Construction of immune-related gene pairs signature to predict the overall survival of multiple myeloma patients based on whole bone marrow gene expression profiling.

Multiple myeloma (MM) is a plasma cell dyscrasia that is characterized by the uncontrolled proliferation of malignant PCs in the bone marrow. Due to immunotherapy, attention has returned to the immune system in MM, and it appears necessary to identify biomarkers in this area. In this study, we created a prognostic model for MM using immune-related gene pairs (IRGPs), with the advantage that it is not affected by technical bias. After retrieving microarray data of MM patients, bioinformatics analyses like COX regression and least absolute shrinkage and selection operator (LASSO) were used to construct the signature. Then its prognostic value is assessed via time-dependent receiver operating characteristic (ROC) and the Kaplan-Meier (KM) analysis. We also used XCELL to examine the status of immune cell infiltration among MM patients. 6-IRGP signatures were developed and proved to predict MM prognosis with a P-value of 0.001 in the KM analysis. Moreover, the risk score was significantly associated with clinicopathological characteristics and was an independent prognostic factor. Of note, the combination of age and ß2-microglobulin with risk score could improve the accuracy of determining patients' prognosis with the values of the area under the curve (AUC) of 0.73 in 5 years ROC curves. Our model was also associated with the distribution of immune cells. This novel signature, either alone or in combination with age and ß2-microglobulin, showed a good prognostic predictive value and might be used to guide the management of MM patients in clinical practice.

Immune checkpoint inhibitors in gastrointestinal malignancies: an Umbrella review.

In the Modern era, immune checkpoint inhibitors (ICIs) have been the cornerstone of success in the treatment of several malignancies. Despite remarkable therapeutic advances, complex matrix together with significant molecular and immunological differences have led to conflicting outcomes of ICI therapy in gastrointestinal (GI) cancers. As far we are aware, to date, there has been no study to confirm the robustness of existing data, and this study is the first umbrella review to provide a more comprehensive picture about ICIs' efficacy and safety in GI malignancies. Systematic search on PubMed, Scopus, Web of Science, EMBASE, and Cochrane library identified 14 meta-analyses. The pooled analysis revealed that ICIs application, especially programmed death-1 (PD-1) inhibitors such as Camrelizumab and Sintilimab, could partially improve response rates in patients with GI cancers compared to conventional therapies. However, different GI cancer types did not experience the same efficacy; it seems that hepatocellular carcinoma (HCC) and esophageal cancer (EC) patients are likely better candidates for ICI therapy than GC and CRC patients. Furthermore, application of ICIs in a combined-modal strategy are perceived opportunity in GI cancers. We also assessed the correlation of PD-L1 expression as well as microsatellite status with the extent of the response to ICIs; overall, high expression of PD-L1 in GI cancers is associated with better response to ICIs, however, additional studies are required to precisely elaborate ICI responses with respect to microsatellite status in different GI tumors. Despite encouraging ICI efficacy in some GI cancers, a greater number of serious and fatal adverse events have been observed; further highlighting the fact that ICI therapy in GI cancers is not without cost, and further studies are required to utmost optimization of this approach in GI cancers.

The PI3K/Akt signaling axis and type 2 diabetes mellitus (T2DM): From mechanistic insights into possible therapeutic targets.

Type 2 diabetes mellitus (T2DM) is an immensely debilitating chronic disease that progressively undermines the well-being of various bodily organs and, indeed, most patients succumb to the disease due to post-T2DM complications. Although there is evidence supporting the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway by insulin, which is essential in regulating glucose metabolism and insulin resistance, the significance of this pathway in T2DM has only been explored in a few studies. The current review aims to unravel the mechanisms by which different classes of PI3Ks control the metabolism of glucose; and also to discuss the original data obtained from international research laboratories on this topic. We also summarized the role of the PI3K/Akt signaling axis in target tissues spanning from the skeletal muscle to the adipose tissue and liver. Furthermore, inquiries regarding the impact of disrupting this axis on insulin function and the development of insulin resistance have been addressed. We also provide a general overview of the association of impaired PI3K/Akt signaling pathways in the pathogenesis of the most prevalent diabetes-related complications. The last section provides a special focus on the therapeutic potential of this axis by outlining the latest advances in active compounds that alleviate diabetes via modulation of the PI3K/Akt pathway. Finally, we comment on the future research aspects in which the field of T2DM therapies using PI3K modulators might be developed.

