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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Virulent and multidrug-resistant Klebsiella pneumoniae from clinical samples in Balochistan.

Klebsiella pneumoniae is an important pathogen causing hospital-acquired infections in human beings. Samples from suspected patients of K pneumoniae associated with respiratory and urinary tract infections were collected at Bolan Medical Complex, Quetta, Balochistan. Clinical samples (n = 107) of urine and sputum were collected and processed for K pneumoniae isolation using selective culture media. Initially, 30 of 107 isolates resembling Klebsiella spp. were processed for biochemical profiling and molecular detection using gyrase A (gyrA) gene for conformation. The K pneumoniae isolates were analysed for the presence of drug resistance and virulence genes in their genomes. The 21 of 107 (19.6%) isolates were finally confirmed as K pneumoniae pathogens. An antibiogram study conducted against 17 different antibiotics showed that a majority of the isolates are multidrug resistant. All the isolates (100%) were resistant to amoxicillin, cefixime, amoxicillin-clavulanic acid, cefotaxime, and ceftriaxone followed by tetracycline (95.2%), ciprofloxacin and gentamicin (76.2%), sulphamethoxazol (66.7%), nalidixic acid (61.9%), norfloxacine (42.9%), piperacillin-tazobactam (23.8%), cefoperazone-sulbactam (19%), and cefotaxime-clavulanic acid (33.3%), whereas all the isolates showed sensitivity to amikacin, chloramphenicol, and imipenem. The presence of tetracycline, sulphamethoxazol-resistant genes, and extended-spectrum beta-lactamase was reconfirmed using different specific genes. The presence of virulence genes fimH1 and EntB responsible for adherence and enterobactin production was confirmed in the isolates. The high virulence and drug resistance potential of these Klebsiella isolates are of high public health concern. Multidrug resistance and virulence potential in K. pneumoniae are converting these nosocomial pathogens into superbugs and making its management harder.

LncRNA & Wnt signaling in colorectal cancer.

The outlook for new therapeutic approaches is pivotal to ameliorate the deterioration caused by the abrogated Wnt signaling. Long non-coding RNAs (lncRNAs) are tiny molecules that have begun emerging as vital molecular manager for the regulation of various cellular processes at transcription and translation levels in the colorectal cancer (CRC). Targeting Wnt pathway with lncRNA seems a promising approach to eradicate CRC. However, little is known of their active role in commencing both apoptosis and proliferation in CRC. This article  reviews the importance of these molecules in the pathogenesis of CRC and also emphasizes on the development of new therapeutic strategies to cope with the Wnt mediated CRC.

Resveratrol, curcumin, paclitaxel and miRNAs mediated regulation of PI3K/Akt/mTOR pathway: go four better to treat bladder cancer.

Bladder cancer (BC) is a leading cause of death among urothelial malignancies that more commonly affect male population. Poor prognosis and resistance to chemotherapy are the two most important characteristics of this disease. PI3K/Akt/mTOR signaling pathway has been considered pivotal in the regulation of proliferation, migration, invasiveness, and metastasis. Deregulation of PI3K/Akt/mTOR signaling has been found in 40% of bladder cancers. Several microRNAs (miRNAs) have been reported to interact with the PI3K/Akt/mTOR signaling pathway with a different possible role in proliferation and apoptosis in bladder cancer. Thus, miRNAs can be used as potential biomarkers for BC. Natural compounds have been in the spotlight for the past decade due to their effective anti-proliferative capabilities. However, little is known of its possible effects in bladder cancer. The aim of this review is to discuss the interplay between PI3K/Akt/mTOR, miRNAs, and natural compounds and emphasize the importance of miRNAs as biomarkers and resveratrol, curcumin and paclitaxel as a possible therapeutic approach against bladder cancer.

Consanguinity: A blessing or menace at population level?

