Osteoarthritis (OA), a chronic degenerative disease characterized mainly by damage to the articular cartilage, is increasingly relevant to the pathological processes of senescence, apoptosis, autophagy, proliferation, and differentiation of chondrocytes. Clinical strategies for osteoarthritis can only improve symptoms and even along with side effects due to age, sex, disease, and other factors. Therefore, there is an urgent need to identify new ideas and targets for current clinical treatment. The tumor suppressor gene p53, which has been identified as a potential target for tumor therapeutic intervention, is responsible for the direct induction of the pathological processes involved in OA modulation. Consequently, deciphering the characteristics of p53 in chondrocytes is essential for investigating OA pathogenesis due to p53 regulation in an array of signaling pathways. This review highlights the effects of p53 on senescence, apoptosis, and autophagy of chondrocytes and its role in the development of OA. It also elucidates the underlying mechanism of p53 regulation in OA, which may help provide a novel strategies for the clinical treatment of OA.

Pyroptosis is a novel type of cell death observed in various diseases. Our study aimed to investigate the relationship between pyroptosis-associated-long non-coding RNAs (lncRNAs), immune infiltration, and expression of immune checkpoints in the setting of lung adenocarcinoma and the prognostic value of pyroptosis-related lncRNAs. RNA-seq transcriptome data and clinical information from The Cancer Genome Atlas (TCGA) were downloaded, and consensus clustering analysis was used to separate the samples into two groups. Least absolute shrinkage and selection operator (LASSO) analyses were conducted to construct a risk signature. The association between pyroptosis-associated lncRNAs, immune infiltration, and expression of immune checkpoints were analysed. The cBioPortal tool was used to discover genomic alterations. Gene set enrichment analysis (GSEA) was utilized to investigate downstream pathways of the two clusters. Drug sensitivity was also examined. A total of 43 DEGs and 3643 differentially expressed lncRNAs were identified between 497 lung adenocarcinoma tissues and 54 normal samples. A signature consisting of 11 pyroptosis-related lncRNAs was established as prognostic for overall survival. Patients in the low-risk group have a significant overall survival advantage over those in the high-risk group in the training group. Immune checkpoints were expressed differently between the two risk groups. Risk scores were validated to develop an independent prognostic model based on multivariate Cox regression analysis. The area under time-dependent receiver operating characteristic curve (AUC of the ROC) at 1-, 3-, and 5-years measured0.778, 0.757, and 0.735, respectively. The high-risk group was more sensitive to chemotherapeutic drugs than the low-risk group. This study demonstrates the association between pyroptosis-associated lncRNAs and prognosis in lung adenocarcinoma and enables a robust predictive signature of 11 lncRNAs to inform overall survival.

To observe the expression changes of P2 protein in cochlear spiral ganglion cells before and after noise injury, and to explore the relationship between the changes of purinergic receptors in spiral ganglion cells and noise-induced hearing loss, so that the signal transduction of purinergic receptors can be used to treat SNHL The target point provides a theoretical basis. The experimental animals were randomly divided into normal and experimental groups. The experimental group was given 120 dB white noise continuous exposure for 10 days and 3 h a day. The auditory brainstem response was measured before and after the noise exposure. After the noise exposure, the two groups of animals were collected. Do immunofluorescence staining, western blot, fluorescence real-time quantitative PCR to observe the expression of P2 protein. The average hearing threshold of the animals in the experimental group increased to 38.75 ± 6.44 dB SPL after 7 days of noise exposure, and the high-frequency hearing loss was lower and severe; the average hearing threshold increased to 54.38 ± 6.80 dB SPL after 10 days of noise exposure, and the hearing loss at 4 k Hz was relatively high. Light; Frozen sections of cochlear spiral ganglion cells and staining of isolated spiral ganglion cells found that P2X2, P2X3, P2X4, P2X7, P2Y2, and P2Y4 proteins were all expressed in cochlear spiral ganglion cells before noise exposure. Among them, P2X3 expression increased and P2X4, the down-regulation of P2Y2 expression was statistically significant (P < 0.05); Western blot and real-time quantitative PCR detection results showed that the expression of P2X3 was significantly increased after noise exposure than before noise exposure (P < 0.05), and P2X4 and P2Y2 were expressed after noise exposure The amount was significantly lower than before noise exposure (P < 0.05). (Figure. 4). After noise exposure, the expression of P2 protein is upregulated or downregulated. By affecting the Ca2+ cycle, the transmission of sound signals to the auditory center is blocked, which provides a theoretical basis for the signal transduction of purinergic receptors to become a target for the treatment of SNHL.

