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Introduction: Knowledge of the safe zone of mini-implant placement guides clinicians in choosing where to place mini-implants. Several studies evaluated the safe zone for mini-implants placement, but only a very few previous studies have taken different skeletal patterns into account when assessing measurements. Objective: The purpose of this cross-sectional, comparative study was to compare the inter-radicular distance and buccal cortical bone thickness in Class I and Class II skeletal malocclusion patterns. Materials and Methods: A total of 62 CBCT images of patients with Class I and Class II skeletal malocclusion were obtained from the records of the department of Oral medicine and Radiology, Kathmandu University Teaching Hospital. The inter-radicular distance and buccal cortical bone thickness were measured at four different heights (2, 4, 6 and 8 mm) from the CEJ towards the apex. These measurements were measured between different skeletal pattern and gender with independent t-test. The intergroup comparison at different height from CEJ was done with ANOVAfollowed by Tukey's post-hoc test to see the difference within the category. Result: There was a statistically significant difference observed in the inter-radicular distance between the maxillary first and second premolars at a height of 6 mm between Class I and Class II malocclusion patterns (p = 0.03). There were differences observed in the inter-radicular distance of the mandible at a different height based on skeletal malocclusion pattern, which was not statistically significant (p > 0.05). The buccal cortical bone thickness between the maxillary central and lateral incisors at the height of 2 mm from CEJ between Class I and Class II skeletal malocclusion patterns was statistically significant (p = 0.01). The buccal cortical bone thickness of the mandible at different heights based on skeletal malocclusion pattern there were differences observed which were not statistically significant (p > 0.05). Conclusion: The inter-radicular distance and buccal cortical bone thickness could be influenced by different skeletal patterns and tend to increase from the CEJ to the apex in both Class I and Class II skeletal patterns.

Microbes are a huge contributor to people's health around the world since they produce a lot of beneficial secondary metabolites. Cyanobacteria are photosynthetic prokaryotic bacteria cosmopolitan in nature. Adaptability of cyanobacteria to wide spectrum of environment can be contributed to the production of various secondary metabolites which are also therapeutic in nature. As a result, they are a good option for the development of medicinal molecules. These metabolites could be interesting COVID-19 therapeutic options because the majority of these compounds have demonstrated substantial pharmacological actions, such as neurotoxicity, cytotoxicity, and antiviral activity against HCMV, HSV-1, HHV-6, and HIV-1. They have been reported to produce a single metabolite active against wide spectrum of microbes like Fischerella ambigua produces ambigols active against bacteria, fungi and protozoa. Similarly, Moorea producens produces malygomides O and P, majusculamide C and somocystinamide which are active against bacteria, fungi and tumour cells, respectively. In addition to the above, Moorea sp. produce apratoxin A and dolastatin 15 possessing anti cancerous activity but unfortunately till date only brentuximab vedotin (trade name Adcetris), a medication derived from marine peptides, for the treatment of Hodgkin lymphoma and anaplastic large cell lymphoma has been approved by FDA. However, several publications have effectively described and categorised cyanobacterial medicines based on their biological action. In present review, an effort is made to categorize cyanobacterial metabolites on the basis of their phycochemistry. The goal of this review is to categorise cyanobacterial metabolites based on their chemical functional group, which has yet to be described.

Purpose Neglected tropical diseases (NTDs) are a set of infectious diseases that primarily affect low-income countries situated near the equator. Effective diagnostic tools hold the key to stemming the spread of these infectious diseases. However, specificity is a major concern associated with current diagnostic protocols. In this regard, electrochemical deoxyribonucleic acid (DNA) biosensors could play a crucial role, as highlighted by renewed interest in their research. The purpose of this study was to highlight the current scenario for the design and development of biosensors for the detection of NTDs related pathogens. This review highlights the different types of factors involved and the modifications used to enhance sensor properties. Design/methodology/approach The authors discuss the potential of electrochemical DNA biosensors as efficient, affordable diagnostic tools for the detection of pathogens associated with NTDs by reviewing available literature. This study discusses the biosensor components, mainly the probe selection and type of electrodes used, and their potential to improve the overall design of the biosensor. Further, this study analyses the different nanomaterials used in NTD-based electrochemical DNA biosensors and discusses how their incorporation could improve the overall sensitivity and specificity of the biosensor design. Finally, this study examines the impact such techniques could have in the future on mass screening of NTDs. Findings The findings provide an in-depth analysis of electrochemical DNA biosensors for the detection of pathogens associated with NTDs. Originality/value This review provides an update on the different types and modifications of DNA biosensors that have been designed for the diagnosis of NTD-related pathogens.

