Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets.

Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.

Baseline Gastric Volume in Fasting Diabetic Patients Is Not Higher than That in Nondiabetic Patients: A Cross-sectional Noninferiority Study.

BACKGROUND: The physiology of diabetes mellitus can increase the risk of perioperative aspiration, but there is limited and contradictory evidence on the incidence of "full stomach" in fasting diabetic patients. The aim of this study is to assess the baseline gastric content (using gastric ultrasound) in diabetic and nondiabetic patients scheduled for elective surgery who have followed standard preoperative fasting instructions. METHODS: This was a prospective, noninferiority study of 180 patients (84 diabetic and 96 nondiabetic patients). Bedside ultrasound was used for qualitative and quantitative assessment of the gastric antrum in the supine and right lateral decubitus positions. Fasting gastric volume was estimated based on the cross-sectional area of the gastric antrum and a validated model. The hypothesis was that diabetic patients would not have a higher baseline fasting gastric volume compared to nondiabetic patients, with a noninferiority margin of 0.4 ml/kg. Secondary aims included the comparison of the incidence of full stomach (solid content or more than 1.5 mL/kg of clear fluid), estimation of the 95th percentile of the gastric volume distribution in both groups, and examination of the association between gastric volume, glycemic control, and diabetic comorbidities. RESULTS: The baseline gastric volume was not higher in diabetic patients (0.81 ± 0.61 ml/kg) compared to nondiabetic patients (0.87 ± 0.53 ml/kg) with a mean difference of -0.07 ml/kg (95% CI, -0.24 to 0.10 ml/kg). A total of 13 (15.5%) diabetic and 11 (11.5%) nondiabetic patients presented more than 1.5 ml/kg of gastric volume (95% CI for difference, -7.1 to 15.2%). There was little correlation between the gastric volume and either the time since diagnosis or HbA1C. CONCLUSIONS: The data suggest that the baseline gastric volume in diabetic patients who have followed standard fasting instructions is not higher than that in nondiabetic patients.

Exosomal non-coding RNAs: Blueprint in colorectal cancer metastasis and therapeutic targets.

Colorectal cancer (CRC) is ranked as the world's third-most prevalent cancer, and metastatic CRC considerably increases cancer-related fatalities globally. A number of complex mechanisms that are strictly controlled at the molecular level are involved in metastasis, which is the primary reason for death in people with CRC. Recently, it has become clear that exosomes, which are small extracellular vesicles released by non-tumorous and tumorigenic cells, play a critical role as communication mediators among tumor microenvironment (TME). To facilitate communication between the TME and cancer cells, non-coding RNAs (ncRNAs) play a crucial role and are recognized as potent regulators of gene expression and cellular processes, such as metastasis and drug resistance. NcRNAs are now recognized as potent regulators of gene expression and many hallmarks of cancer, including metastasis. Exosomal ncRNAs, like miRNAs, circRNAs, and lncRNAs, have been demonstrated to influence a number of cellular mechanisms that contribute to CRC metastasis. However, the molecular mechanisms that link exosomal ncRNAs with CRC metastasis are not well understood. This review highlights the essential roles that exosomal ncRNAs play in the progression of CRC metastatic disease and explores the therapeutic choices that are open to patients who have CRC metastases. However, exosomal ncRNA treatment strategy development is still in its early phases; consequently, additional investigation is required to improve delivery methods and find novel therapeutic targets as well as confirm the effectiveness and safety of these therapies in preclinical and clinical contexts.

A review on the role of mir-16-5p in the carcinogenesis.

miR-16-5p is microRNA with important roles in the development of diverse malignancies including neuroblastoma, osteosarcoma, hepatocellular carcinoma, cervical cancer, breast cancer, brain tumors, gastrointestinal cancers, lung cancer and bladder cancer. This miRNA has 22 nucleotides. hsa-miR-16-5p is produced by MIR16-1 gene. First evidence for its participation in the carcinogenesis has been obtained by studies reporting deletion and/or down-regulation of these miRNAs in chronic lymphocytic leukemia. Subsequent studies have shown down-regulation of miR-16-5p in a variety of cancer cell lines and clinical samples. Besides, tumor suppressor role of miR-16-5p has been verified in animal models of different types of cancers. Studies in these models have shown that over-expression of this miRNA or modulation of expression of lncRNAs that sponge this miRNA can block carcinogenic processes. In the current review, we summarize function of miR-16-5p in the development and progression of different cancers.

Functional interplay between long non-coding RNAs and Breast CSCs.

Breast cancer (BC) represents aggressive cancer affecting most women's lives globally. Metastasis and recurrence are the two most common factors in a breast cancer patient's poor prognosis. Cancer stem cells (CSCs) are tumor cells that are able to self-renew and differentiate, which is a significant factor in metastasis and recurrence of cancer. Long non-coding RNAs (lncRNAs) describe a group of RNAs that are longer than 200 nucleotides and do not have the ability to code for proteins. Some of these lncRNAs can be mainly produced in various tissues and tumor forms. In the development and spread of malignancies, lncRNAs have a significant role in influencing multiple signaling pathways positively or negatively, making them promise useful diagnostic and prognostic markers in treating the disease and guiding clinical therapy. However, it is not well known how the interaction of lncRNAs with CSCs will affect cancer development and progression.Here, in this review, we attempt to summarize recent findings that focus on lncRNAs affect cancer stem cell self-renewal and differentiation in breast cancer development and progression, as well as the strategies and challenges for overcoming lncRNA's therapeutic resistance.