Gene transfer technology has great value in ornamental plants toward the generation of varieties with new ornate characteristics. In the previous studies through the transformation of cyclamen, hygromycin was mainly used as a selective marker. However, there have been some drawbacks associated with hygromycin usage as a selecting agent. Therefore, in the current study, the optimization of kanamycin concentration in the regeneration media has been considered. Subsequently, the plant transformation using three different in vitro explants from three Cyclamen persicum cultivars using three Agrobacterium tumefaciens strains has been examined. Accordingly, the optimal kanamycin concentrations for regeneration from root and leaf explants were determined as 10 mg/L and for microtuber explants as 30 mg/L. The successful gene transformation in the antibiotic-resistant shoots were examined by PCR and UV-equipped microscopes. The gfp reporter gene transfer resulted in the highest efficiency of transformation (60%) to date, from the leaf explants of cv. Pure White inoculated with Agrobacterium tumefaciens strain LBA4404. In contrast, the lowest gene transfer efficiency (25%) was observed in root explants of cv. Dark Violet and cv. Neon Pink inoculated with strains GV3101 and AGL-1, respectively. The results of the current project are expandable to the subsequent investigations of Cyclamen persicum transformation.

The efficiency of Cladophora species for the removal of Reactive Orange 107 (RO107) from the aqueous solution was evaluated through batch adsorption studies by optimising various process parameters such as pH (3-8), dye concentration (100-500 mg/l), biosorbent concentration (100-500 mg/l), temperature (25-45 °C) and contact time (12-108 h). The results revealed that the optimum conditions for RO107 decolourisation (87%) was found on 72 h of incubation with 100 mg/l dye concentration amended with 200 mg/l biosorbent at pH 6 at 25 °C. The mechanism of dye adsorption was evaluated using isotherms, kinetics and thermodynamic models. The experimental data fitted well with Langmuir isotherm and pseudo-second-order kinetic models. Thermodynamic studies revealed that the adsorption process was endothermic, spontaneous and feasible in nature. Recovery of RO107 from the Cladophora sp. was maximum when 0.1 M HNO3 was used as an eluent. UV-Visible, FT-IR and SEM analyses reveal the interaction between the biosorbent-adsorbate and confirm the process of decolourisation by Cladophora sp. In order to evaluate the nature of the untreated and treated dye solutions, toxicological studies were conducted and the results revealed that the treated dye solution was non- toxic as compared with untreated dye solution. The results of the docking study proved that there was a substantial binding energy between RO107 and the protein (Cytochrome C6) of Cladophora sp. Hence, Cladophora sp. proves to be a promising biosorbent to decolourise RO107 and its potential can be explored in the textile sectors.

Modern biological science is trying to solve the fundamental complex problems of molecular biology, which include protein folding, drug discovery, simulation of macromolecular structure, genome assembly, and many more. Currently, quantum computing (QC), a rapidly emerging technology exploiting quantum mechanical phenomena, has developed to address current significant physical, chemical, biological issues, and complex questions. The present review discusses quantum computing technology and its status in solving molecular biology problems, especially in the next-generation computational biology scenario. First, the article explained the basic concept of quantum computing, the functioning of quantum systems where information is stored as qubits, and data storage capacity using quantum gates. Second, the review discussed quantum computing components, such as quantum hardware, quantum processors, and quantum annealing. At the same time, article also discussed quantum algorithms, such as the grover search algorithm and discrete and factorization algorithms. Furthermore, the article discussed the different applications of quantum computing to understand the next-generation biological problems, such as simulation and modeling of biological macromolecules, computational biology problems, data analysis in bioinformatics, protein folding, molecular biology problems, modeling of gene regulatory networks, drug discovery and development, mechano-biology, and RNA folding. Finally, the article represented different probable prospects of quantum computing in molecular biology.