In Azospirillum brasilense, an extra-cytoplasmic function σ factor (RpoE10) shows the characteristic 119 amino acid long C-terminal extension found in ECF41-type σ factors, which possesses three conserved motifs (WLPEP, DGGGR, and NPDKV), one in the linker region between the σ

This article describes the typical expression for the wholly exposed area of PVT-CPC Collectors built-in double slope solar still matching with the Hottel-Whillier-Bliss expression for (FPC). The drawbacks in the partly exposed area of photovoltaic thermal collectors namely high manufacturing cost, servicing cost is more and Low thermal movements of molecules owing top loss. The above drawbacks of partly exposed area of PVT-CPC (for N-identical numbers) have been completely discussed in wholly exposed area of PVT combined with CPC collector for the same value of watt peak. The typical expression for the different parts of PVT-CPC built-in with double slope solar still has also been development. The mathematical term for our current work is also compared with cases: (1) PVT flat plate collector double slope solar unit (2) Flat plate collector included with double slope solar still (conventional) and (3) Double slope distiller unit (passive). The instant efficiency of proposed work is found to be better than case (1) , (3) but a little less than the case (2) .

Invasion assay of ARCaPM-TBX2 and ARCaPM-Neo cells

Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here, we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell–derived, atypically large (1–10 μm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific. LO internalization induced reprogramming of human normal prostate fibroblasts as reflected by high levels of α-SMA, IL6, and MMP9. In turn, LO-reprogrammed normal prostate fibroblasts stimulated endothelial tube formation in vitro and promoted tumor growth in mice. Activation of stromal MYC was critical for this reprogramming and for the sustained cellular responses elicited by LO, both in vitro and in vivo in an AKT1-dependent manner. Inhibition of LO internalization prevented activation of MYC and impaired the tumor-supporting properties of fibroblasts. Overall, our data show that prostate cancer–derived LO powerfully promote establishment of a tumor-supportive environment by inducing a novel reprogramming of the stroma. This mechanism offers potential alternative options for patient treatment. Cancer Res; 77(9); 2306–17. ©2017 AACR.

Supplementary Table 1: RT-qPCR primers sequences.

Legend to Supplementary Figures

Plot showing relative protein expression of TBX2 and WNT3A in human PCa cell lines

Supplementary Table 2: Master regulator analysis (MRA), using TF-target interaction information collected from public databases, including the Biomolecular Interaction Network database (BIND), EdgeExpress database (EEDB), Transcriptional Regulatory Element database (TRED), ChIP Enrichment Analysis (ChEA), ChIPBase, and hmChIP, of 274 TF, was performed on 207 differentially expressed genes (DEG) (FDR < 0.1 and fold change {greater than or equal to} 1.5)

Invasion assay of PC3 (TBX2DN+WNT3A, TBX2DN, and Neo)cells with the addition of SFRP-2

Additional data on Akt1 in circulating EVs

Additional data on LO internalization

Supplementary Materials and Methods

Schematic depiction of WNT3A gene promoter, and ChIP analysis of LNCaP-TBX2 and LNCaP-Neo cells to assess the binding of TBX2 on WNT3A promoter