The Emerging Roles of the ß-Secretase BACE1 and the Long Non-coding RNA BACE1-AS in Human Diseases: A Focus on Neurodegenerative Diseases and Cancer.

The ß-Secretase (BACE1) is widely studied to be particularly involved in amyloid deposition, a process known as the pathogenic pathway in neurodegenerative diseases. Therefore, BACE1 expression is frequently reported to be upregulated in brain samples of the patients with Alzheimer's disease (AD). BACE1 expression is regulated by BACE1-AS, a long non-coding RNA (lncRNA), which is transcribed in the opposite direction to its locus. BACE1-AS positively regulates the BACE1 expression, and their expression levels are regulated in physiological processes, such as brain and vascular homeostasis, although their roles in the regulation of amyloidogenic process have been studied further. BACE1-AS dysregulation is reported consistent with BACE1 in a number of human diseases, such as AD, Parkinson's disease (PD), heart failure (HF), and mild cognitive impairment. BACE1 or less BACE1-AS inhibition has shown therapeutic potentials particularly in decreasing manifestations of amyloid-linked neurodegenerative diseases. Here, we have reviewed the role of lncRNA BACE1 and BACE1-AS in a number of human diseases focusing on neurodegenerative disorders, particularly, AD.

Adolescent girls' recommendations for the design of a human papillomavirus vaccination program in Sindh, Pakistan: a qualitative study.

PURPOSE: Vaccination of adolescent girls against human papillomavirus (HPV) significantly reduces the incidence of cervical cancer. HPV vaccines are available in Pakistan but plans to develop HPV vaccination program are at a nascent stage. We conducted a formative study to explore adolescent girls' knowledge and perspectives on HPV and cervical cancer and collect their recommendations for implementing an HPV vaccination program in their community. METHODS: Using qualitative exploratory study design, we conducted four focus group discussions (FGDs) with 12 adolescent girls per group in District West, Karachi. We recruited unmarried girls aged 16-19 years from schools and community settings between May-December 2020. Data analysis was done using NVivo. RESULTS: Overall, participants displayed a positive attitude toward HPV vaccine. However, they were unfamiliar with basic concepts related to female reproductive health. Female relatives were indicated as girls' preferred point of contact for discussions on HPV and cervical cancer, but fathers were portrayed as decision-making authority on vaccination. Participants indicated vaccine hesitancy among parents may affect HPV vaccination uptake. Girls suggested individual household visits and community-based camps as strategies for successful implementation of HPV vaccination program. A solid foundation of trust between girls' families, program managers, and other stakeholders emerged as a key asset for the program's success. CONCLUSION: Adolescent girls' suggestions of informing key decision-makers in the family (particularly fathers) of the benefits of HPV vaccination, establishing trust with vaccine providers, and increasing accessibility of vaccinations should be explored for successful implementation of an HPV vaccination program in Pakistan.

Signaling pathways modulated by miRNAs in breast cancer angiogenesis and new therapeutics.

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors by suppressing the expression of target genes, some of which are engaged in angiogenic signaling pathways directly or indirectly. Tumor development and metastasis are dependent on angiogenesis, and it is the main reason for the poor prognosis of cancer patients. New blood vessels are formed from pre-existing vessels when angiogenesis occurs. Thus, it is essential to develop primary tumors and the spread of cancer to surrounding tissues. MicroRNAs (miRNAs) are small noncoding RNAs involved in various biological processes. They can bind to the 3'-UTR of their target genes and prevent them from expressing. MiRNAs control the activity of endothelial cells (ECs) through altering many biological pathways, which plays a key role in cancer progression and angiogenesis. Recent findings revealed that tumor-derived extracellular vesicles participated directly in the control of tumor angiogenesis by delivering miRNAs to ECs. miRNAs recently show great promise in cancer therapies to inhibit angiogenesis. In this study, we showed the miRNA-regulated signaling pathways in tumor angiogenesis with highlighting the anti-angiogenic therapy response and miRNA delivery methods that have been used to inhibit angiogenesis in both in vivo and in vitro studies.

The emerging roles of NGS in clinical oncology and personalized medicine.

Next-generation sequencing (NGS) has been increasingly popular in genomics studies over the last decade, as new sequencing technology has been created and improved. Recently, NGS started to be used in clinical oncology to improve cancer therapy through diverse modalities ranging from finding novel and rare cancer mutations, discovering cancer mutation carriers to reaching specific therapeutic approaches known as personalized medicine (PM). PM has the potential to minimize medical expenses by shifting the current traditional medical approach of treating cancer and other diseases to an individualized preventive and predictive approach. Currently, NGS can speed up in the early diagnosis of diseases and discover pharmacogenetic markers that help in personalizing therapies. Despite the tremendous growth in our understanding of genetics, NGS holds the added advantage of providing more comprehensive picture of cancer landscape and uncovering cancer development pathways. In this review, we provided a complete overview of potential NGS applications in scientific and clinical oncology, with a particular emphasis on pharmacogenomics in the direction of precision medicine treatment options.

MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets.

The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. There's increasing evidence showed that various miRNAs play a significant role in disease processes; specifically, they are observed and over-expressed in a wide range of diseases linked to the angiogenesis process. However, more studies are required to reach the best findings and identify the link among miRNA expression, angiogenic pathways, and immune response-related genes to find new therapeutic targets. Here, we summarized the recent updates on miRNA signatures and their cellular targets in the development of breast tumor angiogenetic and discussed the strategies associated with miRNA-based therapeutic targets as anti-angiogenic response.

Exploring Obstetrical Interventions and Stratified Cesarean Section Rates Using the Robson Classification in Tertiary Care Hospitals in the United Arab Emirates.

OBJECTIVE: The objective of the present study was to explore obstetric management in relation to clinical, maternal and child health outcomes by using the Robson classification system. METHODS: Data was collected from obstetrics registries in tertiary care hospitals in Dubai, United Arab Emirates (UAE). RESULTS: The analysis of > 5,400 deliveries (60% of all the deliveries in 2016) in major maternity hospitals in Dubai showed that groups 5, 8 and 9 of Robson's classification were the largest contributors to the overall cesarean section (CS) rate and accounted for 30% of the total CS rate. The results indicate that labor was spontaneous in 2,221 (45%) of the women and was augmented or induced in almost 1,634 cases (33%). The birth indication rate was of 64% for normal vaginal delivery, of 24% for emergency CS, and of 9% for elective CS. The rate of vaginal birth after cesarean was 261 (6%), the rate of external cephalic version was 28 (0.7%), and the rate of induction was 1,168 (21.4%). The prevalence of the overall Cesarean section was 33%; with majority (53.5%) of it being repeated Cesarean section. CONCLUSION: The CS rate in the United Arab Emirates (UAE) is higher than the global average rate and than the average rate in Asia, which highlights the need for more education of pregnant women and of their physicians in order to promote vaginal birth. A proper planning is needed to reduce the number of CSs in nulliparous women in order to prevent repeated CSs in the future. Monitoring both CS rates and outcomes is essential to ensure that policies, practices, and actions for the optimization of the utilization of CS lead to improved maternal and infant outcomes.

Exploring obstetrical interventions and stratified cesarean section rates using the Robson classification in tertiary Care hospitals in the united arab emirates

Abstract Objective The objective of the present study was to explore obstetric management in relation to clinical, maternal and child health outcomes by using the Robson classification system. Methods Data was collected from obstetrics registries in tertiary care hospitals in Dubai, United Arab Emirates (UAE). Results The analysis of > 5,400 deliveries (60% of all the deliveries in 2016) in major maternity hospitals in Dubai showed that groups 5, 8 and 9 of Robson's classification were the largest contributors to the overall cesarean section (CS) rate and accounted for 30% of the total CS rate. The results indicate that labor was spontaneous in 2,221 (45%) of the women and was augmented or induced in almost 1,634 cases (33%). The birth indication rate was of 64% for normal vaginal delivery, of 24% for emergency CS, and of 9% for elective CS.The rate of vaginal birth after cesarean was 261(6%), the rate of external cephalic version was 28 (0.7%), and the rate of induction was 1,168 (21.4%). The prevalence of the overall Cesarean section was 33%; with majority (53.5%) of it being repeated Cesarean section. Conclusion The CS rate in the United Arab Emirates (UAE) is higher than the global average rate and than the average rate in Asia, which highlights the need for more education of pregnant women and of their physicians in order to promote vaginal birth. A proper planning is needed to reduce the number of CSs in nulliparous women in order to prevent repeated CSs in the future. Monitoring both CS rates and outcomes is essential to ensure that policies, practices, and actions for the optimization of the utilization of CS lead to improved maternal and infant outcomes.

Assessment of elastosis in invasive ductal carcinoma of the breast compared to fibroadenoma among Sudanese patients using conventional histochemical methods.

We aimed to identify, using histochemical methods, the degree of elastosis in a malignant breast tumor compared to a benign tumor. Sixty-four tissue blocks were used in this study of which 34 (53.1%) were Invasive ductal carcinoma (IDC) (cases) and 30 (46.8%) were fibroadenomas (controls). Examination of Verhoeff's stained sections revealed different grades of elastosis in 29 (85.2%) cases compared to seven (23.3%) in controls. These findings indicated that elastosis was a prominent feature of IDC (p < 0.000). IDC was associated with more frequent occurrence of different grades of elastosis and should, therefore, be considered a valuable histological finding. Nevertheless, more advanced technology for quantitative measurements of the staining density is recommended to confirm this variation.