Inhibitory Effects of Doxycycline on Tumor Progression In vitro and on Metastases in Early-Stage Osteosarcoma Xenografts Mice.

Introduction. Osteosarcoma (OS) is the commonest primary osseous malignant tumor with a high propensity to metastasize in lungs. Pulmonary widespread micrometastatic lesions are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis, effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cells’ growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo. Methods. In vitro, the effect of Dox was measured in MG-63 and 143B human OS cells’ viability, apoptosis, and migration. In vivo, highly metastatic143B cells were orthotopically implanted into the tibia of SCID mice and tumor growth as well as pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined. Results. Dox decreased the viability, inhibited the migration, and induced the apoptosis of OS cells in vitro. In vivo, Dox significantly enhanced tumor necrosis at primary OS sites, similarly to its in vitro effect. It also decreased the expression of Ki67, metalloproteinases 2 and 9 (MMP2 and MMP9), vascular endothelial growth factor A (VEGFA) and Ezrin in primary tumors. It also decreased the circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice in both non-amputated and early amputated xenografts. Conclusions. Our results suggest that adjuvant administration of Dox may decrease OS growth and development of pulmonary metastases. Administration of Dox in combination with surgical resection and standard chemotherapeutic protocols in the early-stages of OS treatment is also supported. Moreover, Dox administration prior to the development of clinically detectable pulmonary macrometastases, is associated with enhanced clinically benefits from its anti-metastatic effect.

Impact of industry on agricultural development in Sylhet region of Bangladesh: Farmer’s perception

The study targets at farmer’s perception and their cognition how they conceive that agricultural performance has been affected and devastated through industrial work. It reviews and investigates the opinion of 25% farmers of two villages from each upazila of two named Madhapur and Habiganj sadar upazila in Sylhet division where Charu Ceramic Industry Limited and Olipur industry are located respectively from mid-September to mid-October, 2021 through survey of questionnaire, interview and group discussion. According to 85% farmers, the industry shades agriculture by imposing an adverse and toxic impact on agricultural exposure and development. Among them, (41.6% and 48.4%) of farmers realize that the industry creates high propensity of losing standard quality of soil and water, respectively. They (40.2%) notice that invasion of several dangerous insects on crops has become prominent and unmanageable near the industrial area. The study represents such kind of realization of farmers to show a salient feature in view of their finding causes and intuition with significant numerical data. Int. J. Agril. Res. Innov. Tech. 11(2): 133-138, Dec 2021

Positive supercoiling buildup is a trigger of E. coli's short-term response to cold shock

Adaptation to cold shock (CS) is a key survival skill of gut bacteria of warm-blooded animals. In E. coli, this skill emerges from a complex transcriptional program of multiple, timely-ordered shifts in gene expression. We identified short-term, cold shock repressed (CSR) genes by RNA-seq and provide evidence that their variability in evolutionary fitness is low and that their responsiveness to cold emanates from intrinsic features. Given that their single-cell variability in protein numbers increases after CS, we hypothesized that the responsiveness of a large portion of CSR genes is triggered by the high propensity for transcription locking due to positive supercoiling buildup (PSB). We then proposed a model of this phenomenon and, in support, show that nearly half of CSR genes are highly responsive to Gyrase inhibition. Also, their response strengths to CS and Gyrase inhibition correlate and most CSR genes increase their single-cell variability in protein numbers. Further, during CS, the cells' nucleoid density increases (in agreement with increased numbers of positive supercoils), their energy levels become depleted (while the resolving of positive supercoils is ATP dependent), and the colocalization of Gyrases and the nucleoid increases (in agreement with increased time length for resolving supercoils). We conclude that high sensitivity to PSB is at the core of the short-term, cold shock responsive transcriptional program of E. coli and propose that this gene feature may be useful for providing temperature sensitivity to chromosome-integrated synthetic circuits.

Primary Testicular Lymphoma a Rare Extra Nodal Involvement of NHL

Primary testicular lymphoma is a collection of neoplasms that constitutes only 1–9% of testicular tumors. Although uncommon in the general population, it is the most common type of malignant testicular tumor in men ≥50 years of age. There are various subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt’s lymphoma and follicular lymphoma. In the adult testis, primary DLBCL represents the most frequent subtype of lymphoma (80–90%), whereas the majority of testicular lymphomas in children consist of secondary involvement by Burkitt’s lymphoma, DLBCL or lymphoblastic lymphoma. The typical clinical sign is a painless testicular mass of variable size that is usually unilateral. Primary testicular lymphoma may be identified during the initial presentation of primary or systemic malignant lymphomas, or during a clinical follow-up of patients with lymphoma. Historically, primary testicular lymphoma has been reported to exhibit a poor prognosis with an overall 5-year survival rate of 17–48%, particularly primary testicular DLBCL, whose clinical behavior has been reported to be aggressive and to demonstrate a high propensity to disseminate to the central nervous system (CNS) and skin at presentation and relapse. The underlying mechanisms responsible for this aggressive behaviour have yet to be elucidated. In the present study, a patient with primary testicular DLBCL was examined from histological examination and immunohistochemical staining in the diagnosis of testicular DLBCL.