The rhizobacterial isolate SP-167 exhibited considerable phosphate solubilization, IAA production, exo-polysaccharides, proline, APX, and CAT at a concentration of 6% NaCl (w/v). 16S rDNA sequencing and BLAST analysis showed that isolate SP-167 was Klebsiella sp. In this study, T2 and T8 consortium was developed on the basis of the compatibility of isolate SP-167 with Kluyvera sp. and Enterobacter sp. At 6% NaCl (w/v) concentration, T2 and T8 showed increased PGP properties such as phosphate solubilization, IAA, Proline activity, CAT, POD, and EPS than isolate SP-167. The maximum increase in shoot length was recorded in T2-treated maize plants as compared to the control after 60 days in 1% NaCl stress. The N, P, and K content of leaves were significantly increased in maize plants with the inoculation of both the T2 and T8 consortium. The electrical conductivity of soil was decreased significantly in the T2 inoculated 1% NaCl (w/v) treated pot after 30, 60, and 90 days. In this study, soil enzymes DHA and PPO were significantly increased in both T2 and T8 treated combinations. The Na concentration in root and shoot were significantly decreased in T8 inoculated plant than in T2, as confirmed by the translocation factor study.

Cuproptosis is a type of programmed cell death triggered by accumulation of intracellular copper which was considered closely related to tumor progression. The study of cuproptosis in multiple myeloma (MM) is however limited. To determine the prognostic significance of cuproptosis-related gene signature in MM, we interrogated gene expression and overall survival with other available clinical variables from public datasets. Four cuproptosis-related genes were included to establish a prognostic survival model by least absolute shrinkage and selection operator (LASSO) Cox regression analysis, which showed a good performance on prognosis prediction in both training and validation cohorts. Patients with higher cuproptosis-related risk score (CRRS) exhibited worse prognosis compared with lower risk score. Survival prediction capacity and clinical benefit were elevated after integrating CRRS to existing prognostic stratification system (International Staging System, ISS or Revised International Staging System, RISS) both on 3-year and 5-year survival. Based on CRRS groups, functional enrichment analysis and immune infiltration in bone marrow microenvironment revealed correlation between CRRS and immunosuppression. In conclusion, our study found that cuproptosis-related gene signature is an independent poor prognostic factor and functions negatively on immune microenvironment, which provides another perspective on prognosis assessment and immunotherapy strategy in MM.

Myocardial infarction (MI) is an extremely severe cardiovascular disease, which ranks as the leading cause of sudden death worldwide. Studies have proved that cardiac injury following MI can cause cardiomyocyte apoptosis and myocardial fibrosis. Bilobalide (Bilo) from Ginkgo biloba leaves have been widely reported to possess excellent cardioprotective effects. However, concrete roles of Bilo in MI have not been investigated yet. We here designed both in vitro and in vivo experiments to explore the effects of Bilo on MI-induced cardiac injury and the underlying mechanisms of its action. We conducted in vitro experiments using oxygen-glucose deprivation (OGD)-treated H9c2 cells. Cell apoptosis in H9c2 cells was assessed by conducting flow cytometry assay and evaluating apoptosis-related proteins with western blotting. MI mouse model was established by performing left anterior descending artery (LAD) ligation. Cardiac function of MI mice was determined by assessing ejection fraction (EF), fractional shortening (FS), left ventricular end-systolic diameter (LVESD), and left ventricular end-diastolic diameter (LVEDD). Histological changes were analyzed, infarct size and myocardial fibrosis were measured by hematoxylin and eosin (H&E) and Masson staining in cardiac tissues from the mice. The apoptosis of cardiomyocytes in MI mice was assessed by TUNEL staining. Western blotting was applied to detect the effect of Bilo on c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinases (p38 MAPK) signaling both in vitro and in vivo. Bilo inhibited OGD-induced cell apoptosis and lactate dehydrogenase (LDH) release in H9c2 cells. The protein levels of p-JNK and p-p38 were significantly downregulated by Bilo treatment. SB20358 (inhibitor of p38) and SP600125 (inhibitor of JNK) suppressed OGD-induced cell apoptosis as Bilo did. In MI mouse model, Bilo improved the cardiac function and significantly reduced the infarct size and myocardial fibrosis. Bilo inhibited MI-induced cardiomyocytes apoptosis in mice. Bilo suppressed the protein levels of p-JNK and p-p38 in cardiac tissues from MI mice. Bilo alleviated OGD-induced cell apoptosis in H9c2 cells and suppressed MI-induced cardiomyocyte apoptosis and myocardial fibrosis in mice via the inactivation of JNK/p38 MAPK signaling pathways. Thus, Bilo may be an effective anti-MI agent.