Additional data on MYC activation by LO

Micro-CT images of mouse tibiae injected with ARCaPM-TBX2 and ARCaPM-Neo cells

Identification of factors that mediate visceral and bone metastatic spread and subsequent bone remodeling events is highly relevant to successful therapeutic intervention in advanced human prostate cancer. TBX2, a T-box family transcription factor that negatively regulates cell-cycle inhibitor p21, plays critical roles during embryonic development, and recent studies have highlighted its role in cancer. Here, we report that TBX2 is overexpressed in human prostate cancer specimens and bone metastases from xenograft mouse models of human prostate cancer. Blocking endogenous TBX2 expression in PC3 and ARCaPM prostate cancer cell models using a dominant-negative construct resulted in decreased tumor cell proliferation, colony formation, and invasion in vitro. Blocking endogenous TBX2 in human prostate cancer mouse xenografts decreased invasion and abrogation of bone and soft tissue metastasis. Furthermore, blocking endogenous TBX2 in prostate cancer cells dramatically reduced bone-colonizing capability through reduced tumor cell growth and bone remodeling in an intratibial mouse model. TBX2 acted in trans by promoting transcription of the canonical WNT (WNT3A) promoter. Genetically rescuing WNT3A levels in prostate cancer cells with endogenously blocked TBX2 partially restored the TBX2-induced prostate cancer metastatic capability in mice. Conversely, WNT3A-neutralizing antibodies or WNT antagonist SFRP-2 blocked TBX2-induced invasion. Our findings highlight TBX2 as a novel therapeutic target upstream of WNT3A, where WNT3A antagonists could be novel agents for the treatment of metastasis and for skeletal complications in prostate cancer patients. Cancer Res; 77(6); 1331–44. ©2017 AACR.

Quantitative Real-Time RT-PCR and Invasion assay of LNCaP-TBX2 and LNCaP-Neo cells

Cancer Outlier Profile Analysis (COPA) in Oncomine 4.4 showing TBX2 over-expression in PCa microarray data sets

Additional Experimental Procedure Information

Ovarian cancer, an aggressive epithelial cancer, remains a major cause of cancer mortality worldwide among women, but it can be diagnosed at an early stage also. Surgical removal of ovarian tumour is a good option for the initial treatment, but this is suitable only at the early stage of cancer. Surgery and other therapies like chemotherapy, hormone role therapy and immunotherapy alone are insufficient for the treatment of today’s advanced ovarian cancer. The aim of this book chapter is to review the use of nano-particles in the treatment of ovarian cancer, along with surgery. It is believed that nano therapies have lots of advantages like they stabilize drugs in our body, deliver and penetrate the drugs to tumour-specific cells and can profile the toxicity of chemotherapy. This book chapter also covers the development of nanotherapies, types of nanocarriers and their role in ovarian cancer diagnosis and treatment

Purpose Coronavirus Disease 2019 (COVID-19) severity and Diabetes mellitus affect each other bidirectionally. However, the cause of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection on the incidence of diabetes is unclear. In the SARS-CoV-2-infected cells, host microRNAs (miRNAs) may target the native gene transcripts as well as the viral genomic and subgenomic RNAs. Here, we investigated the role of miRNAs in linking Diabetes to SARS-CoV-2 infection in the human pancreas. Methods Differential gene expression and disease enrichment analyses were performed on an RNA-Seq dataset of human embryonic stem cell-derived (hESC) mock-infected and SARS-CoV-2-infected pancreatic organoids to obtain the dysregulated Diabetes-associated genes. The miRNA target prediction for the Diabetes-associated gene transcripts and the SARS-CoV-2 RNAs has been made to determine the common miRNAs targeting them. Minimum Free Energy (MFE) analysis was done to identify the miRNAs, preferably targeting SARS-CoV-2 RNAs over the Diabetes-associated gene transcripts. Results The gene expression and disease enrichment analyses of the RNA-Seq data have revealed five biomarker genes, i.e., CP, SOCS3, AGT, PSMB8 and CFB that are associated with Diabetes and get significantly upregulated in the pancreas following SARS-CoV-2-infection. Four miRNAs, i.e., hsa-miR-298, hsa-miR-3925-5p, hsa-miR-4691-3p and hsa-miR-5196-5p, showed preferential targeting of the SARS-CoV-2 genome over the cell’s Diabetes-associated messenger RNAs (mRNAs) in the human pancreas. Conclusion Our study proposes that the differential targeting of the Diabetes-associated host genes by the miRNAs may lead to diabetic complications or new-onset Diabetes that can worsen the condition of COVID-19 patients. Supplementary Information The online version contains supplementary material available at 10.1007/s40618-021-01693-3.

