Current Molecular Medicine - Volume 21, Issue 5, 2021

Gastric cancer (GC) has been found to be the second leading cause of cancer-associated deaths in the world, and is usually detected in the advanced stages. It has been shown that surgery is the major therapeutic approach in the treatment of subjects with GC. Hence, early and fast diagnosis of this malignancy is very important for good subject outcomes. Non-invasive diagnostic platforms, including evolutionary endoscopy and positron emission tomography (PET), are employed for the diagnosis of subjects with GC. Along with imaging techniques, the utilization of biomarkers has emerged as a new diagnosis option for early and fast detection of GC. Multiple lines of evidence have revealed a variety of biomarkers, including microRNAs, exosomes, circulating tumor cells, circular RNAs, cell free DNAs, and various proteins, which could be used as diagnostic biomarkers in patients with GC. Taken together, these findings suggest that the joint application of imaging techniques and different biomarkers could be introduced as a new detection approach in the treatment and screening response to therapy in the subjects with GC. Herein, we have summarized various imaging techniques and biomarkers as powerful tools in the detection of GC.

Premature ovarian failure (POF) refers to ovarian dysfunction in women under 40 years old. It is characterized by low estrogen, high gonadotropin, amenorrhea, and infertility, which seriously affect physical and mental health of women. The pathogenic factors of POF include iatrogenic factors, autoimmune factors, genetic factors, oxidative stress, infection, thyroid dysfunction, and adrenal diseases. Chemotherapy is a common cause of POF and is gaining increasing attention. With the development of modern medicine and advances in understanding cancer, women’s cancer survival rates have been significantly increased. Currently, the main treatment options for POF are hormone supplement and in vitro activation (IVA), but there is still no specific treatment for POF. Stem cells, known as undifferentiated cells of multicellular organisms, exhibit characteristics of self-renewal, directional differentiation into different cells, and low immunogenicity. Thus, they have potential in regenerative medicine and provide a promising direction for POF treatment. In this review, we summarize the latest research progress of various stem cells in chemotherapy-induced POF models to provide a theoretical basis for further research and treatment.

COVID-19 is an emerging disease that is a major threat to the global community. The main challenge in this disease is the lack of proper or proven medication. The drugs used to treat this disease are only for symptomatic treatment. Studies of other coronaviruses, such as SARS and MERS, suggest that quercetin has sufficient potential to treat COVID-19. Previous studies have shown that quercetin reduces the entry of the virus into the cell by blocking the ACE2 receptor, as well as reducing the level of interleukin-6 in SARS and MERS patients. Therefore, the aim of this review was to scrutinize the potential of quercetin as a drug in the treatment of COVID-19 from a molecular perspective.

Dexamethasone (Dex) is a synthetic corticosteroid hormone derived from the steroid chemical group and is applicable in treating several pathological conditions like inflammation, autoimmune disease, and malignancies. Recent investigations on the mechanism of action of Dex and its possible interactions with other cellular regulatory networks may help explain the inconsistent effects of Dex in cancer treatment. Finetuning regulation of essential post-transcriptional regulators such as microRNA (miRNAs) has indispensable impacts on modulating fundamental cellular processes, including gene expression, cell proliferation, cell cycling, and apoptosis. Dex appears to act as a double-edged sword on cancer cell progression and metastasis through regulating miRNA networks. As a proof of concept, recent investigations have proved Dex to be effective in treatment of cancer either individually or in combination with other therapeutical compounds, while several evidences have point to the controversial effects of Dex in the promotion of cancer cell survival, drug-resistance, and metastasis. In addition, it has been proven that other non-coding RNAs (ncRNAs) can also be directly or indirectly affected by Dex. In this review, we aimed to investigate the controversial effect of Dex on the cancer-related miRNAs.

Cervical cancer, cancer arising from the uterine cervix, has been regarded as the fourth most frequent gynecological malignancy among females worldwide. Epidemiological reports have shown that uterine cervical cancer is a global health issue among women of especially developing countries and consequently creates an economic and medical burden in the society. The main causative agent of cervical carcinoma is high-risk human papilloma virus (HPV 16 and HPV 18). Molecular studies have revealed the expression of two viral genes E6 and E7, after HPV infection in the epithelial cells of the cervix. These gene products are known to inactivate the major tumor suppressors, p53 and retinoblastoma protein (pRB), respectively. Moreover, the role of self-renewal pathways, such as Hedgehog, Notch, and Wnt, has also been linked with drug resistance in cancer cells and epithelial mesenchymal transition during metastasis in the pathogenesis of cervical cancer. Although the mechanism of interaction of HPV E6 and E7 with each and every component of the above described developmental pathways is not elucidated yet, preliminary reports of their cross-talk have begun to emerge. Understanding the interplay between these oncoproteins and developmental/self-renewal pathways is highly important in terms of designing new and targeted therapeutic approaches against cervical cancer. Hence, this review cynosure the carcinogenesis of HPV with a brief description of its virology and also establishes the cross-talk between oncoproteins E6 and E7 and Hedgehog, Notch, and Wnt signaling pathway.

Janus kinase-2 (JAK2) is a non-receptor tyrosine kinase that serves key roles as the intracellular signaling effector of the cytokine receptor, such as mediating effects of leptin, erythropoietin, interferon, and growth hormone. A lot of molecular underlying mechanisms of JAK2 participation are known, however, additional signaling mechanisms of its activation, regulation, and pleiotropic signaling roles are still being explored. Here, we review the current knowledge of JAK2-mediated cellular signaling at the molecular level. In the beginning, we will focus on the recent advances in JAK2 activation and regulation. A part of our review focuses on the JAK2 involvement in various diseases/conditions. Recent advances highlight the molecular regulatory mechanisms utilized by the JAK2 signaling, thus, enabling to consider alternative therapeutic strategies to treat various diseases/conditions mediated by JAK2 by using it as a therapeutic target.

Myeloid cell leukemia 1 (Mcl-1) is a member of the Bcl-2 family of proteins with anti-apoptotic activity. It plays a key role in the regulation of the intrinsic pathway of apoptosis. Moreover, Mcl-1 is correlated with the progression and drug-resistance of various cancers. The development of inhibitors of Mcl-1 may provide effective cancer therapies. While the inhibitors of other Bcl-2 anti-apoptotic proteins have been well explored, the discovery of Mcl-1inhibitors with high selectivity has been challenging. In this review, we summarize the recent literature on small molecule and peptide inhibitors of Mcl-1, which are divided into different types including peptide inhibitors, gossypol derivatives, marinopyrrole derivatives, S1 derivatives, indole derivatives, quinoline derivatives, S63845, AZD5991, AMG176, etc. Their biological activities are also summarized. Mcl-1 is a valid drug target and inhibition of Mcl-1 with a small molecule inhibitor is a promising strategy for cancer therapy.