Eucalyptus Essential Oil Based Nanoemulsions: Preparation and Biological Activities.

Eucalyptus essential oil has remarkable industrial importance and biological properties due to its effectiveness against various diseases, reported throughout human history. Despite the extraordinary bioactivities of essential oil, its applications are limited due to volatility, insolubility in water, and less stability. Formulation of nanoemulsion is the best way to enhance the bio-efficacy of this essential oil and eliminate the factors responsible for limited application. This review article compiles the information regarding formulation of Eucalyptus essential oil-based nanoemulsion and their several biological activities and medicinal properties including antibacterial, antifungal, larvicidal, insecticidal, and cytotoxic activities etc. The bio-efficacy of essential oil-based nanoemulsion has also been found to be enhanced as compared utilization of essential oil alone. This review can be beneficial for researchers working on medicinal plant-based natural products, specifically containing Eucalyptus essential oil, to explore new research horizons in this emerging field.

Association of Oral Submucous Fibrosis Risk with GSTM1 and GSTT1 Gene Polymorphisms.

OBJECTIVE: To determine the association of GSTM1 and GSTT1 polymorphisms with oral submucous fibrosis (OSF). STUDY DESIGN: A case-control study. Place and Duration of the Study: Department of Human Genetics and Molecular Biology, University of Health Sciences, Lahore and Oral and Maxillofacial Surgery Department, de Montmorency, College of Dentistry/ Punjab Dental Hospital, Lahore, Pakistan, from 1st April 2019 to 31st April 2020. METHODOLOGY: OSF patients were diagnosed with different clinical staging of mouth opening by Vernier caliper with the help of a professional dentist in the Department of Oral and Maxillofacial, de Montmorency, College of Dentistry, Lahore. One hundred and eight blood samples of OSF patients and 108 samples of normal controls were collected. Genomic DNA was obtained from whole-blood extraction. Multiplex PCR amplification using GSTM1, GSTT1, and ß -Globin gene primers was performed. RESULTS: GSTM1 and GSTT1 null genotypes frequencies were found in 43.5% (47/108) and 13.9% (15/108) of controls, whereas 54.6% (59/108) and 25.9% (28/108) of OSF patients, respectively. OSF patients had a greater frequency rate of GSTM1 and GSTT1 null genotypes than controls [OR 1.56, 95% CI 0.91-2.67 (p=0.13)] and [OR 2.17, 95% CI 1.08-4.34 (p=0.04)], respectively. The GSTT1 genotype was found statistically significant with OSF (p=0.05), and risk was also determined. The cumulative effect of null genotypes of GSTM1/GSTT1 did not show any association with the controls and in OSF patients. Proportions of active and null alleles of the patient group were; 86.1%/13.9%; and in control, it was 92.6%/7.4% (OR = 2.01; CI: 0.82-4.97; p=0.18), respectively. CONCLUSION: The study determined a statistically significant association of GSTT1 gene polymorphism with OSF. KEY WORDS: Oral submucous fibrosis, GSTM1, GSTT1, Gene polymorphisms, Genetic risk.

Healthcare and economic burden of heart failure with amyloidosis: An insight from National Readmission Database.

INTRODUCTION: We analyzed trends, causes and predictors of 30-days readmission in cardiac amyloidosis and inspected the impact of these readmissions on mortality, morbidity, and utilization of healthcare resources. METHODS: Heart Failure with cardiac amyloidosis patients were selected from National readmission Database (NRD) using ICD-10 CM codes. Patients younger than 18 years, elective readmissions, readmissions due to trauma, patients with missing data and December 2018 admissions were excluded. Primary outcome was all-cause 30-day readmissions rate, secondary outcomes were factors associated with 30-days readmissions and their effect on morbidity, mortality, and healthcare resource utilization. RESULTS: Out of 4123 total heart failure with cardiac amyloidosis index admissions in 2018, 3374 patients were included in final analysis. 19.6% were readmitted within 30 days. Readmitted patients were younger, sicker, admitted to small or large hospital. Hypertensive heart and Chronic Kidney Disease (CKD Stage I-IV) with Congestive Heart Failure (CHF), hypertensive heart and CKD (Stage V) or End Stage Renal Disease (ESRD) with CHF, hypertensive heart disease with CHF, acute kidney failure, and sepsis were the most common causes of readmissions. Young age, admission to small and large size hospitals were independent predictors of 30-day readmissions. Readmissions had higher mortality, costed 6.6 extra in hospital days to patients and $16380 per admission to healthcare system. CONCLUSIONS: Cardiac amyloidosis readmissions were associated with increased morbidity and mortality of patients and extra burden on the healthcare system. There is a need to identify patients at risk for readmissions to improve patient outcomes and decrease healthcare cost.