Osteosarcoma and Metastasis

Osteosarcoma is the most common primary bone malignancy in adolescents. Its high propensity to metastasize is the leading cause for treatment failure and poor prognosis. Although the research of osteosarcoma has greatly expanded in the past decades, the knowledge and new therapy strategies targeting metastatic progression remain sparse. The prognosis of patients with metastasis is still unsatisfactory. There is resonating urgency for a thorough and deeper understanding of molecular mechanisms underlying osteosarcoma to develop innovative therapies targeting metastasis. Toward the goal of elaborating the characteristics and biological behavior of metastatic osteosarcoma, it is essential to combine the diverse investigations that are performed at molecular, cellular, and animal levels from basic research to clinical translation spanning chemical, physical sciences, and biology. This review focuses on the metastatic process, regulatory networks involving key molecules and signaling pathways, the role of microenvironment, osteoclast, angiogenesis, metabolism, immunity, and noncoding RNAs in osteosarcoma metastasis. The aim of this review is to provide an overview of current research advances, with the hope to discovery druggable targets and promising therapy strategies for osteosarcoma metastasis and thus to overcome this clinical impasse.

Personal Projects’ Appraisals and Compulsive Buying among University Students: Evidence from Galicia, Spain

The appraisal of goal-related constructs, generally, and of personal projects (PP) in particular, is one of the most solid research paths with regard to subjective well-being and health. In the last few years, the appraisal of PP has been linked to such problems as excessive alcohol and marijuana use, but no study has been conducted in the field of compulsive buying (CB). In this study, using Little’s personal-projects-analysis (PPA) methodology, the differences in university students were analyzed in both broad domains (meaning, structure, community, efficacy, and stress) and specific appraisal dimensions in groups with low (n = 293), moderate (n = 191), and high (n = 41) compulsive-buying propensities. The results confirm that the high-propensity group presented the highest significant levels in the domain of stress and the lowest in efficacy, meaning, and structure. As to appraisal dimensions, the group with a high propensity to CB attained statistically lower appraisals in the dimensions of importance, enjoyment, self-identity, absorption, control, time adequacy, progress, and outcome of their projects; the appraisal of the level of stress, difficulty, and conflict increased as the level of involvement in CB increased. These findings have major implications for the design of prevention and intervention programs for this behavioral problem.

Divergent Expression of SPARC, SPARC-L, and SCPP Genes During Jawed Vertebrate Cartilage Mineralization

While cartilage is an ancient tissue found both in protostomes and deuterostomes, its mineralization evolved more recently, within the vertebrate lineage. SPARC, SPARC-L, and the SCPP members (Secretory Calcium-binding PhosphoProtein genes which evolved from SPARC-L) are major players of dentine and bone mineralization, but their involvement in the emergence of the vertebrate mineralized cartilage remains unclear. We performed in situ hybridization on mineralizing cartilaginous skeletal elements of the frog Xenopus tropicalis (Xt) and the shark Scyliorhinus canicula (Sc) to examine the expression of SPARC (present in both species), SPARC-L (present in Sc only) and the SCPP members (present in Xt only). We show that while mineralizing cartilage expresses SPARC (but not SPARC-L) in Sc, it expresses the SCPP genes (but not SPARC) in Xt, and propose two possible evolutionary scenarios to explain these opposite expression patterns. In spite of these genetic divergences, our data draw the attention on an overlooked and evolutionarily conserved peripheral cartilage subdomain expressing SPARC or the SCPP genes and exhibiting a high propensity to mineralize.

Uterine Metastases in a Diagnosed Case of Invasive Ductal Breast Carcinoma: A Rare Presentation

Breast cancer is the commonest cancer among females and has a high propensity to metastasize, but gynaecological organs are rarely affected. We report a case where invasive ductal carcinoma of the breast metastasized to the uterus after initial management with curative intent. Our patient was on tamoxifen, which can cause endometrial hyperplasia and lead to a challenge in eventual diagnosis.

Molecular Dynamics Simulations of hydrophobic peptides that form β-hairpin structures in solution

Peptides designed with residues that have high propensity to occur in β-turns, form β-hairpin structures in apolar solvents as well in polar organic solvents such as dimethyl sulfoxide (DMSO), methanol and varying percentages of DMSO in chloroform (CHCl3). Presumably due to limited solubility, their conformations have not been investigated by experimental methods in water. We have examined the conformations of such designed peptides that fold into well-defined β-hairpin structures facilitated by β-turns, in the crystalline state and in solution, by Molecular Dynamics Simulations (MDS). The peptides fold into β-hairpin structures in water, starting from extended conformation. In DMSO, folding into β-hairpin structures was not observed, starting from extended conformation. However, when the starting structure is in β-hairpin conformation, unfolding is not observed during MDS in DMSO. Water clearly favours folding of short, hydrophobic peptides into β-turn and β-hairpin conformations from extended structures. DMSO does not have a denaturing effect on short, hydrophobic peptides.

A survey of human pilot models for study of Pilot-Induced Oscillation (PIO) in longitudinal aircraft motion

Pilot-Induced Oscillation (PIO), although an old issue, still poses a significant threat to aviation safety. The introduction of new systems in modern aircraft modifies the human–machine interaction and makes it necessary for research to revisit the subject from time to time. Given the need of aircraft manufacturers to constantly perform PIO tests, this study analysed the feasibility of using three different computational pilot models (Tustin, Crossover and Precision) to simulate PIO conditions. Three aircraft models with different levels of propensity to PIO (original, low propensity and high propensity) were tested, as well as two pilot gain conditions (normal and high). Data were collected for a purely longitudinal synthetic task through simulations conducted in MATLAB®. PIO conditions were detect using a tuned PIO detection algorithm (ROVER). Data were analysed in terms of both whether the pilot models triggered a PIO condition and for how long the condition was sustained. The results indicated that the three pilot models only provoked PIO conditions when high gain inputs were applied. Additionally, Crossover was the only pilot model to trigger a PIO for the three aircraft models. There were also significant differences between the pilot models in the total PIO time, as the Tustin model typically sustained the oscillatory condition for longer.