Clear cell renal cell carcinoma (ccRCC) is the most representative subtype of renal cancer, with a highly aggressive phenotype and extremely poor prognosis. Immune escape is one of the main reasons for ccRCC growth and metastasis, in which circular RNAs (circRNAs) play critical roles. Therefore, this research studied circAGAP1-associated mechanisms in immune escape and distant metastasis in ccRCC. circAGAP1/miR-216a-3p/MKNK2 was overexpressed or down-regulated by cell transfection. EdU assay, colony formation assay, scratch assay, Transwell assay, immunoblotting, and flow cytometry were used to evaluate cell proliferation, migration, invasion, EMT, and immune escape, respectively. Dual-luciferase reporting assay and RIP assay were used to evaluate the targeting relationship between circAGAP1/miR-216a-3p/MKNK2. Xenotransplantation in nude mice was used to evaluate the growth of ccRCC tumors in vivo. Here, circAGAP1 high expression was positively correlated with higher histological grade and distant metastasis and was a prognostic indicator for ccRCC. Depleting circAGAP1 effectively hampered the proliferative, invasive, and migratory capacities, EMT, and immune escape of ccRCC cells. Correspondingly, silencing circAGAP1 delayed tumor growth, distant metastasis, and immune escape in vivo. Mechanistically, circAGAP1 sponged the tumor suppressor miR-216a-3p, thereby preventing miR-216a-3p from inhibiting MAPK2. Collectively, our findings demonstrate that circAGAP1 exerts a tumor suppressor function through miR-216a-3p/MKNK2 during the immune escape and distant metastasis in ccRCC, and suggest that circAGAP1 may be a novel prognostic marker and therapeutic target for ccRCC.

Monogenic diabetes caused by GATA6 mutations were almost described as neonatal diabetes, and the phenotypic spectrum has expanded since then. Our study underscores the broad phenotypic spectrum by reporting a de novo GATA6 mutation in a family. Furthermore, we reviewed related literature to summarize the clinical and genetic characteristics of monogenic diabetes with GATA6 mutations (n = 39) in order to improve clinicians' understanding of the disease. We conclude that the GATA6 missense mutation (c. 749G > T, p. Gly250Val) is not reported presently, characterized by adult-onset diabetes with pancreatic dysplasia and located in transcriptional activation region. Carries with GATA6 mutations (n = 55) have a variable spectrum of diabetes, ranging from neonatal (72.7%), childhood-onset (20%) to adults-onset (7.5%). 83.5% of patients with abnormal pancreatic development. Heart and hepatobillary defects are the most common abnormalities of extrapancreatic features. Most mutations with GATA6 are loss of function (LOF, 71.8%) and located in functional region. Functional studies mostly support loss-of-function as the pathophysiological mechanism. In conclusion, there are various types of diabetes with GATA6 mutations, which can also occur in adult diabetes. Phenotypic defects with GATA6 mutations are most frequently malformations of pancreas and heart. This highlights the importance of comprehensive clinical evaluation of identified carriers to evaluate their full phenotypic spectrum.