Atrial Myxoma: An Unusual Etiology of Ischemic Stroke in an Adult Patient.

Atrial myxoma is the most frequent primary cardiac tumor; however, it is a rare, substantial cause of cardiogenic emboli causing a stroke, especially in young adults. A cardiac myxoma has no specific clinical presentation, ranging from constitutional symptoms to non-cardiac symptoms and emboli, which leads to a diagnostic challenge in the clinical process. We report a case of a left atrial myxoma in an adult female who presented with sudden onset of right-sided weakness, headache, and numbness. Imaging confirmed cardiogenic emboli from the cardiac myxoma, which was reflected in an ischemic stroke.

Targeted therapy using nanocomposite delivery systems in cancer treatment: highlighting miR34a regulation for clinical applications.

The clinical application of microRNAs in modern therapeutics holds great promise to uncover molecular limitations and conquer the unbeatable castle of cancer metastasis. miRNAs play a decisive role that regulating gene expression at the post-transcription level while controlling both the stability and translation capacity of mRNAs. Specifically, miR34a is a master regulator of the tumor suppressor gene, cancer progression, stemness, and drug resistance at the cell level in p53-dependent and independent signaling. With changing, trends in nanotechnology, in particular with the revolution in the field of nanomedicine, nano drug delivery systems have emerged as a prominent strategy in clinical practices coupled with miR34a delivery. Recently, it has been observed that forced miR34a expression in human cancer cell lines and model organisms limits cell proliferation and metastasis by targeting several signaling cascades, with various studies endorsing that miR34a deregulation in cancer cells modulates apoptosis and thus requires targeted nano-delivery systems for cancer treatment. In this sense, the present review aims to provide an overview of the clinical applications of miR34a regulation in targeted therapy of cancer.

Papillary Renal Cell Carcinoma: Demographics, Survival Analysis, Racial Disparities, and Genomic Landscape.

Papillary renal cell carcinoma (PRCC) is the second most common histological subtype of renal cell cancer. This research aims to present a large database study highlighting the demographic, clinical, and pathological factors, racial disparities, prognosis, and survival of PRCC. The clinical and demographic data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database, and molecular data was cured from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. PRCC had a median age of diagnosis at 64 years, with a higher incidence in men (77%), and Whites (68%). 70.3% of cases were Grades I-IV (13, 53, 31, and 3%, respectively). In patients with known data, 85% were localized to the kidney, and 84% of cases were 7 cm in size. No metastasis occurred in 97% of the known data. The most common treatment offered was surgical resection (9%). The 5-year overall survival was 79%, with patients undergoing surgery having a 90.6% 5-year survival. Multivariable analysis revealed age > 60 years, Black race, poor histologic differentiation, distant metastases, and tumor size > 10 cm as independent risk factors for mortality. The most common mutations identified from the COSMIC database were MET, KMT2D, KMT2C, ARID1A, and SPEN. PRCC affects male individuals in the sixth decade of life. Increased age, Black race, distant metastases, and tumors > 10 cm are associated with a worse prognosis. Surgical resection offers a favorable survival outcome. Next-generation sequencing (NGS) could identify potentially targetable alterations and future personalized therapeutic approaches.

Biosensing chips for cancer diagnosis and treatment: a new wave towards clinical innovation.

Recent technological advances in nanoscience and material designing have led to the development of point-of-care devices for biomolecule sensing and cancer diagnosis. In situ and portable sensing devices for bedside, diagnosis can effectively improve the patient's clinical outcomes and reduce the mortality rate. Detection of exosomal RNAs by immuno-biochip with increased sensitivity and specificity to diagnose cancer has raised the understanding of the tumor microenvironment and many other technology-based biosensing devices hold great promise for clinical innovations to conquer the unbeatable fort of cancer metastasis. Electrochemical biosensors are the most sensitive category of biomolecule detection sensors with significantly low concentrations down to the atomic level. In this sense, this review addresses the recent advances in cancer detection and diagnosis by developing significant biological sensing devices that are believed to have better sensing potential than existing facilities.

