Machine learning algorithms for diagnosis of hip bone osteoporosis: a systematic review and meta-analysis study.

BACKGROUND: Osteoporosis is a significant health problem in the skeletal system, associated with bone tissue changes and its strength. Machine Learning (ML), on the other hand, has been accompanied by improvements in recent years and has been in the spotlight. This study is designed to investigate the Diagnostic Test Accuracy (DTA) of ML to detect osteoporosis through the hip dual-energy X-ray absorptiometry (DXA) images. METHODS: The ISI Web of Science, PubMed, Scopus, Cochrane Library, IEEE Xplore Digital Library, CINAHL, Science Direct, PROSPERO, and EMBASE were systematically searched until June 2023 for studies that tested the diagnostic precision of ML model-assisted for predicting an osteoporosis diagnosis. RESULTS: The pooled sensitivity of univariate analysis of seven studies was 0.844 (95% CI 0.791 to 0.885, I2 = 94% for 7 studies). The pooled specificity of univariate analysis was 0.781 (95% CI 0.732 to 0.824, I2 = 98% for 7 studies). The pooled diagnostic odds ratio (DOR) was 18.91 (95% CI 14.22 to 25.14, I2 = 93% for 7 studies). The pooled mean positive likelihood ratio (LR+) and the negative likelihood ratio (LR-) were 3.7 and 0.22, respectively. Also, the summary receiver operating characteristics (sROC) of the bivariate model has an AUC of 0.878. CONCLUSION: Osteoporosis can be diagnosed by ML with acceptable accuracy, and hip fracture prediction was improved via training in an Architecture Learning Network (ALN).

Socioeconomic status and metabolic syndrome in Southwest Iran: results from Hoveyzeh Cohort Study (HCS).

BACKGROUND: Socioeconomic status (SES) strongly predicts morbidity and premature mortality, especially for non-communicable diseases (NCDs). However, the effect of these factors on Metabolic Syndrome (MetS) is not clear yet. This study was conducted to assess the relationship between socioeconomic indicators and MetS. METHODS: In this prospective cohort study, 10,009 people aged 35-70 enrolled from May 2016 to August 2018. The MetS was defined according to The Standard National Cholesterol Education Program (NCEP)-adult treatment panel III (ATP III) or NCEP-ATP III criteria. Demographics and socioeconomic data were gathered face-to-face through trained interviews. Also, lab, anthropometrics, and blood pressure measurements were assayed for participants. Logistic regression was used to estimate the association between SES and MetS, adjusted for the potential confounding factors. RESULTS: The overall prevalence of MetS in the participants was 39.1%. The crude odds ratios were statistically significant for all the assessed variables (p < 0.05). After adjustment for age, sex, physical activity, smoking, and alcohol use as potential confounders, the results indicated significant direct independent associations between skill level (p = 0.006) and Townsend index (p = 0.002) with MetS. In contrast, no significant associations between educational level and wealth status with MetS. CONCLUSION: The results of our study showed that SES is related to MetS. Among the four assessed SES indicators, skilled levels and Townsend score are strongly associated with MetS. We recommend considering people's SES when interventional programs are planned and conducted on MetS in similar communities.

Bone Using Stem Cells for Maxillofacial Bone Disorders: A Systematic Review and Meta-analysis.

Due to economic, cultural, environmental, and social factors, the prevalence of maxillofacial bone disorders varies in different parts of the world. The present meta-analysis was conducted to assess the efficacy and safety of different type of stem cells-based scaffolds and their construction methods in maxillofacial bone disorders. We searched major indexing databases, including PubMed/Medline, ISI Web of Science, Scopus, Embase, and Cochrane Central without any language, study region, or type restrictions. A systematic search of articles published up to July 2021 was done. Of the 428 studies found through initial searches, 36 met the inclusion criteria. After applying the exclusion criteria, the main properties of 32 articles on 643 animals and 4 experimental studies on 52 patients (age range from 43 to 74 years) included in this meta-analysis. Our pooled analysis showed that stem cells-based scaffolds significantly improved the bone regeneration and formation in maxillofacial bone disorders (Prevalence: 0.54; 95% CI: 0.43, 0.64, P < 00001, I2 = 90 2). According to the results of these studies, in most studies, bone marrow-derived mesenchymal stem cells (BMSCs) have been used to regenerate bone, and these cells are still the gold standard in bone tissue engineering, a growth factor that is one of the three sides of the tissue engineering triangle. Bone morphogenetic proteins (BMP) especially BMP2 and platelet-rich plasma (PRP) are the most widely used growth factor and scaffold respectively. Platelet-rich plasma (PRP) is used as a scaffold and since it contains proteins, it also used as a growth factor and can be a stimulant of ossification. It seems that the future perspective of bone tissue engineering is to use the prototyping rapid method to build a composite and patient-specific scaffold from CT and MRI images, along with genetically modified stem cells.

