The State-of-the-Art Overview to Application of Deep Learning in Accurate Protein Design and Structure Prediction.

In recent years, there has been a notable increase in the scientific community's interest in rational protein design. The prospect of designing an amino acid sequence that can reliably fold into a desired three-dimensional structure and exhibit the intended function is captivating. However, a major challenge in this endeavor lies in accurately predicting the resulting protein structure. The exponential growth of protein databases has fueled the advancement of the field, while newly developed algorithms have pushed the boundaries of what was previously achievable in structure prediction. In particular, using deep learning methods instead of brute force approaches has emerged as a faster and more accurate strategy. These deep-learning techniques leverage the vast amount of data available in protein databases to extract meaningful patterns and predict protein structures with improved precision. In this article, we explore the recent developments in the field of protein structure prediction. We delve into the newly developed methods that leverage deep learning approaches, highlighting their significance and potential for advancing our understanding of protein design.

A comprehensive review of the PTEN/PI3K/Akt axis in multiple myeloma: From molecular interactions to potential therapeutic targets.

Phosphatase and tensin homolog (PTEN), phosphatidylinositol 3-kinase (PI3K), and protein kinase B (Akt) signaling pathways contribute to the development of several cancers, including multiple myeloma (MM). PTEN is a tumor suppressor that influences the PI3K/Akt/mTOR pathway, which in turn impacts vital cellular processes like growth, survival, and treatment resistance. The current study aims to present the role of PTEN and PI3K/Akt/mTOR signaling in the development of MM and its response to treatment. In addition, the molecular interactions in MM that underpin the PI3K/Akt/mTOR pathway and address potential implications for the development of successful treatment plans are also discussed in detail. We investigate their relationship to both upstream and downstream regulators, highlighting new developments in combined therapies that target the PTEN/PI3K/Akt axis to overcome drug resistance, including the use of PI3K and mitogen-activated protein kinase (MAPK) inhibitors. We also emphasize that PTEN/PI3K/Akt pathway elements may be used in MM diagnosis, prognosis, and therapeutic targets.

Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.

BACKGROUND: Solute carrier (SLC) transporters, a diverse family of membrane proteins, are instrumental in orchestrating the intake and efflux of nutrients including amino acids, vitamins, ions, nutrients, etc, across cell membranes. This dynamic process is critical for sustaining the metabolic demands of cancer cells, promoting their survival, proliferation, and adaptation to the tumor microenvironment (TME). Amino acids are fundamental building blocks of cells and play essential roles in protein synthesis, nutrient sensing, and oncogenic signaling pathways. As key transporters of amino acids, SLCs have emerged as crucial players in maintaining cellular amino acid homeostasis, and their dysregulation is implicated in various cancer types. Thus, understanding the intricate connections between amino acids, SLCs, and cancer is pivotal for unraveling novel therapeutic targets and strategies. SCOPE OF REVIEW: In this review, we delve into the significant impact of amino acid carriers of the SLCs family on the growth and progression of cancer and explore the current state of knowledge in this field, shedding light on the molecular mechanisms that underlie these relationships and highlighting potential avenues for future research and clinical interventions. MAJOR CONCLUSIONS: Amino acids transportation by SLCs plays a critical role in tumor progression. However, some studies revealed the tumor suppressor function of SLCs. Although several studies evaluated the function of SLC7A11 and SLC1A5, the role of some SLC proteins in cancer is not studied well. To exert their functions, SLCs mediate metabolic rewiring, regulate the maintenance of redox balance, affect main oncogenic pathways, regulate amino acids bioavailability within the TME, and alter the sensitivity of cancer cells to therapeutics. However, different therapeutic methods that prevent the function of SLCs were able to inhibit tumor progression. This comprehensive review provides insights into a rapidly evolving area of cancer biology by focusing on amino acids and their transporters within the SLC superfamily.

COVID-19 in patients with anemia and haematological malignancies: risk factors, clinical guidelines, and emerging therapeutic approaches.

Extensive research in countries with high sociodemographic indices (SDIs) to date has shown that coronavirus disease 2019 (COVID-19) may be directly associated with more severe outcomes among patients living with haematological disorders and malignancies (HDMs). Because individuals with moderate to severe immunodeficiency are likely to undergo persistent infections, shed virus particles for prolonged periods, and lack an inflammatory or abortive phase, this represents an overall risk of morbidity and mortality from COVID-19. In cases suffering from HDMs, further investigation is needed to achieve a better understanding of triviruses and a group of related variants in patients with anemia and HDMs, as well as their treatment through vaccines, drugs, and other methods. Against this background, the present study aimed to delineate the relationship between HDMs and the novel COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides, effective treatment options for HDM cases were further explored to address this epidemic and its variants. Therefore, learning about how COVID-19 manifests in these patients, along with exploiting the most appropriate treatments, may lead to the development of treatment and care strategies by clinicians and researchers to help patients recover faster. Video Abstract.

Carbon nanotube-wastewater treatment nexus: Where are we heading to?

Water treatment is crucial in solving the rising people's appetite for water and global water shortages. Carbon nanotubes (CNTs) have considerable promise for water treatment because of their adjustable and distinctive arbitrary, physical, as well as chemical characteristics. This illustrates the benefits and risks of integrating CNT into the traditional water treatment resource. Due to their outstanding adsorbent ability and chemical and mechanical properties, CNTs have gained global consideration in environmental applications. The desalination and extraction capability of CNT were improved due to chemical or physical modifications in pure CNTs by various functional groups. The CNT-based composites have many benefits, such as antifouling performance, high selectivity, and increased water permeability. Nevertheless, their full-scale implementations are still constrained by their high costs. Functionalized CNTs and their promising nanocomposites to eliminate contaminants are advised for marketing and extensive water/wastewater treatment.