Monkeypox virus diagnosis and laboratory testing.

The multi-country outbreak of monkeypox virus (MPXV) infection, while the coronavirus disease 2019 pandemic is still an ongoing issue, has caused a new challenge. The re-emergence of MPXV and the rising incidence in non-endemic countries is turning into an upcoming threat to global health. Hence, rapid identification of the virus with appropriate methodology with the lowest false results plays a critical role in estimating the global extent of the crisis and providing preventive measures. This review summarised the main applicable strategies for primary detection and confirmation of MPXV and highlighted available data in biosafety, requirements, standard operating procedures, specimen collection, transportation and storage of clinical samples, and waste disposal of the viral agent. Also, various assays including molecular techniques, immunoassays, histopathological methods, electron microscopy, genomic sequencing, and cell culture have been illustrated. Moreover, we reflected on current knowledge of the advantages and disadvantages of each approach.

Inhibition of PI3K/AKT signaling using BKM120 reduced the proliferation and migration potentials of colorectal cancer cells and enhanced cisplatin-induced cytotoxicity.

BACKGROUND: Although extensive efforts have been made to improve the treatment of colorectal cancer (CRC) patients, the prognosis for these patients remains poor. A wide range of anti-cancer agents has been applied to ameliorate the clinical management of CRC patients; however, drug resistance develops in nearly all patients. Based on the prominent role of PI3K/AKT signaling in the development of CRC and current interest in the application of PI3K inhibitors, we aimed to disclose the exact mechanism underlying the efficacy of BKM120, a well-known pan-class I PI3K inhibitor, in CRC-derived SW480 cells. MATERIALS AND METHODS: The effects of BKM120 on SW480 cells were studied using MTT assay, cell cycle assay, Annexin V/PI apoptosis tests, and scratch assay. In the next step, qRT-PCR was used to investigate the underlying molecular mechanisms by which the PI3K inhibitor could suppress the survival of SW480 cells. RESULT: The results of the MTT assay showed that BKM120 could decrease the metabolic activity of SW480 cells in a concentration and time-dependent manner. Investigating the exact mechanism of BKM120 showed that this PI3K inhibitor induces its anti-survival effects through a G2/M cell cycle arrest and apoptosis-mediated cell death. Moreover, the scratch assay demonstrated that PI3K inhibition led to the inhibition of cancer invasion and inhibition of PI3K/AKT signaling remarkably sensitized SW480 cells to Cisplatin. CONCLUSION: Based on our results, inhibition of PI3K/AKT signaling can be a promising approach, either as a single modality or in combination with Cisplatin. However, further clinical studies should be performed to improve our understanding.

Unleashing the potential of gene signatures as prognostic and predictive tools: A step closer to personalized medicine in hepatocellular carcinoma (HCC).

Hepatocellular carcinoma (HCC) is one of the growing malignancies globally, affecting a myriad of people and causing numerous cancer-related deaths. Despite therapeutic improvements in treatment strategies over the past decades, HCC still remains one of the leading causes of person-years of life lost. Numerous studies have been conducted to assess the characteristics of HCC with the aim of predicting its prognosis and responsiveness to treatment. However, the identified biomarkers have shown limited sensitivity, and the translation of these findings into clinical practice has faced challenges. The development of sequencing techniques has facilitated the exploration of a wide range of genes, leading to the emergence of gene signatures. Although several studies assessed differentially expressed genes in normal and HCC tissues to find the unique gene signature with prognostic value, to date, no study has reviewed the task, and to the best of our knowledge, this review represents the first comprehensive analysis of relevant studies in HCC. Most gene signatures focused on immune-related genes, while others investigated genes related to metabolism, autophagy, and apoptosis. Even though no identical gene signatures were found, NDRG1, SPP1, BIRC5, and NR0B1 were the most extensively studied genes with prognostic value. Finally, despite challenges such as the lack of consistent patterns in gene signatures, we believe that comprehensive analysis of pertinent gene signatures will bring us a step closer to personalized medicine in HCC, where treatment strategies can be tailored to individual patients based on their unique molecular profiles.

The PI3K/AKT/mTOR signaling pathway in breast cancer: Review of clinical trials and latest advances.