The Probable Protective Effect of Photobiomodulation on the Inflammation of the Airway and Lung in COVID-19 Treatment: A Preclinical and Clinical Meta-Analysis.

Preliminary studies also show that many of the fatalities of COVID-19 are due to over-activity of the immune system, and photobiomodulation (PBM) therapy mainly accelerates wound healing and reduces pain and inflammation. Therefore, this systematic review and meta-analysis was conducted to evaluate the probable effect of the PBM therapy on the lung inflammation or ARDS and accelerate the regeneration of the damaged tissue. We systematically searched major indexing databases, including PubMed/Medline, ISI web of science (WOS), Scopus, Embase, and Cochrane central, using standard terms without any language, study region, or type restrictions. Of the 438 studies found through initial searches, 13 met the inclusion criteria. After applying the exclusion criteria, the main properties of 13 articles on 384 animals included in this meta-analysis with a wide range of species include rat (n = 10) and rabbit (n = 3). The analysis revealed that PBM therapy reduced TNFα (SMD:-3.75, 95% CI: -4.49, -3.02, P < 0.00001, I2 = 10%), IL-1ß (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%), and IL-6 (SMD:-4.20, 95% CI: -6.42, -1.97, P = 0.0002, I2 = 88%) significantly compared with the model controls. Hence, PBM therapy increased IL-10 significantly compared with the model controls (SMD:-4.65, 95% CI: -6.15, -3.16, P < 0.00001, I2 = 62%). PBM therapy also reduced MPO activity (SMD:-2.13, 95% CI: -3.38, -0.87, P = 0.0009, I2 = 64%) and vascular permeability (SMD:-2.59, 95% CI: -4.40, -0.77, P = 0.0052, I2 = 71%) in the lung using the Evans blue extravasation technique significantly compared with the model controls. This systematic review and meta-analysis revealed that the PBM therapy does utilize beneficial anti-inflammatory effect, modulation of the immune system, lung permeability, or bronchoalveolar lavage on lung damage in both animal models and clinical studies. However, animal model and clinical studies appear limited considering the quality of the included evidences; therefore, large clinical trials are still required.

Diagnostic performance of classification trees and hematological functions in hematologic disorders: an application of multidimensional scaling and cluster analysis.

BACKGROUND: Several hematological indices have been already proposed to discriminate between iron deficiency anemia (IDA) and ß-thalassemia trait (ßTT). This study compared the diagnostic performance of different hematological discrimination indices with decision trees and support vector machines, so as to discriminate IDA from ßTT using multidimensional scaling and cluster analysis. In addition, decision trees were used to determine the diagnostic classification scheme of patients. METHODS: Consisting of 1178 patients with hypochromic microcytic anemia (708 patients with ßTT and 470 patients with IDA), this cross-sectional study compared the diagnostic performance of 43 hematological discrimination indices with classification tree algorithms and support vector machines in order to discriminate IDA from ßTT. Moreover, multidimensional scaling and cluster analysis were used to identify the homogeneous subgroups of discrimination methods with similar performance. RESULTS: All the classification tree algorithms except the LOTUS tree algorithm showed acceptable accuracy measures for discrimination between IDA and ßTT in comparison with other hematological discrimination indices. The results indicated that the CRUISE and C5.0 tree algorithms had better diagnostic performance and efficiency among other discrimination methods. Moreover, the AUC of CRUISE and C5.0 tree algorithms indicated more precise classification with values of 0.940 and 0.999, indicating excellent diagnostic accuracy of such models. Moreover, the CRUISE and C5.0 tree algorithms showed that mean corpuscular volume can be considered as the main variable in discrimination between IDA and ßTT. CONCLUSIONS: CRUISE and C5.0 tree algorithms as powerful methods in data mining techniques can be used to develop accurate differential methods along with other laboratory parameters for the discrimination of IDA and ßTT. In addition, the multidimensional scaling method and cluster analysis can be considered as the most appropriate techniques to determine the discrimination indices with similar performance for future hematological studies.

The worldwide molecular spectrum and distribution of thalassaemia: a systematic review.