Consanguinity has highly complex and multifaceted aspects with sociocultural as well as biological debates on its pros and cons. The biological upshot of consanguinity includes the increased homozygosity, which results in manifold increased risk of genetic disorders at family and population levels. On the other hand, in addition to social, cultural, political, and economic benefits, consanguineous marriages have biological advantages at the population level. The consequence of consanguineous marriages is an upsurge in the number of homozygous diseased individuals with fewer chances of mating and reduced chances of survival, therefore evolutionarily confining the transmission of disease alleles to future generations and encouraging its elimination from a population. Protective effects of consanguinity have also been observed in a few diseases in different populations. Although attractive for many reasons, nonconsanguineous marriages will cause risk alleles to spread throughout the population, making most individuals carriers, and ultimately will resume the production of recessive diseases in subsequent generations. Although consanguinity, from an evolutionary point of view, is beneficial at the population level, it increases the risk of diseases in the very next generation. Presently, there is no treatment for most of the genetic disorders; we cannot opt for consanguinity for long-term benefits. Nonconsanguineous marriages are a better strategy by which we may delay disease manifestation for some generations until science offers a viable solution.

A comparative analysis of three distinct fractional derivatives for a second grade fluid with heat generation and chemical reaction.

This article provides a comparison among the generalized Second Grade fluid flow described by three recently proposed fractional derivatives i.e. Atangana Baleanu fractional derivative in Caputo sense (ABC), Caputo Fabrizio (CF) and Constant Proportional-Caputo hybrid (CPC) fractional derivative. The heat mass transfer is observed during the flow past a vertical porous plate that is accelerated exponentially under the effects of the Magneto hydro dynamics. The effects of the heat generation and exponential heating in the temperature boundary layer and chemical reaction at the concentration boundary layer are also analyzed in this article. The flow model is described by three partial differential equations and the set of non-dimensional PDE's is transformed into ODE's by utilization of the integral transform technique (Laplace transform). For the better understanding of the rheological properties of the Second Grade fluid we used the CF, ABC and CPC operators to describe the memory effects. The analytical exact solution of the problem is obtained in the form of G-functions and Mittag Leffler functions. For the physical significance of flow parameters, different parameters are graphed. From this analysis it is concluded that the CPC is the most suitable operator to describe the memory effects.

Advancements in long non-coding RNA-based therapies for cancer: targeting, delivery, and clinical implications.

Long non-coding RNAs (lncRNAs) have been in the spotlight for the past two decades due to their extensive role in regulating a wide range of cellular processes. Development, differentiation, regulation, and modulation are some of the vital cellular cascades coordinated by these molecules. Despite their importance, there has been limited literature on their practical implications in cancer prevention. Advancements in lncRNA biology have enabled the characterization of numerous secondary structures and sequence motifs, which could serve as potential targets for cellular therapies. Several studies have highlighted the involvement of lncRNAs in human pathologies, where they can be targeted by small molecules or antisense oligonucleotides to prevent diseases. However, progress has been hindered by the challenge of developing specific delivery vehicles for targeted delivery. Recent improvements in sequence optimization and nucleotide modification have enhanced drug stability and reduced the immunogenicity of lncRNA-based therapies, yet further advances are needed to fully realize their potential in treating complex diseases like cancer. This review aims to explore current lncRNA biology, their mechanisms of action, nanoformulation strategies, and the clinical trials focused on lncRNA delivery systems.

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.

Numerical exploration of slip effects on second-grade fluid motion over a porous revolving disk with heat and mass transfer.

Revolving-disk systems are employed in various industrial settings including turbine engineering, chemical and food processing industries and others. The current article scrutinizes a second-grade fluid motion generated by an infinite porous disk having partial slip character. Heat transfer induced by heating of the disk surface and by viscous and ohmic heating effects is modeled and analyzed under thermal slip condition. Accompanying mass transfer process with thermophoretic diffusion is also formulated. A self-similar system is obtained akin to the case of no-slip case discussed in a previously published study. The adoption of velocity slip assumption induces non-linearity in the boundary conditions in velocity components. Computational procedure embedded in MATLAB bvp4c platform is opted to simulate the system for full range of slip parameters. In contrast to a previously published work pertaining to the no-slip case, present numerical methodology gives accurate results for wide ranges of Prandtl number and elasticity parameter. Boundary layer formations above the disk are examined under various controlling parameters. A comparative assessment of slip and no-slip cases is presented through both graphical illustrations and tabulated results for the resisting torque, the Nusselt number and the Sherwood number. Current numerical findings match very well with the existing homotopy solutions for the no-slip case. The presence of a wall slip mechanism leads to a clear suppression of all the velocity components. Furthermore, an augmentation in the thermal/concentration slip coefficient significantly reduces the thermal/solutal penetration depth. Additionally, we observe a noticeable increase in the driving torque as the elasticity parameter enhances. The slip action of the surface is also predicted to raise the torque required by the disk.