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of cancer mortality in women. As the phosphatidylinositol 3-kinase (PI3K) signaling pathway is involved in a wide range of physiological functions of cells including growth, proliferation, motility, and angiogenesis, any alteration in this axis could induce oncogenic features; therefore, numerous preclinical and clinical studies assessed agents able to inhibit the components of this pathway in BC patients. To the best of our knowledge, this is the first study that analyzed all the registered clinical trials investigating safety and efficacy of the PI3K/AKT/mTOR axis inhibitors in BC. Of note, we found that the trends of PI3K inhibitors in recent years were superior as compared with the inhibitors of either AKT or mTOR. However, most of the trials entering phase III and IV used mTOR inhibitors (majorly Everolimus) followed by PI3K inhibitors (majorly Alpelisib) leading to the FDA approval of these drugs in the BC context. Despite favorable efficacies, our analysis shows that the majority of trials are utilizing PI3K pathway inhibitors in combination with hormone therapy and chemotherapy; implying monotherapy cannot yield huge clinical benefits, at least partly, due to the activation of compensatory mechanisms. To emphasize the beneficial effects of these inhibitors in combined-modal strategies, we also reviewed recent studies which investigated the conjugation of nanocarriers with PI3K inhibitors to reduce harmful toxicities, increase the local concentration, and improve their efficacies in the context of BC therapy.

Gaillardin exerts potent antileukemic effects on HL-60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment.

The use of all-trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard-risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high-risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus-christi-derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high-risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL-60 cells as a single or combined-form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL-60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL-60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL-60 cells and this study provides new insight into treating APL patients, especially in the high-risk subgroup.

Complement inhibition: A possible therapeutic approach in the fight against Covid-19.

The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has recently been spread to almost all countries around the world. Although most people are immunocompetent to SARS-CoV-2, a small group develops hyper-inflammation that leads to complications like acute respiratory distress syndrome, disseminated intravascular coagulation, and multi-organ failure. Emerging evidence demonstrates that the complement system exerts a crucial role in this inflammatory reaction. Additionally, patients with the severe form of Covid-19 show over-activation of the complement in their skin, sera, and lungs. This study aims to summarise current knowledge concerning the interaction of SARS-CoV-2 with the complement system and to critically appraise complement inhibition as a potential new approach for Covid-19 treatment.

C-Myc inhibition intensified the anti-leukemic properties of Imatinib in chronic myeloid leukemia cells.

BACKGROUND: Due to its remarkable efficacy in producing hematologic, cytogenetic, and molecular remissions, the FDA approved Imatinib as the first-line treatment for newly diagnosed Chronic Myeloid Leukemia (CML) patients. However, in some patients, failure to completely eradicate leukemic cells and the escape of these cells from death will lead to the development of resistance to Imatinib, and many are concerned about the prospects of this Tyrosine Kinase Inhibitor (TKI). It has been documented that the compensatory overexpression of c-Myc is among the most critical mechanisms that promote drug efflux and resistance in CML stem cells. METHODS: In order to examine the potential of c-Myc inhibition through the use of 10058-F4 to enhance the anti-leukemic properties of Imatinib, we conducted trypan blue and MTT assays. Additionally, we employed flow cytometric analysis and qRT-PCR to assess the effects of this combination on cell cycle progression and apoptosis. RESULTS: The findings of our study indicate that the combination of 10058-F4 and Imatinib exhibited significantly stronger anti-survival and anti-proliferative effects on CML-derived-K562 cells in comparison to either agent administered alone. It is noteworthy that these results were also validated in the CML-derived NALM-1 cell line. Molecular analysis of this synergistic effect revealed that the inhibition of c-Myc augmented the efficacy of Imatinib by modulating the expression of genes related to cell cycle, apoptosis, autophagy, and proteasome. CONCLUSIONS: Taken together, the findings of this investigation have demonstrated that the suppression of the c-Myc oncoprotein through the use of 10058-F4 has augmented the effectiveness of Imatinib, suggesting that this amalgamation could offer a fresh perspective on an adjunctive treatment for individuals with CML. Nevertheless, additional scrutiny, encompassing in-vivo examinations and clinical trials, is requisite.

The effects of Abemaciclib on cell cycle and apoptosis regulation in anaplastic thyroid cancer cells.