Immune Thrombocytopenia Induced by Helicobacter pylori Infection: A Case Report and Literature Review.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by the production of autoantibodies against the platelet surface antigens. ITP is a diagnosis of exclusion and is further categorized into primary and secondary ITP. The etiology of primary ITP is idiopathic, and secondary ITP is caused by infections and autoimmune disorders. Among infectious etiology of ITP, human immunodeficiency virus, herpes virus, and hepatitis B and C virus are common. Helicobacter pylori (H. pylori) is a rare cause of ITP, and the relationship between ITP and H. pylori is highlighted in the literature. We report a case of ITP in an adult female who presented with hematemesis and petechial rash in the lower limbs. Her initial laboratory results demonstrated thrombocytopenia, and the results of her gastric biopsy and stool antigen were positive for H. pylori. She was diagnosed with ITP induced by H. pylori because additional causes of ITP were not identified. Her clinical improvement and platelet recovery after initiating H. pylori eradication therapy were consistent with H. pylori-induced ITP.

Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Renal Vasculitis After COVID-19 Infection: A Case Report.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a class of autoimmune diseases that can cause kidney failure because of mononuclear cell infiltration and the destruction of small and medium-sized blood vessels. Coronavirus disease 2019 (COVID-19) may trigger or exacerbate autoimmune diseases. We present a case of ANCA-associated vasculitis in a patient with rheumatoid arthritis after a COVID-19 infection, who presented with intermittent hemoptysis and dyspnea and was diagnosed with COVID-19 pneumonia three weeks ago. Her clinical, radiological, and serological picture was concerned with pulmonary-renal syndrome. Her serum was positive for antinuclear antibody and ANCAs, and renal biopsy showed pauci-immune crescentic glomerulonephritis. She was diagnosed clinicopathologically with pauci-immune glomerulonephritis in the setting of rheumatoid arthritis (RA) after a COVID-19 infection. Her condition improved after she was treated with rituximab and pulse dose methylprednisolone.

Myricetin: targeting signaling networks in cancer and its implication in chemotherapy.

The gaps between the complex nature of cancer and therapeutics have been narrowed down due to extensive research in molecular oncology. Despite gathering massive insight into the mysteries of tumor heterogeneity and the molecular framework of tumor cells, therapy resistance and adverse side effects of current therapeutic remain the major challenge. This has shifted the attention towards therapeutics with less toxicity and high efficacy. Myricetin a natural flavonoid has been under the spotlight for its anti-cancer, anti-oxidant, and anti-inflammatory properties. The cutting-edge molecular techniques have shed light on the interplay between myricetin and dysregulated signaling cascades in cancer progression, invasion, and metastasis. However, there are limited data available regarding the nano-delivery platforms composed of myricetin in cancer. In this review, we have provided a comprehensive detail of myricetin-mediated regulation of different cellular pathways, its implications in cancer prevention, preclinical and clinical trials, and its current available nano-formulations for the treatment of various cancers.

In silico-prediction of chloroquine as a multi-targeted drug against CDKN2A signaling network associated with cutaneous malignant melanoma.

Melanoma is one of the most common skin infections, has triggered significant morbidity and mortality across the globe. Previous studies have reported that mutations in CDKN2A signalling network is associated with cutaneous malignant melanoma. In the present study, initially, the BioGrid database was utilized, and then hierarchical clustering was performed to identify the CDKN2A signature pathways. In addition, a GO Enrichment analysis was investigated using DAVID (n=187 genes) toolkit. Subsequently, the cBioPortal cancer genomic platform was exploited using alteration ranked frequency to determine the role of the CDKN2A signaling network in 363 samples of cutaneous malignant melanoma patients and we find that CDKN2A and its close interactors PTEN and HUWE1 show highest mutations. Further, we systematically employed molecular docking approach via MOE to target PTEN, CDKN2A and HUWE1 with chloroquine which is naturally occurring in medicinal plant Nigella sativa (NS) and observed virtuous interactions between all receptors and ligand molecules with a binding energy of -11.379, -10.324 and -9.06 Kcal/mol, respectively. The outcomes obtained stipulate a vigorous research resource for using chloroquine as a multitargeted anticancer drug. This novel evidence should help the development of effective therapeutic compounds for the treatment of cancer. Our results reveal that chloroquine is a relevant and novel potential therapeutic drug for the treatment of melanoma.

Notch Signaling and MicroRNA: The Dynamic Duo Steering Between Neurogenesis and Glioblastomas.