CONTEXT: Thalassaemia is one of the most common inherited autosomal recessive disorders around the world. A considerable amount of literature has been published about the type of mutations and the prevalence of thalassaemia, but findings are often contradictory. OBJECTIVE: This systematic review aimed to provide a comprehensive view of the prevalence of thalassaemia-associated mutations in different countries, their effect on haemoglobin (Hb) levels, as well as reporting thalassaemia-associated rare mutations. METHODS: A systematic search of the literature was carried out through major indexing databases (MEDLINE/PubMed, Scopus, EMBASE, Cochrane central, and ISI web of science) using keywords: "Co-inheritance, αα, ß, thalassaemia" and "α-ß thalassaemia, Mediterranean anemia, mutations" from 1998-September 2019. Hand-searching was also performed. There was no language restriction. RESULTS: The initial searches yielded 1059 studies, of which 92 articles were included following inclusion and exclusion criteria. Of these, 3.3% (3) of articles were cohort studies, and 96.7% (89) of the remaining articles were cross-sectional studies. Our findings showed that 45.6% (42) of researchers investigated ß-thalassaemia, 22.9% (21) αα-ß thalassaemia, and 31.5% (29) α thalassaemia. CONCLUSION: The present study provides valuable information about the spectrum of thalassaemia-associated mutations, which can be useful for preventing thalassaemia, reducing costs of care, reducing the treatment-related side effects, and showing the most defective mutations.HighlightEvaluating the increase or decrease in the birth prevalence of thalassaemiaIdentifying the most common and rare mutations in various parts of the worldComparing researchers' findings from various parts of the world.

Safety and efficacy of tocilizumab for rheumatoid arthritis: a systematic review and meta-analysis of clinical trial studies.

The present systematic review and meta-analysis was conducted to assess the effect of tocilizumab (TCZ) in patients with rheumatoid arthritis (RA). We systematically searched all potential articles in the main databases, including PubMed, Scopus, EMBASE, Web of Sciences (ISI), and Cochrane Center. The search was subsequently updated in December 2020. The initial review and extraction of information were performed independently by two authors to collect the first author and publication year; sample size; mean age of the intervention and control groups; the dose of TCZ, and the follow-up duration. Outcomes of interest include the ACR20, ACR50, ACR70, total complication rate, and the occurrence of remission. Any disagreements between the reviewers were resolved by discussion and re-check of the article and consultation with a third reviewer. After reviewing and culling, 15 clinical trials comparing the clinical efficacy of TCZ and its comparators in the treatment of patients with RA entered the qualitative and quantitative synthesis. Tocilizumab 8 mg was statistically better than 4 mg or placebo for ACR responses. Significant clinical adverse events in patients with RA treated with TCZ, such as abnormal liver function tests (LFTs) and infections, were more frequent than in comparator groups. This systematic review and meta-analysis suggest that the combination therapy of TCZ with other drugs such as methotrexate and disease-modifying antirheumatic drugs has been studied for various clinical effects concerning safety and clinically significant adverse events. Although the data are promising, long-term performance and safety data need to be fully identified, as well as the risks and benefits of TCZ, especially appropriate timing, dosage, and regimen.

Runx2 silencing promotes adipogenesis via down-regulation of DLK1 in chondrogenic differentiating MSCs.

BACKGROUND: For cartilage regeneration, stem cells are a promising cell source; however, even the advances made in the differentiation of stem cells into precursor-differentiated cartilage cells have not been successful with respect to reprograming these cells to achieve complete differentiation and fully functioning cells until now. Previous findings suggest that Runx2 plays a major role in chondrocyte differentiation and maturation. Although targeting Runx2 has enhanced some chondrocyte properties, the adipogenic lineage shift has eventually occurred in these cells. The present study mainly aimed to reveal the mechanism of this adipogenesis. METHODS: To create inducible artificial shRNA-miR expressing vectors, the designed short hairpin RNAs (shRNAs) were inserted into the pri-mir-30 backbone, cloned into lentiviral pLVET-Tet-on, and transducted into mesenchymal stem cells (MSCs). Runx2 gene was silenced in MSCs either for 1 week or 4 weeks and cultured in the chondrogenic medium. At days 7, 14 and 28, cells were harvested, and chondrogenesis, adipogenesis and hypertrophic states were examined using histochemical staining and a real-time polymerase chain reaction assay. RESULTS: The results showed that the designed shRNA-miR effectively targeted Runx2 in mRNA and protein levels. Chondrogenic markers were up-regulated in constantly silenced Runx2 group; however, adipogenic markers and fat droplets appeared gradually. DLK1 gene was also significantly down-regulated in this group, and overexpression of DLK1 abrogated adipogenesis in the Runx2 targeted group. CONCLUSIONS: Based on these results, it can be concluded that DLK1 is responsible for the lineage shift in Runx2 targeted chondrogenic differentiating MSCs.