BACKGROUND: Anaplastic thyroid cancer (ATC) is an aggressive subtype of thyroid cancer, accounting for 1 to 2% of all cases. Deregulations of cell cycle regulatory genes including cyclins, cyclin-dependent kinases (CDKs), and endogenous inhibitors of CDKs (CKIs) are hallmarks of cancer cells and hence, studies indicate the inhibition of CDK4/6 kinases and cell cycle progression as potent therapeutic strategies. In this study, we investigated the anti-tumor activity of Abemaciclib, a CDK4 and CDK6 inhibitor, in ATC cell lines. METHODS AND RESULTS: The ATC cell lines C643 and SW1736 were selected to study the antiproliferative effects of Abemaciclib using a cell proliferation assay and crystal violet staining assay. Annexin V/PI staining and cell cycle analysis by flow cytometry were also performed to examine the effects on apoptosis induction and cell cycle arrest. Wound healing assay and zymography analysis examined the effects of the drug on invasive abilities of ATC cells and Western blot analyses were applied to further study the anti-tumor mechanism of Abemaciclib, in addition to combination treatment with alpelisib. Our data demonstrated that Abemaciclib significantly inhibited cell proliferation and increased cellular apoptosis and cell cycle arrest in ATC cell lines, while considerably reducing cell migration and colony formation. The mechanism seemed to involve the PI3K pathway. CONCLUSION: Our preclinical data highlight CDK4/6 as interesting therapeutic targets in ATC and suggest CDK4/6-blockade therapies as promising strategies in this malignancy.

An overview of extracellular matrix and its remodeling in the development of cancer and metastasis with a glance at therapeutic approaches.

The extracellular matrix (ECM) is an inevitable part of tissues able to provide structural support for cells depending on the purpose of tissues and organs. The dynamic characteristics of ECM let this system fluently interact with the extrinsic triggers and get stiffed, remodeled, and/or degraded ending in maintaining tissue homeostasis. ECM could serve as the platform for cancer progression. The dysregulation of biochemical and biomechanical ECM features might take participate in some pathological conditions such as aging, tissue destruction, fibrosis, and particularly cancer. Tumors can reprogram how ECM remodels by producing factors able to induce protein synthesis, matrix proteinase expression, degradation of the basement membrane, growth signals and proliferation, angiogenesis, and metastasis. Therefore, targeting the ECM components, their secretion, and their interactions with other cells or tumors could be a promising strategy in cancer therapies. The present study initially introduces the physiological functions of ECM and then discusses how tumor-dependent dysregulation of ECM could facilitate cancer progression and ends with reviewing the novel therapeutic strategies regarding ECM.

COVID-19 diagnostic approaches with an extensive focus on computed tomography in accurate diagnosis, prognosis, staging, and follow-up.

Although a long time has passed since its outbreak, there is currently no specific treatment for COVID-19, and it seems that the most appropriate strategy to combat this pandemic is to identify and isolate infected individuals. Various clinical diagnosis methods such as molecular techniques, serologic assays, and imaging techniques have been developed to identify suspected patients. Although reverse transcription-quantitative PCR (RT-qPCR) has emerged as a reference standard method for diagnosis of SARS-CoV-2, the high rate of false-negative results and limited supplies to meet current demand are the main shortcoming of this technique. Based on a comprehensive literature review, imaging techniques, particularly computed tomography (CT), show an acceptable level of sensitivity in the diagnosis and follow-up of COVID-19. Indeed, because lung infection or pneumonia is a common complication of COVID-19, the chest CT scan can be an alternative testing method in the early diagnosis and treatment assessment of the disease. In this review, we summarize all the currently available frontline diagnostic tools for the detection of SARS-CoV-2-infected individuals and highlight the value of chest CT scan in the diagnosis, prognosis, staging, management, and follow-up of infected patients.

Noncoding RNAs in diagnosis and prognosis of graft-versus-host disease (GVHD).