Notch signaling is an evolutionary conserved pathway that plays a central role in development and differentiation of eukaryotic cells. It has been well documented that Notch signaling is inevitable for neuronal cell growth and homeostasis. It regulates process of differentiation from early embryonic stages to fully developed brain. To achieve this streamlined development of neuronal cells, a number of cellular processes are being orchestrated by the Notch signaling. Abrogated Notch signaling is related to several brain tumors, including glioblastomas. On the other hand, microRNAs are small molecules that play decisive role in mediating and modulating Notch signaling. This review discusses the crucial role of Notch signaling in development of nervous system and how this versatile pathway interplay with microRNAs in glioblastoma. This review sheds light on interplay between abrogated Notch signaling and miRNAs in the regulation of neuronal differentiation with special focus on miRNAs mediated regulation of tumorigenesis in glioblastoma. Furthermore, it discusses different aspects of neurogenesis modulated by the Notch signaling that could be exploited for the identification of new diagnostic tools and therapies for the treatment of glioblastoma.

Genistein as a regulator of signaling pathways and microRNAs in different types of cancers.

Cancers are complex diseases orchestrated by a plethora of extrinsic and intrinsic factors. Research spanning over several decades has provided better understanding of complex molecular interactions responsible for the multifaceted nature of cancer. Recent advances in the field of next generation sequencing and functional genomics have brought us closer towards unravelling the complexities of tumor microenvironment (tumor heterogeneity) and deregulated signaling cascades responsible for proliferation and survival of tumor cells. Phytochemicals have begun to emerge as potent beneficial substances aimed to target deregulated signaling pathways. Isoflavonoid genistein is an essential phytochemical involved in regulation of key biological processes including those in different types of cancer. Emerging preclinical evidence have shown its anti-cancer, anti-inflammatory and anti-oxidant properties. Testing of this substance is in various phases of clinical trials. Comprehensive preclinical and clinical trials data is providing insight on genistein as a modulator of various signaling pathways both at transcription and translation levels. In this review we have explained the mechanistic regulation of several key cellular pathways by genistein. We have also addressed in detail various microRNAs regulated by genistein in different types of cancer. Moreover, application of nano-formulations to increase the efficiency of genistein is also discussed. Understanding the pleiotropic potential of genistein to regulate key cellular pathways and development of efficient drug delivery system will bring us a step towards designing better chemotherapeutics.

Clinical applications of artificial intelligence and machine learning in cancer diagnosis: looking into the future.

Artificial intelligence (AI) is the use of mathematical algorithms to mimic human cognitive abilities and to address difficult healthcare challenges including complex biological abnormalities like cancer. The exponential growth of AI in the last decade is evidenced to be the potential platform for optimal decision-making by super-intelligence, where the human mind is limited to process huge data in a narrow time range. Cancer is a complex and multifaced disorder with thousands of genetic and epigenetic variations. AI-based algorithms hold great promise to pave the way to identify these genetic mutations and aberrant protein interactions at a very early stage. Modern biomedical research is also focused to bring AI technology to the clinics safely and ethically. AI-based assistance to pathologists and physicians could be the great leap forward towards prediction for disease risk, diagnosis, prognosis, and treatments. Clinical applications of AI and Machine Learning (ML) in cancer diagnosis and treatment are the future of medical guidance towards faster mapping of a new treatment for every individual. By using AI base system approach, researchers can collaborate in real-time and share knowledge digitally to potentially heal millions. In this review, we focused to present game-changing technology of the future in clinics, by connecting biology with Artificial Intelligence and explain how AI-based assistance help oncologist for precise treatment.

Apigenin role as cell-signaling pathways modulator: implications in cancer prevention and treatment.

Cancer is a complex disease orchestrated by various extrinsic and intrinsic pathways. In recent years, there has been a keen interest towards the development of natural extracts-based cancer therapeutics with minimum adverse effects. In pursuit of effective strategy, a wide variety of natural products-derived compounds have been addressed for their anticancer effects. Apigenin is a naturally-occurring flavonoid present abundantly in various fruits and vegetables. Decades of research have delineated the pharmacological and biological properties of apigenin. Specifically, the apigenin-mediated anticancer activities have been documented in various types of cancer, but the generalized scientific evidence encompassing various molecular interactions and processes, such as regulation of the apoptotic machinery, aberrant cell signaling and oncogenic protein network have not been comprehensively covered. In this sense, in this review we have attempted to focus on the apigenin-mediated regulation of oncogenic pathways in various cancers. We have also addressed the cutting-edge research which has unveiled the remarkable abilities of apigenin to interact with microRNAs to modulate key cellular processes, with special emphasis on the nano-formulations of apigenin that can help their targeted delivery and can be a therapeutic solution for the treatment of various cancers.