Telomere length is primarily controlled by the enzyme telomerase, but being chromatin structures, telomeres undergo epigenetic regulation for their maintenance and function. Altered telomere length among cancer cells combined with shorter telomere length in cancer-associated stromal cells, strongly implicated with progression to prostate cancer metastasis and cancer death and providing a novel target for therapeutics. Transforming growth factor-β (TGF-β) signaling pathways are well-recognized for their role in stromal-epithelial interactions responsible for prostate androgen responsiveness, promoting tumorigenesis. However, the underlying mechanism remains unclear. We sought to establish a role for TGF-β in the regulation of telomere length in mouse and human prostate fibroblast. Polymerase chain reaction (PCR)-based telomere length measuring methods are widely used due to their repeatability and reproducibility. Using real-time RT-PCR-based telomere length measuring method, we identified that TGF-beta regulates telomere length via increased expression of histone methyltransferase, Suv39h1, which in turn affected histone methylation levels at the telomeric ends. Moreover, treatment of DAPT and non-steroidal antiandrogen bicalutamide demonstrated that notch and androgen signaling co-operated with TGF-ß in regulating stromal telomere length. Telomere variation in tumor cells and non-tumor cells within the tumor microenvironment greatly facilitates the clinical assessment of prostate cancer; therefore, understanding stromal telomere length regulation mechanism will hold significant prospects for cancer treatment, diagnosis, and prognosis.The online version contains supplementary material available at 10.1007/s13205-022-03346-5.

It has been well established that N-acetylcysteine, a glutathione precursor is a major antioxidant with excellent anti-inflammatory properties and has been administered for the treatment of a different diseases. The poor bioavailability associated with NAC has been a major hurdle in administering effective doses to achieve desired drug efficacy. A safe steady release of NAC from drug delivery vehicles could enhance the drug effectiveness and help control the concentration of the drug being administered. PLGA is a widely used polymer in drug delivery studies due to its biocompatibility and excellent pharmacokinetic properties exhibited by the polymer when synthesized as nanoparticles. Since its approval by the Food and Drug Administration as a safe mode of drug delivery, it is constantly being explored for its versatile use encapsulation of different types of drugs to enhance its efficacy. Recent studies have highlighted the potential of drug encapsulated nanoparticles as an effective therapeutic strategy for a broad range of diseases such as cancer and other inflammatory conditions. In this study we attempted to encapsulate NAC in PLGA nanoparticles and optimize the concentration of surfactant used through DLS, zeta potential, FTIR and SEM imaging.

Androgen receptor signaling inhibitors (ARSIs) are standard of care for advanced prostate cancer (PCa) patients. Eventual resistance to ARSIs can include the expression of androgen receptor (AR) splice variant, AR-V7, expression as a recognized means of ligand-independent androgen signaling. We demonstrated that interleukin (IL)-6-mediated AR-V7 expression requires bone morphogenic protein (BMP) and CD105 receptor activity in both PCa and associated fibroblasts. Chromatin immunoprecipitation supported CD105-dependent ID1- and E2F-mediated expression of RBM38. Further, RNA immune precipitation demonstrated RBM38 binds the AR-cryptic exon 3 to enable AR-V7 generation. The forced expression of AR-V7 by primary prostatic fibroblasts diminished PCa sensitivity to ARSI. Conversely, downregulation of AR-V7 expression in cancer epithelia and associated fibroblasts was achieved by a CD105-neutralizing antibody, carotuximab. These compelling pre-clinical findings initiated an interventional study in PCa patients developing ARSI resistance. The combination of carotuximab and ARSI (i.e., enzalutamide or abiraterone) provided disease stabilization in four of nine assessable ARSI-refractory patients. Circulating tumor cell evaluation showed AR-V7 downregulation in the responsive subjects on combination treatment and revealed a three-gene panel that was predictive of response. The systemic antagonism of BMP/CD105 signaling can support ARSI re-sensitization in pre-clinical models and subjects that have otherwise developed resistance due to AR-V7 expression.

Eukaryotic cells are capable of internalizing different types of cargo by plasma membrane ruffling and forming vesicles in a process known as endocytosis. The most extensively characterized endocytic pathways are clathrin-coated pits, lipid raft/caveolae-mediated endocytosis, phagocytosis, and macropinocytosis. Macropinocytosis is unique among all the endocytic processes due to its nonselective internalization of extracellular fluid, solutes, and membrane in large endocytic vesicles known as macropinosomes with unique susceptibility toward Na+/H+ exchanger inhibitors. Range of cell types capable of macropinocytosis and known to play important role in different physiological processes, which include antigen presentation, nutrient sensing, migration, and signaling. Understanding the physiological function of macropinocytosis will be helpful in filling the gaps in our knowledge and which can be exploited to develop novel therapeutic targets. In this chapter, we discuss the different molecular mechanisms that initiate the process of macropinocytosis with special emphasis on proteins involved and their diversified role in different cell types.