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a functional therapy for a plethora of hematologic malignancies and immune disorders. Graft-versus-host disease (GVHD), on the other hand, is one of the major complications ahead of a successful HSCT, contributing to transplant-associated morbidity and mortality. Notably, little is known about the underlying mechanism of this event; therefore, exploring precise biomarkers and uncovering the molecular pathogenesis of GVHD is valuable for early diagnosis and treatment optimization. Thanks to the advances in sequencing techniques, the noncoding sequences of the human genome-formerly considered "junk"-are now identified as functional molecules. Noncoding RNAs (ncRNA) control cellular responses by regulating gene expression, and previous studies have shown that these tiny molecules, especially microRNAs (miRNAs), can affect allogeneic T cell responses in both animal models and clinical experiments. The present study gives an overview of the functions of various miRNAs in regulating T cell responses in GVHD. We also provide an outlook on miRNAs and long noncoding RNAs (lncRNAs) potential role in GVHD with the hope of providing a future research direction for expanding their application as the sensitive and noninvasive diagnostic or prognostic biomarkers and also the promising therapeutic targets for improving outcomes after allogeneic HSCT.

Resistance to immunotherapy in human malignancies: Mechanisms, research progresses, challenges, and opportunities.

Despite remarkable advances in different types of cancer therapies, an effective therapeutic strategy is still a major and significant challenge. One of the most promising approaches in this regard is immunotherapy, which takes advantage of the patients' immune system; however, the many mechanisms that cancerous cells harbor to extend their survival make it impossible to gain perfect eradication of tumors. The response rate to cancer immunotherapies, especially checkpoint inhibitors and adoptive T cell therapy, substantially differs in various cancer types with the highest rates in advanced melanoma and non-small cell lung cancer. Indeed, the lack of response in many tumors indicates primary resistance that can originate from either tumor cells (intrinsic) or tumor microenvironment (extrinsic). On the other hand, some tumors show an initial response to immunotherapy followed by relapse in few months (acquired resistance). Understanding the underlying molecular mechanisms of immunotherapy resistance makes it possible to develop effective strategies to overcome this hurdle and boost therapy outcomes. In this review, we take a look at immunotherapy strategies and go through a number of primary and acquired resistance mechanisms. Also, we present various ongoing methods to overcoming resistance and introduce some promising fields to improve the outcome of immunotherapy in patients affected with cancer.

The PI3K/Akt/mTOR axis in colorectal cancer: Oncogenic alterations, non-coding RNAs, therapeutic opportunities, and the emerging role of nanoparticles.

Colorectal cancer (CRC) is one of the deadliest human malignancies worldwide. Several molecular pathways have been demonstrated to be involved in the initiation and development of CRC which among them, the overactivation of the phosphatidyl-inositol 3-kinase (PI3K)/Akt/mTOR axis is of importance. The current review aims to unravel the mechanisms by which the PI3K/Akt/mTOR pathway affects CRC progression; and also, to summarize the original data obtained from international research laboratories on the oncogenic alterations and polymorphisms affecting this pathway in CRC. Besides, we provide a special focus on the regulatory role of noncoding RNAs targeting the PI3K/Akt/mTOR pathway in this malignancy. Questions on how this axis is involved in the inhibition of apoptosis, in the induction of drug resistance, and the angiogenesis, epithelial to mesenchymal transition, and metastasis are also responded. We also discussed the PI3K/Akt pathway-associated prognostic and predictive biomarkers in CRC. In addition, we provide a general overview of PI3K/Akt/mTOR pathway inhibition whether by chemical-based drugs or by natural-based medications in the context of CRC, either as monotherapy or in combination with other therapeutic agents; however, those treatments might have life-threatening side effects and toxicities. To the best of our knowledge, the current review is one of the first ones highlighting the emerging roles of nanotechnology to overcome challenges related to CRC therapy in the hope that providing a promising platform for the treatment of CRC.

Synergistic effects of BKM120 and panobinostat on pre-B acute lymphoblastic cells: an emerging perspective for the simultaneous inhibition of PI3K and HDACs.

The reputation of conventional treatment in acute lymphoblastic leukemia (ALL) has recently been questioned due to the considerable increment in the number of relapsed patients. The remarkable role of histone deacetylase (HDAC) enzymes in induction of chemo-resistance has provided an opportunity for HDAC inhibitors to be used as a treatment strategy in ALL; however, the compensatory activation of oncogenic pathways may negatively affect their promising effects. In the present study, we found an attenuating effect for PI3K axis on the anti-leukemic effects of panobinostat in pre-B ALL-derived Nalm-6 cells, as the harnessing of this pathway using BKM120 or CAL-101 resulted in a significant reduction in the number of viable cells as well as the metabolic activity. Moreover, we found the altered expression of p21, p27, c-Myc, and CDK4 upon co-treatment of the cells with panobinostat and BKM120, which was associated with a substantial blockage of cell cycle progression at G2/M phase. The companionship of the PI3K inhibitor with HDAC inhibitor also potentiated panobinostat-induced apoptotic cell death and enhanced the mRNA of Foxo3a and Foxo4. Conclusively, this study sheds light on the adjuvantive effects of BKM120 on panobinostat efficacy and outlined that the simultaneous inhibition of PI3K and HDACs may be a promising therapeutic approach to improve the cure rates of ALL.