The HLA-DRB1*11 group-specific allele is a predictor for alloantibody production in the transfusion-dependent thalassemia patients.

BACKGROUND AND OBJECTIVES: Recently, researchers have shown an increased interest in thalassemia for detecting susceptible factors in alloimmunization development. Alloimmunization, especially against Rh and Kell blood, occurs in 30% of thalassemia dependent transfusion (TDT) patients. The aim of this study is to determine the role of HLA-DRB1*11 and HLA-DRB1*13 group-specific alleles in the production of Rh and Kell alloantibodies. MATERIALS AND METHODS: 106 TDT patients were recruited for this study (54 responders and 52 non-responders). Responder patients developed Rh, Kell and/or specificities alloantibodies. HLA genotyping was done with Sequence-Specific Primers (SSP-PCR) and the results were compared between two groups. RESULTS: A significant association was found between anti-K (P=0.021, OR=2.546, 95%CI) and anti-E (P=0.049, OR=2.304, 95%CI) alloantibodies production with DRB1*11, respectively. Development of Anti-K and Anti-E alloantibodies were associated with DRB1*11 (P = 0.021, OR = 2.546, 95%CI) (P = 0.049, OR = 2.304, 95%CI), respectively. Further analysis showed that DRB1*11 is more frequent in multi responders (responder with both Rh and Kell alloantibodies) than mono-responders, 71% Versus 29%. There was not found any association between the DRB1*13 group-specific allele and the production of alloantibodies (P = 0.584, OR = 0.308, 95%CI). CONCLUSIONS: The evidence from this study suggests that detecting the DRB1*11 group-specific allele before starting transfusion can be useful to identify susceptible patients, increase HSCT transplantation compatibility and blood transfusion management.

The global burden of falls: global, regional and national estimates of morbidity and mortality from the Global Burden of Disease Study 2017.

BACKGROUND: Falls can lead to severe health loss including death. Past research has shown that falls are an important cause of death and disability worldwide. The Global Burden of Disease Study 2017 (GBD 2017) provides a comprehensive assessment of morbidity and mortality from falls. METHODS: Estimates for mortality, years of life lost (YLLs), incidence, prevalence, years lived with disability (YLDs) and disability-adjusted life years (DALYs) were produced for 195 countries and territories from 1990 to 2017 for all ages using the GBD 2017 framework. Distributions of the bodily injury (eg, hip fracture) were estimated using hospital records. RESULTS: Globally, the age-standardised incidence of falls was 2238 (1990-2532) per 100 000 in 2017, representing a decline of 3.7% (7.4 to 0.3) from 1990 to 2017. Age-standardised prevalence was 5186 (4622-5849) per 100 000 in 2017, representing a decline of 6.5% (7.6 to 5.4) from 1990 to 2017. Age-standardised mortality rate was 9.2 (8.5-9.8) per 100 000 which equated to 695 771 (644 927-741 720) deaths in 2017. Globally, falls resulted in 16 688 088 (15 101 897-17 636 830) YLLs, 19 252 699 (13 725 429-26 140 433) YLDs and 35 940 787 (30 185 695-42 903 289) DALYs across all ages. The most common injury sustained by fall victims is fracture of patella, tibia or fibula, or ankle. Globally, age-specific YLD rates increased with age. CONCLUSIONS: This study shows that the burden of falls is substantial. Investing in further research, fall prevention strategies and access to care is critical.

Combined cranberry supplementation and weight loss diet in non-alcoholic fatty liver disease: a double-blind placebo-controlled randomized clinical trial.

A double-blind placebo-controlled randomised clinical trial was conducted on 41 patients with non-alcoholic fatty liver disease (NAFLD). Participants were randomly allocated to receive either a cranberry supplement or a placebo for 12 weeks. Both groups were assigned to follow a weight loss diet. At the end of the study, alanine aminotransferase and insulin decreased significantly in both groups (p < .05); however, this reduction was significantly greater in the cranberry group than in the placebo group (p < .05). Significant improvements in insulin resistance were observed in the cranberry group and between the two groups (p < .001 and p = .020, respectively). Also, there was an improvement in steatosis grade and anthropometric measurements in both groups (p < .05), and there was no significant difference between the two groups in regard to these factors (p > .05). It seems that 288 mg of cranberry extract might improve managing NAFLD, which is equivalent to 26 g of dried cranberry.

