Application of ChatGPT for Orthopedic Surgeries and Patient Care.

Artificial intelligence (AI) has rapidly transformed various aspects of life, and the launch of the chatbot "ChatGPT" by OpenAI in November 2022 has garnered significant attention and user appreciation. ChatGPT utilizes natural language processing based on a "generative pre-trained transfer" (GPT) model, specifically the transformer architecture, to generate human-like responses to a wide range of questions and topics. Equipped with approximately 57 billion words and 175 billion parameters from online data, ChatGPT has potential applications in medicine and orthopedics. One of its key strengths is its personalized, easy-to-understand, and adaptive response, which allows it to learn continuously through user interaction. This article discusses how AI, especially ChatGPT, presents numerous opportunities in orthopedics, ranging from preoperative planning and surgical techniques to patient education and medical support. Although ChatGPT's user-friendly responses and adaptive capabilities are laudable, its limitations, including biased responses and ethical concerns, necessitate its cautious and responsible use. Surgeons and healthcare providers should leverage the strengths of the ChatGPT while recognizing its current limitations and verifying critical information through independent research and expert opinions. As AI technology continues to evolve, ChatGPT may become a valuable tool in orthopedic education and patient care, leading to improved outcomes and efficiency in healthcare delivery. The integration of AI into orthopedics offers substantial benefits but requires careful consideration and continuous improvement.

A Molecular Perspective on HIF-1α and Angiogenic Stimulator Networks and Their Role in Solid Tumors: An Update.

Hypoxia-inducible factor-1α (HIF-1α) is a major transcriptional factor, which plays an important role in cellular reprogramming processes under hypoxic conditions, which facilitate solid tumors' progression. HIF-1α is directly involved in the regulation of the angiogenesis, metabolic reprogramming, and extracellular matrix remodeling of the tumor microenvironment. Therefore, an in-depth study on the role of HIF-1α in solid tumor malignancies is required to develop novel anti-cancer therapeutics. HIF-1α also plays a critical role in regulating growth factors, such as the vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor, in a network manner. Additionally, it plays a significant role in tumor progression and chemotherapy resistance by regulating a variety of angiogenic factors, including angiopoietin 1 and angiopoietin 2, matrix metalloproteinase, and erythropoietin, along with energy pathways. Therefore, this review attempts to provide comprehensive insight into the role of HIF-1α in the energy and angiogenesis pathways of solid tumors.

Hypoxia-Inducible Factor and Oxidative Stress in Tendon Degeneration: A Molecular Perspective.

Tendinopathy is a debilitating condition marked by degenerative changes in the tendons. Its complex pathophysiology involves intrinsic, extrinsic, and physiological factors. While its intrinsic and extrinsic factors have been extensively studied, the role of physiological factors, such as hypoxia and oxidative stress, remains largely unexplored. This review article delves into the contribution of hypoxia-associated genes and oxidative-stress-related factors to tendon degeneration, offering insights into potential therapeutic strategies. The unique aspect of this study lies in its pathway-based evidence, which sheds light on how these factors can be targeted to enhance overall tendon health.

Computational Analysis of miR-140 and miR-135 as Potential Targets to Develop Combinatorial Therapeutics for Degenerative Tendinopathy.

Background: Degenerative tendinopathy, a condition causing movement restriction due to high pain, highly impacts productivity and quality of life. The healing process is a complex phenomenon and involves a series of intra-cellular and inter-cellular processes. Proliferation and differentiation of the tenocyte is a major and essential process to heal degenerative tendinopathy. The recent development in microRNA (miRNA)-mediated reprogramming of the cellular function through specific pathways opened door for the development of new regenerative therapeutics. Based on information about gene expression and regulation of tendon injury and healing, we attempted to evaluate the combinatorial effect of selected miRNAs for better healing of degenerative tendinopathy. Methods: The present study was designed to evaluate the combinatorial effect of two miRNAs (has-miR-140 and has-miR-135) in the healing process of the tendon. Publicly available information/data were retrieved from appropriate platforms such as PubMed. Only molecular data, directly associated with tendinopathies, including genes/proteins and miRNAs, were used in this study. The miRNAs involved in tendinopathy were analyzed by a Bioinformatics tools (e.g., TargetScan, miRDB, and the RNA22v2). Interactive involvement of the miRNAs with key proteins involved in tendinopathy was predicted by the Insilco approach. Results: Based on information available in the public domain, tendon healing-associated miRNAs were predicted to explore their therapeutic potentials. Based on computation analysis, focusing on the potential regulatory effect on tendon healing, the miR-135 and miR-140 were selected for this study. These miRNAs were found as key players in tendon healing through Rho-associated coiled-coil containing protein kinase 1 (ROCK1), IGF-1/PI3K/Akt, PIN, and Wnt signaling pathways. It was also predicted that these miRNAs may reprogram the cells to induce proliferation and differentiation activity. Many miRNAs are likely to regulate genes important for the tendinopathy healing process, and the result of this study allows an approach for miRNA-mediated regeneration of the tenocyte for tendon healing. Based on computational analysis, the role of these miRNAs in different pathways was established, and the results provided insights into the combinatorial approach of miRNA-mediated cell reprogramming. Conclusions: In this study, the association between miRNAs and the disease was evaluated to correlate the tendinopathy genes and the relevant role of different miRNAs in their regulation. Through this study, it was established that the synergistic effect of more than one miRNA on directed reprogramming of the cell could be helpful in the regeneration of damaged tissue. It is anticipated that this study will be helpful for the design of miRNA cocktails for the orchestration of cellular reprogramming events.