Targeting androgen receptor signaling with MicroRNAs and Curcumin: a promising therapeutic approach for Prostate Cancer Prevention and intervention.

Prostate cancer (PC) is a multifactorial disease characterized by the abrogation of androgen receptor signaling. Advancement in microbiology techniques has highlighted the significant role of microRNAs (miRNAs) in the progression of PC cells from an androgen-dependent to an androgen-independent state. At that stage, prostate tumors also fail to respond to currently practiced hormone therapies. So, studies in recent decades are focused on investigating the anti-tumor effects of natural compounds in PC. Curcumin is widely recognized and now of huge prestige for its anti-proliferative abilities in different types of cancer. However, its limited solubility, compatibility, and instability in the aqueous phase are major hurdles when administering. Nanoformulations have proven to be an excellent drug delivery system for various drugs and can be used as potential delivery platforms for curcumin in PC. In this review, a shed light is given on the miRNAs-mediated regulation of androgen receptor (AR) signaling and miRNA-curcumin interplay in PC, as well as on curcumin-based nanoformulations that can be used as possible therapeutic solutions for PC.

Notch Signaling & MicroRNAs - two tumblers of neurogenesis and Gliomas.

Gliomas are one of the most annihilating types of brain tumours having a high rate of annual incidence worldwide. Notch signaling is an evolutionary conserved pathway that regulates differentiation and development. Aberrations in Notch signalling pathways lead to severe pathological state such as the Gliomas. MicroRNAs (miRNAs) are the tiny molecules less than 200 bps in length and regulate a myriad of cellular processes. Categorically, miRNAs are divided in to oncogenic and tumours suppressor miRNAs. Accumulating data have identified miRNAs, which positively or negatively regulate Notch signaling in Gliomas. Here, we have assessed status of our understanding of the interplay between miRNA-base regulation of Notch signaling in gliomas, interaction between Notch signaling and other signaling cascades and have also discussed use of natural compounds that will help us get closer to personalized medicine for gliomas.

MicroRNA Regulation of TRAIL in Renal Carcinoma: Tiny Juggernauts at Work.

Renal Carcinoma (RC) is the ninth most prevalent cancer in men. Advancements in high- throughput technology have begun to scratch the surface of the complex landscape of renal cancer. Development, progression, invasion and metastasis are the key mechanism modulated by the microRNAs (miRNAs). Recent pieces of evidence have delineated the role of these micro steering wheels in the regulation of vital processes of RC biology, therefore miRNAs can be implemented as a new therapeutic target for RC. MiRNAs also negatively affect the process of apoptosis in cancer cells leading to their survival and growth. The role of dysregulated mRNAs in hindering the TRAIL- mediated apoptotic pathway is also known. Therapeutic interventions targeting tumor-suppressive miRNAs to promote apoptosis through extrinsic/intrinsic pathways seem a promising approach for advanced stage and metastatic renal cancers. This article aims to discuss RC-specific microRNAs, their roles in the TRAIL pathway and highlight the distinguished microRNAs that could serve as a diagnostic biomarker and therapeutic targets for this cancer.

Quercetin and MicroRNA Interplay in Apoptosis Regulation in Ovarian Cancer.

The multifaceted nature of ovarian cancer has severely hampered the development of effective therapeutics over the years. The complicate nature of ovarian cancer makes it therapeutically challenging, therefore, there has been a renewed interest in phytochemistry. Phytochemicals have emerged as a potential therapeutic option due to less side effects. Moreover, the signaling inhibition properties have also been studied extensively in recent times. A growing number of data obtained via high-throughput technologies has started to delineate the complex oncogenic signaling networks, thus broadening the therapeutic opportunities. Within the network, microRNAs (miRNAs) have been shown to play a versatile role in the regulation of cancer. Quercetin has been in the spotlight over the years because of its high pharmacological values and substantial evidence has demonstrated its anti-proliferative effect against various types of cancers. Despite the versatility of quercetin, little is known about its anti-proliferative potential towards ovarian cancer. This review sheds some light on quercetin as an alternative therapeutic approach to cancer. Furthermore, we also addresss the interplay between miRNAs and quercetin in the regulation of apoptosis in ovarian cancer.