Sports Injuries: Diagnosis, Prevention, Stem Cell Therapy, and Medical Sport Strategy.

Sports injuries diagnosis, prevention, and treatment are the most important issues of sports medicine. Fortunately, sports injuries are often treated effectively, and people with damage recover and return to the sport in a satisfactory condition. Meanwhile, many sports injuries and complications can be prevented. In general, sports injuries include acute or chronic injuries. Given increasing in popularity, sports medicine doctors use stem cells to treat a wide variety of sports injuries, including damage to tendons, ligaments, muscles, and cartilage. Stem cell therapy to an injured area could be done through direct surgical application, stem-cell-bearing sutures, and injection. Stem cell therapy holds potential for repair and functional plasticity following sports injuries compared to traditional methods; however, the mechanism of stem cell therapy for sports injuries remains largely unknown. Medical imaging technologies provide the hope to ample the knowledge concerning basic stem cell biology in real time when transplanted into sport-induced damaged organs. Using stem cell treatment might restore continuity and regeneration and promote growth back the organ targets. Besides, using a noninvasive medical imaging method would have the long-time monitoring advantage to the stem cells transplanting individual. The multimodality imaging technique allows for studying acute pathological events following sports injuries; therefore, the use of imaging techniques in medicine permits the straight examination of dynamic regenerative events of specific stem cells following a sports injury in people.

Development and validation of Alzheimer's Disease Animal Model for the Purpose of Regenerative Medicine.

One of the most common age-related neurodegenerative disorders is Alzheimer's disease which globally threatening the health of elderly people. Although there are several pharmacological and non- pharmacological treatments for Alzheimer's disease, they can just decrease the symptoms in these diseases. In this context, cell therapy and regenerative medicine approach as the novel therapeutic strategies for neurodegenerative diseases would be important. Based on scientific research principles, using any novel therapeutic approaches before the run in clinical trials need to take preclinical (animal study) stapes. Accordingly, an animal study can improve our understanding of biological mechanisms of diseases and as an important step should adhering to ethical guidelines and standards. On the other hand, to gain suitable outcomes, it is important to check the appropriate validation of animal models. In this regard, the present review would discuss about the development and validation of appropriate AD animal models in the field of regenerative medicine.

Stem Cell and Obesity: Current State and Future Perspective.

Obesity as a worldwide growing challenge is determined by abnormal fat deposition, which may damage general health. Weight loss and control of related risk factors like type2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, and metabolic syndrome is an important concern in obesity management. Different therapeutic approaches such as lifestyle change, medications, and surgery are introduced for obesity treatment. Despite of gaining partially desirable results, the problem is remained unsolved. Therefore, finding a new approach that can overcome previous limitations is very attractive for both researchers and clinicians. Cell-based therapy using adipose-derived stromal cells seems to be a promising strategy to control obesity and related syndromes. To attain this aim, understanding of different type of adipose tissues, main signaling pathways, and different factors involved in development of adipocyte is essential. Recently, several cell-based methods like stem cell administration, brown adipose tissue transplantation, cell lysates and exosomes have been examined on obese mouse models to manage obesity and related disorders. Successful outcome of such preclinical studies can encourage the cell-based clinical trials in the near future.

Adipose Tissue-Derived Stromal Cells for Wound Healing.

Skin as the outer layer covers the body. Wounds can affect this vital organ negatively and disrupt its functions. Wound healing as a biological process is initiated immediately after an injury. This process consists of three stages: inflammation, proliferation, remodeling. Generally, these three stages occur continuously and timely. However, some factors such as infection, obesity and diabetes mellitus can interfere with these stages and impede the normal healing process which results in chronic wounds. Financial burden on both patients and health care systems, negative biologic effect on the patient's general health status and reduction in quality of life are a number of issues which make chronic wounds as a considerable challenge. During recent years, along with advances in the biomedical sciences, various surgical and non-surgical therapeutic methods have been suggested. All of these suggested treatments have their own advantages and disadvantages. Recently, cell-based therapies and regenerative medicine represent promising approaches to wound healing. Accordingly, several types of mesenchymal stem cells have been used in both preclinical and clinical settings for the treatment of wounds. Adipose-derived stromal cells are a cost-effective source of mesenchymal stem cells in wound management which can be easily harvest from adipose tissues through the less invasive processes with high yield rates. In addition, their ability to secrete multiple cytokines and growth factors, and differentiation into skin cells make them an ideal cell type to use in wound treatment. This is a concise overview on the application of adipose-derived stromal cells in wound healing and their role in the treatment of chronic wounds.