Polybrominated diphenyl ethers in the environment: a wake-up call for concerted action in India.

Polybrominated diphenyl ethers (PBDEs) are a class of persistent organic pollutants (POPs) used as flame retardants in the products utilized in day-to-day life. Their bioaccumulation, low volatility, and high persistence in the environment have led to their global spread even to remote and distant regions. The present study identifies gaps in the investigation of the neurotoxic potential of PBDEs, their effects on brain development, toxicokinetic, and their potential as a carcinogen. In India, to date, only human breast milk was assessed for levels of PBDEs, and it is suggested that other human tissues can also be explored. No data on the reproductive toxicity of PBDEs are reported from Indian cohorts. Long-range transport and deposition of PBDEs in colder regions necessitates monitoring of Himalayan regions in India. An inventory of PBDEs is required to be made for addressing the worrisome situation of the unregulated import of E-waste from the developed countries in India. The study also emphasizes providing guidelines for the articulation of policies regarding sound surveillance and management of PBDE production, consumption, and release in the Indian context. It is recommended that a separate cell for monitoring and follow-up of PBDEs should be established in India. Also, the development of better alternatives and environment-friendly remediation technologies for PBDEs is the need of the hour.

Aspergillus niger whole-cell catalyzed synthesis of caffeic acid phenethyl ester in ionic liquids.

Synthesis of caffeic acid ester essentially requires an efficient esterification process to produce various kinds of medicinally important ester derivatives. In the present study, a comprehensive and comparative analysis of whole-cell catalyzed caffeic acid esters production in ionic liquids (ILs) media was performed. Olive oil induced mycelial mass of halotolerant Aspergillus niger (A.niger) EXF 4321 was freeze dried and used as a catalyst. To ensure maximum solubilization of caffeic acid for highest substrate loading several ILs were screened and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([Emim][Tf2N]) was found to have the maximum solubility and favoured for enzymatic activity of freeze dried mycelia. The whole-cell catalyzed synthesis of caffeic acid phenethyl ester (CAPE) conditions were optimized and bioconversion up to 84% was achieved at a substrate molar ratio of 1:20 (caffeic acid:2-phenyl ethanol), 30°C for 12h. Results obtained during this study were encouraging and helpful to design a bioreactor system to produce caffeic acid derived esters.

Ionic liquids as novel solvents for the synthesis of sugar fatty acid ester.

Sugar fatty acid esters are bio-surfactants known for their non-toxic, non-ionic, and high biodegradability . With great emulsifying and conditioning effects, sugar fatty acids are widely used in the food, pharmaceutical, and cosmetic industries. Biosynthesis of sugar fatty acid esters has attracted growing attention in recent decades. In this study, the enzymatic synthesis of sugar fatty acid esters in ionic liquids was developed, optimized, and scaled up. Reaction parameters affecting the conversion yield of lipase-catalyzed synthesis of glucose laurate from glucose and vinyl laurate (i.e. temperature, vinyl laurate/glucose molar ratio, and enzyme loads) were optimized by response surface methodology (RSM). In addition, production was scaled up to 2.5 L, and recycling of enzyme and ionic liquids was investigated. The results showed that under optimal reaction conditions (66.86 °C, vinyl laurate/glucose molar ratio of 7.63, enzyme load of 73.33 g/L), an experimental conversion yield of 96.4% was obtained which is close to the optimal value predicted by RSM (97.16%). A similar conversion yield was maintained when the reaction was carried out at 2.5 L. Moreover, the enzymes and ionic liquids could be recycled and reused effectively for up to 10 cycles. The results indicate the feasibility of ionic liquids as novel solvents for the biosynthesis of sugar fatty acid esters.

In silico characterization of alkaline proteases from different species of Aspergillus.

A total of 49 protein sequences of alkaline proteases retrieved from GenBank representing different species of Aspergillus have been characterized for various physiochemical properties, homology search, multiple sequence alignment, motif, and super family search and phylogenetic tree construction. The sequence level homology was obtained among different groups of alkaline protease enzymes, viz alkaline serine protease, oryzin, calpain-like protease, serine protease, subtilisin-like alkaline proteases. Multiple sequence alignment of alkaline protease protein sequence of different Aspergillus species revealed a stretch of conserved region for amino acid residues from 69 to 110 and 130-204. The phylogenetic tree constructed indicated several Aspergillus species-specific clusters for alkaline proteases namely Aspergillus fumigatus, Aspergillus niger, Aspergillus oryzae, Aspergillus clavatus. The distributions of ten commonly observed motifs were analyzed among these proteases. Motif 1 with a signature amino acid sequence of 50 amino acids, i.e., ASFSNYGKVVDIFAPGQDILSCWIGSTTATNTISGTSMATPHIVGLSCYL, was uniformly observed in proteases protein sequences indicating its involvement with the structure and enzymatic function. Motif analysis of acidic proteases of Aspergillus and bacterial alkaline proteases has revealed different signature amino acid sequences. The superfamily search for these proteases revealed the presence of subtilases, serine-carboxyl proteinase, calpain large subunit, and thermolysin-like superfamilies with 45 representing the subtilases superfamily.