for children (verbal, non-verbal, total Intelligent Quotient) were conducted on students. School performance was assessed by grade-point averages of each student. RESULTS: The weight of children was significantly different between control and intervention group at the end of the study among girls (23.0 ± 3.8 vs. 23.8 ± 4.3 kg; p < 0.05). Psychological tests' scores were significantly different between the control and the intervention groups (p < 0.05) at the end of the trial among boys. The grade-point average was significantly different at the end of the trial between the intervention and the control group among girls (p < 0.05). CONCLUSIONS: School feeding programs focus on milk supplementation had beneficial effects on the physical function and school performances specifically among girls in Iran.