Synergistic apoptotic effect of Mcl-1 inhibition and doxorubicin on B-cell precursor acute lymphoblastic leukemia cells.

BACKGROUND: Myeloid cell leukemia-1 (MCL-1) is a component of the Bcl-2 anti-apoptotic family that plays a key role in cell proliferation and differentiation. Despite tremendous improvements toward identification of the role of MCL-1 in leukemia progression, the functional significance and molecular mechanism behind the effect of MCL-1 overexpression on the proliferation of B-cell precursor acute lymphoblastic leukemia (BCP-ALL) has not been clarified. In addition, less well appreciated is the effect of MCL-1 inhibition on the potentiation of doxorubicin-induced apoptosis in BCP-ALL cell lines. In the present study, we aimed to shed light on the anti-cancer properties of S63845, a potent Mcl-1 inhibitor, in BCP-ALL cell lines either alone or in combination with a chemotherapeutic drug. METHODS AND RESULTS: Mononuclear cells from patients with Pre-B ALL and BCP-ALL cell lines were treated with S63845 in presence or absence of doxorubicin, induction of apoptosis was evaluated using Annexin-V/PI staining kit. mRNA and protein expression levels were assessed by qRT-PCR and western blot analysis, respectively. Our results declared that inhibition of Mcl-1 impairs cell growth and induces apoptosis in pre-B ALL cells through activation of caspase-3 and up-regulation of a repertoire of pro-apoptotic Bcl-2 family. Additionally, S63845 acts synergically with doxorubicin to induce apoptosis in BCP-ALL cell lines. CONCLUSIONS: Our data declared that MCL-1 inhibition alone or in combination with a chemotherapeutic agent is considered an appealing strategy for the induction of apoptosis in BCP-ALL cells.

An overview of long noncoding RNAs: Biology, functions, therapeutics, analysis methods, and bioinformatics tools.

Long noncoding RNAs (lncRNAs) are a diverse class of RNAs whose functions are widespread in all branches of life and have been the focus of attention in the last decade. While a huge number of lncRNAs have been identified, there is still much work to be done and plenty to be learned. In the current review, we begin with the biogenesis and function of lncRNAs as they are involved in the different cellular processes from regulating the architecture of chromosomes to controlling translation and post-translation modifications. Questions on how overexpression, mutations, or deficiency of lncRNAs can affect the cellular status and result in the pathogenesis of various human diseases are responded to. Besides, we allocate an overview of several studies, concerning the application of lncRNAs either as diagnostic and prognostic biomarkers or novel therapeutics. We also introduce the currently available techniques to explore details of lncRNAs such as their function, cellular localization, and structure. In the last section, as exponentially growing data in this area need to be gathered and organized in comprehensive databases, we have a particular focus on presenting general and specialized databases. Taken together, with this review, we aim to provide the latest information on different aspects of lncRNAs to highlight their importance in physiopathologic states and take a step towards helping future studies.

Toll-like receptors (TLRs): An old family of immune receptors with a new face in cancer pathogenesis.

In the dark path of tumorigenesis, the more carefully the cancer biology is studied, the more brilliant answers could be given to the countless questions about its orchestrating derivers. The identification of the correlation between Toll-like receptors (TLRs) and different processes involved in carcinogenesis was one of the single points of blinding light highlighting the interconnection between the immune system and cancer. TLRs are a wide family of single-pass membrane-spanning receptors that have developed through the evolution to recognize the structurally conserved molecules derived from microorganisms or damaged cells. But this is not everything about these receptors as they could orchestrate several downstream signalling pathways leading to the formation or suppression of cancer cells. The present review is tempted to provide a concise schematic about the biology and the characters of TLRs and also summarize the major findings of the regulatory role of TLRs and their associated signalling in the pathogenesis of human cancers.