Epigenetic drugs as new emerging therapeutics: What is the scale's orientation of application and challenges?

Epigenetics is the study of heritable changes in gene expression or function without altering the DNA sequence. Important factors are part of epigenetic events, such as methylation, DNA histone rearrangements, nucleosome transposition, and non-coding RNAs. Dysregulated epigenetic mechanics are associated with various cancers' initiation, development, and metastasis. It is known that the occurrence and development of cancer can be controlled by regulating unexpected epigenetic events. Epi-drugs are used singly or in combination with chemotherapy and enhance antitumor activity, reduce drug resistance, and stimulate the host immune response. Despite these benefits, epigenetic therapy as a single therapy or in combination with other drugs leads to adverse effects. This review article introduces and compares the advantages, disadvantages, and side effects of using these drugs for the first time since their introduction. Also, this article describes the mechanism of action of various epigenetic drugs. Recommendations for future use of epigenetic drugs as cancer therapeutics are suggested as an overall conclusion.

Therapeutic targeting of the tumor microenvironments with cannabinoids and their analogs: Update on clinical trials.

Cancer is a major global public health concern that affects both industrialized and developing nations. Current cancer chemotherapeutic options are limited by side effects, but plant-derived alternatives and their derivatives offer the possibilities of enhanced treatment response and reduced side effects. A plethora of recently published articles have focused on treatments based on cannabinoids and cannabinoid analogs and reported that they positively affect healthy cell growth and reverse cancer-related abnormalities by targeting aberrant tumor microenvironments (TMEs), lowering tumorigenesis, preventing metastasis, and/or boosting the effectiveness of chemotherapy and radiotherapy. Furthermore, TME modulating systems are receiving much interest in the cancer immunotherapy field because it has been shown that TMEs have significant impacts on tumor progression, angiogenesis, invasion, migration, epithelial to mesenchymal transition, metastasis and development of drug resistance. Here, we have reviewed the effective role of cannabinoids, their analogs and cannabinoid nano formulations on the cellular components of TME (endothelial cells, pericytes, fibroblast and immune cells) and how efficiently it retards the progression of carcinogenesis is discussed. The article summarizes the existing research on the molecular mechanisms of cannabinoids regulation of the TME and finally highlights the human studies on cannabinoids' active interventional clinical trials. The conclusion outlines the need for future research involving clinical trials of cannabinoids to demonstrate their efficacy and activity as a treatment/prevention for various types of human malignancies.

Cellular and molecular basis of therapeutic approaches to breast cancer.

In recent decades, there has been a significant amount of research into breast cancer, with some important breakthroughs in the treatment of both primary and metastatic breast cancers. It's a well-known fact that treating breast cancer is still a challenging endeavour even though physicians have a fantastic toolset of the latest treatment options at their disposal. Due to limitations of current clinical treatment options, traditional chemotherapeutic drugs, and surgical options are still required to address this condition. In recent years, there have been several developments resulting in a wide range of treatment options. This review article discusses the cellular and molecular foundation of chemotherapeutic drugs, endocrine system-based treatments, biological therapies, gene therapy, and innovative techniques for treating breast cancer.

Bacterial Microleakage at the Implant-Abutment Interface: An In Vitro Study.

The objective of this study is to evaluate, in vitro, the microleakage of bacteria of 3 different implant connections for a period of 14 days. 60 dental implants (AoN) (n = 20) were distinguished into three groups, accordingly to the type of connection: External Hexagon (EH), Internal Hexagon (IH), and Cone Morse (CM) connection. All implants were inserted and fixed on sterile special vinyl support. Ten fixtures for each group were inoculated in the internal platform with 1.0 µL of Streptococcus oralis (SO) and the other ten with the same amount of Pseudomonas aeruginosa (PA). The penetration of bacterial suspension into the surrounding solution was determined by the observation of the turbidity of the broth. Five implants for each sub-group were randomly observed at SEM, to verify the correct fitting of the abutments. Considering the total of the samples analyzed, CM showed significantly lower bacterial contamination, with respect to IH. In particular, bacterial contamination was found in 45%, 55%, and 20% of EH, IH, and CM, respectively. Analyzing results for the type of inoculated bacteria, P. aeruginosa showed a higher ability to contaminate all the connections, with respect to S. oralis.

Mechanical Characteristics of Cement Paste in the Presence of Carbon Nanotubes and Silica Oxide Nanoparticles: An Experimental Study.

Considering the remarkable characteristics of nanomaterials, previous research studies investigated the effects of incorporating different types of these materials on improving the concrete properties. However, further studies are required to evaluate the complementary hybridization and synergistic influence of nanomaterials. In this research, the combined effect of adding nano silica particles (NS) and multi-walled carbon nanotubes (MWCNT) on enhancing both the compressive and flexural strengths of the cement paste was investigated. Moreover, the morphology of the interface between cement paste and aggregates was studied by scanning electron microscopy (SEM). The mixtures were prepared using three different portions of MWCNT and NS. Electron microscopy images indicated a uniform distribution of nanoparticles in the cement matrix, enhanced hydration reactions, and increased density. Based on the experiments' outcomes, the combined utilization of silica and carbon nanomaterials in the cement paste did not necessarily result in the maximum compressive and flexural strengths. Furthermore, it was observed that the use of higher percentages of pristine NS in the absence of MWCNT can lead to further enhancement of strength properties of the cement paste.