Pioglitazone (Actos) is one of the most recent oral antidiabetic drugs for treating the second type of diabetes mellitus as a common chronic and lifelong disease, but with harmful side effects. The objective of this study is to evaluate the effectiveness of Artemisia annua L. extract against the Actos drug side effects in the male albino mice. In present study, the use of Actos drug alone induced hepatotoxicity, renal inflammation, hematological disorders and bladder cancer, which are manifested by biochemical abnormalities and histopathological changes, moreover, the severity of toxicity depends on its dose. In contrast, the concurrent treatment with both Actos drug (45 mg/kg) and Artemisia extract (4 g/kg) was effective against the harmful side effects of the Actos drug. Where, the biochemical, hematological and histopathological investigations showed that the hepatotoxicity, renal inflammation, hematological disorders and histopathological changes were improved using combination of Actos and Artemisia extract. In addition, the results of TNF-ɑ oncogene expression levels in bladder tissues were significantly decreased by about 99.99% using the mix of both Actos drug and Artemisia extract. In conclusion, these findings reveal that the Artemisia annua extract on TNF-ɑ oncogene expression level is very significant and effective natural product against harmful side effects of pioglitazone which associated with an increased risk of incident bladder cancer among people, but for application more studies must be achieved in that field.

Efficient healthcare management demands prompt decision-making based on fast diagnostics tools, astute data analysis, and informatics analysis. The rapid detection of analytes at the point of care is ensured using microfluidics in synergy with nanotechnology and biotechnology. The nanobiosensors use nanotechnology for testing, rapid disease diagnosis, monitoring, and management. In essence, nanobiosensors detect biomolecules through bioreceptors by modulating the physicochemical signals generating an optical and electrical signal as an outcome of the binding of a biomolecule with the help of a transducer. The nanobiosensors are sensitive and selective and play a significant role in the early identification of diseases. This article reviews the detection method used with the microfluidics platform for nanobiosensors and illustrates the benefits of combining microfluidics and nanobiosensing techniques by various examples. The fundamental aspects, and their application are discussed to illustrate the advancement in the development of microfluidics-based nanobiosensors and the current trends of these nano-sized sensors for point-of-care diagnosis of various diseases and their function in healthcare monitoring.

This work aimed to assess the Sf9 cell metabolism during growth, and infection steps with recombinant baculovirus bearing rabies virus proteins, to finally obtain rabies VLP in two culture systems: Schott flask (SF) and stirred tank reactor (STR). Eight assays were performed in SF and STR (four assays in each system) using serum-free SF900 III culture medium. Two non-infection growth kinetics assays and six recombinant baculovirus infection assays. The infection runs were carried out at 0.1 pfu/cell multiplicity of infection (MOI) for single baculovirus bearing rabies glycoprotein (BVG) and matrix protein (BVM) and a coinfection with both baculoviruses at MOI of 3 and 2 pfu/cell for BVG and BVM, respectively. The SF assays were done in triplicate. The glucose, glutamine, glutamate, lactate, and ammonium uptake or release specific rates were quantified over the exponential growth phase and infection stage. The highest uptake specific rate was observed for glucose (42.5 × 10-12 mmol cell/h) in SF and for glutamine (30.8 × 10-12 mmol/cell/h) in STR, in the exponential growth phases. A wave pattern was observed for assessed analytes throughout the infection phase and the glucose had the highest wave amplitude within the 10-10 mmol cell/h order. This alternative uptake and release behavior is in harmony with the lytic cycle of baculovirus in insect cells. The virus propagation and VLP generation were not limited by glucose, glutamine, and glutamate, neither by the toxicity of lactate nor ammonium under the conditions appraised in this work. The findings from this work can be useful to set baculovirus infection processes at high cell density to improve rabies VLP yield, purity, and productivity.