Despite extraordinary advances that have been made in cancer therapy, the number of cancer cases continue to surge, making it the leading cause of death across the world. As a result, early detection is one of the key aspects in the battle against the disease. Screening and early diagnosis play a pivotal role for effective treatment and to lower the cancer mortality rate. Cancer nanotechnology is a new branch in biology that provides a link between nanotechnology and clinical cancer research. Moreover, it also aims to integrate the advancements made in the manufacture of nanoscale devices with cellular and molecular components associated with cancer diagnosis and therapy. Understanding these new technologies is crucial to integrating these practices into clinical settings. This novel approach has facilitated the conjugation of nanoscale devices with agents such as tumor-specific li-gands, antibodies, and imaging probes. This review summarizes the advancements made in nanotechnology based approaches in diagnosing cancer. Coupling of nanoparticles with targeting molecules enables an efficient interaction between biological systems with extraordinary accuracy. The progress associated with nanoscale devices such as metal based nanomaterials, exosomes, magnetic nanoparticles, in addition to quantum dots and lab on chip devices with regard to diagnostic applications has been discussed. We summarize how nanoparticles take advantage of the tumor microenvironment for targeting cancer cells. Further, the review outlines the drawbacks, challenges, and future prospects associated with these techniques as effective strategies to replace current clinical trends.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent form of cancer worldwide. Despite advancements made in treatment strategies, the fatality rate of HNSCC is very high. An accumulating body of evidence suggests that epigenetic modification of histones plays an influential role in the development and progression of the disease. In this review we discuss the role of epigenetic modifications in HNSCC and the inter-relationships of human papillomavirus oncoproteins and histone-modifying agents. Further, we explore the possibility of identifying these modifications as biomarkers for their use as drugs in treatment strategies.Head and neck squamous cell carcinoma (HNSCC) is the most common kind of head and neck cancer. HNSCC can develop therapeutic resistance, making therapy more difficult. Many studies have found that epigenetic events play a key role in HNSCC. Better understanding epigenetic regulation could help discovery of biomarkers that help detect and diagnose HNSCC. This review will present recent studies, showing the importance of epigenetic regulation targeting histone modifications in the development of HNSCC.

The SARS-CoV-2 viral genome is mutating and evolving into new variations, including the recently discovered Delta and Omicron. In this study, we used and evaluated our notion of differential targeting of SARS-CoV-2 variant genomes by microRNAs (miRNAs) of the infected human pancreas. We found that even with UTR mutations, the Delta, Omicron, and original Wuhan variations’ genomes would be differentially targeted by the host pancreas cell’s native miRNAs in the same way. The miRNAs show a difference in Minimal Free Energy (MFE) with the different viral variants’ genomes; however, they would still be responsible for the upregulation of the diabetes-associated genes.

The Digital Age has transformed the ways in which we function in any and every sphere of our lives. It has cracked open the doors of all the possibilities of innovations and the unending scope of transformation which technology can bring about in our lives. Though it is the truth that technology does not always have a positive impact on human lives, but the humans can also not deny the ease and efficiency it is capable of bringing about in the overall development of their personalities and the progress of their nations. Today, technology is spreading its roots to all sectors of economy, and the major impact of the same is seen in the boost it has given to the Agricultural Sector. With flying drones to giving advisory services to farmers in the remotest areas of the countries to even digitalizing their finances to facilitateeasy access to low-cost technology digitalization has come as a blessing to us. This paper is thus an in-depth analysis of the role played by Technology in the Agricultural sector, whereby, the author shall also delve into the details of the policies and technological innovations that have changed the ways in which the agricultural-sector operates today. &nbsp

In this paper, studies have been made on some self-superposable motion of incompressible fluid is confocal Paraboloidal ducts. The boundary conditions have been neglected therefore the solutions contain a set of constants. Pressure distribution and the nature of vorticity are discussed. Tendency of irrotationality of the fluid flow is also determined. The aim of the paper is to introduce a method for solving the basic equations of fluid dynamics in confocal paraboloidal coordinates by using the property of self superposability. &nbsp