The possible DNA damage induced by environmental organic compounds: The case of Nonylphenol.

Human impact on the environment leads to the release of many pollutants that produce artificial compounds, which can have harmful effects on the body's endocrine system; these are known as endocrine disruptors (EDs). Nonylphenol (NP) is a chemical compound with a nonyl group that is attached to a phenol ring. NP-induced H2AX is a sensitive genotoxic biomarker for detecting possible DNA damage; it also causes male infertility and carcinogenesis. We attempt to comprehensively review all the available evidence about the different ways with descriptive mechanisms for explaining the possible DNA damage that is induced by NP. We systematically searched several databases, including PubMed, Scopus, Web of Science, and gray literature, such as Google Scholar by using medical subheading (MeSH) terms and various combinations of selected keywords from January 1970 to August 2017. The initial search identified 62,737 potentially eligible studies; of these studies, 33 were included according to the established inclusion criteria. Thirty-three selected studies, include the topics of animal model (n = 21), cell line (n = 6), human model (n = 4), microorganisms (n = 1), solid DNA (n = 1), infertility (n = 4), apoptosis (n = 6), and carcinogenesis (n = 3). This review highlighted the possible deleterious effects of NP on DNA damage through the ability to produce ROS/RNS. Finally, it is significant to observe caution at this stage with the continued use of environmental pollutants such as NP, which may induce DNA damage and apoptosis.

Which came first, the risk of migraine or the risk of asthma? A systematic review.

OBJECTIVES: We conducted this review to systematically assess the association and risk of the migraine in the patient with asthma and vice versa. METHODS: We systematically searched publishes articles indexed in PubMed, Scopus, Cochrane library, PsycINFO, CINAHL, ISI Web of Science, Science Direct from inception, and Embase databases until June 2017. The quality assessment of the involved studies was done using the Newcastle-Ottawa Scale (NOS). RESULTS: Eight studies with 389,573 participants were reviewed and selected for data extraction. Among the selected studies, 5 were reported the association between migraine with asthma risk, and the rest three studies reported the risk of asthma in patient with migraine compared to non-moraine individuals. Odds ratio (OR) of migraine for patient with asthma as compared with non-asthmatic individuals was 1.62 (95% CI 1.43-1.82). Data pooling using a random-effect model showed that migraine was associated with a significant increased risk of asthma (relative risk (RR): 1.56; 95% CI: 1.51-1.60; p < .00001). Besides, sub-group and sensitivity analyses supported the positive association between asthma and migraine, and risk of asthma in migraine patients. CONCLUSION: Now it is unknown if control of the asthma will impact the severity of migraines or vice versa, but it is necessary to perform more research to further explain the mechanisms through which asthma increases the frequency of migraine or vice versa. If two conditions linked, once an individual undergo better control of asthma symptoms, might the excruciating migraine ease, too.

Hepatic metastatic niche: from normal to pre-metastatic and metastatic niche.

Liver is the organ responsible for hematopoiesis during fetal life, which is also a target organ of metastasis for several cancers. In order to recognize the hepatic metastatic changes, obtain a better grasp of cancer prevention, treatment, and inhibition mode of hepatic metastasis progression, we investigate the changes and transformation of normal hepatic niche cells to metastatic niche ones in this review. On the other hand, since metastatic diseases alter the liver function, the changes in a number of cancers that metastasize to the liver have also been reviewed. Relevant English-language literature was searched and retrieved from PubMed (1994-2014) using the following keywords: hepatic stem cell niche, hepatic metastatic niche, chemokine, and microRNAs (miRNAs). Also, over 86 published studies were investigated, and bioinformatics analysis of differentially expressed miRNAs in hepatic cancer and metastasis was performed. Metastasis is developed in several stages with specific changes and mechanisms in each stage. Recognition of these changes would lead to detection of new biomarkers and clinical targets involved in specific stages of liver metastasis. Investigation of the hepatic stem cell niche, development of metastasis in liver tissue, as well as changes in chemokines and miRNAs in metastatic hepatic niche can significantly contribute to faster detection of liver metastasis progression.