Current pharmaceutical biotechnology最新文献

Aims: This study aims to comprehensively investigate the role of Family Member A with sequence similarity 72-A (FAM72A) in multiple myeloma.

Background: Multiple myeloma poses significant challenges. This study delves into FAM72A's impact on key cellular processes, shedding light on potential therapeutic targets and enhancing our understanding of multiple myeloma progression.

Objective: Investigate the impact of FAM72A on the proliferation, apoptosis, and bortezomib sensitivity of multiple myeloma cell line U266.

Methods: qRT-PCR analyzed FAM72A expression levels in bone marrow samples from 30 patients with multiple myeloma and 10 healthy donors at the Second Hospital of Shanxi Medical University. Cell lines overexpressing FAM72A were constructed, and Cell Counting Kit 8 (CCK-8) and flow cytometry were used to assess U266 cell proliferation, apoptosis, and sensitivity to bortezomib. Biological predictions for FAM72A were performed to find transcription factors binding to the FAM72A promoter region, verified using a luciferase assay. U266 cells were transfected with si-POU2F2 (POU class 2 homeobox 2), and the impact on cell proliferation was validated. Western blot analysis detected the expression of downstream proteins in the p53 signaling pathway. In vivo, experiments established a xenograft mouse model further to study the role of FAM72A in multiple myeloma.

Results: FAM72A was upregulated in multiple myeloma bone marrow tissues. Compared to the OE-NC group, the OE-FAM72A group showed increased Mouse Double Minute 2 homolog (MDM2) expression, decreased p53 expression, increased cell proliferation, and decreased apoptosis. POU2F2 was identified as the upstream transcription factor for FAM72A. Compared to the si-NC group, the si-POU2F2 group exhibited decreased MDM2 expression, increased p53 expression, slowed cell proliferation, and increased apoptosis. Silencing POU2F2 could reverse the pro-proliferative effect of over-expressing FAM72A in U266 cells. In vivo experiments in a xenograft mouse model further studied the role of FAM72A in multiple myeloma.

Conclusion: Overexpression of FAM72A promotes U266 cell proliferation, inhibits apoptosis, and reduces sensitivity to bortezomib by regulating the POU2F2/FAM72A/p53 signaling pathway.

Immunoglobulins (Ig) are proteins that help fight infections. IgG (IgG1, IgG2, IgG3, IgG4), IgM, IgA, IgD, and IgE are the five immunoglobulin subtypes that make up the majority of our immune system. Beneficial effects have been observed on the administration of Ig in diseases like Kawasaki, multiple myositis, chronic inflammatory demyelinating polyneuropathy (CIDP), and immune thrombocytopenia purpura (ITP). The Fc region, FcγRs, and FcRn of the IgG interact to provide both pro- and anti-inflammatory effects. IgM blocks immune-mediated inflammation using N-like glycans. It has been demonstrated that IgM demonstrates its antiinflammatory activity through IgM anti-leukocyte auto-antibodies (IgM-ALA). Since IgA is the second most prevalent and important Ig that operates on the primary objective in the immune system, which exhibits inhibitory signals in the body and generates inflammation in host cells, it plays a critical role in controlling mucosal homeostasis in the gastrointestinal (GI) tract. Additionally, it has been discovered that activating FcαRI boosts cytokine responses at different levels. IgD, a mysterious class of Ig once discovered, has a role in many disorders, including myeloma and Hodgkin's disease. The stability of IgD with development shows a different role, which has an advantage for the host's survival. IgE is mainly associated with many allergic diseases (food allergies), mediates type 1 responses, and has defenses against parasitic infections, which makes it an important parameter for monoclonal antibodies. Studies showed the possible roles of immunoglobulins, from which it came to light that immunoglobulins have their functions as agonists and antagonists in inflammation.

The truancy of representation of the estrogen, progesterone, and human epidermal growth factor receptors occurs during TNBC. TNBC is recognized for the upper reappearance and has a poorer diagnosis compared with rest breast cancer (BC) types. Presently, as such, no targeted therapy is approved for TNBC and treatment options are subjected to chemotherapy and surgery, which have high mortality rates. Hence, the current article focuses on the scenario of TNBC vital pathways and discusses the latest advances in TNBC treatment, including immune checkpoint inhibitors (ICIs), PARP suppressors, and cancer vaccines. Immunotherapy and ICIs, like PD 1 and PD L1 suppressors, displayed potential in clinical trials (CTs). These suppressors obstruct the mechanisms which allow tumor cells to evade the system thereby boosting the body's defense against TNBC. Immunotherapy, either alone or combined with chemotherapy has demonstrated patient outcomes such as increased survival rates and reduced treatment-related side effects. Additionally, targeted therapy approaches include BRCA/2 mutation poly ribose polymerase inhibitors, Vascular Endothelial Growth Factor Receptor (VEGFR) inhibitors, Epidermal growth factor receptor inhibitors, Fibroblast growth factor inhibitors, Androgen Receptor inhibitors, PIK3/AKT/mTOR pathway inhibitors, Cyclin-dependent kinase (CDK) inhibitors, Notch signaling pathway inhibitors, Signal transducer and activator of transcription 3 (STAT3) signaling pathway inhibitors, Chimeric antigen receptor T (CAR-T) cell therapy, Transforming growth factor (TGF) -β inhibitors, Epigenetic modifications (EPM), Aurora Kinase inhibitors and antibody-drug conjugates. We also highlight ongoing clinical trials and potential future directions for TNBC therapy. Despite the challenges in treating TNBC, recent developments in understanding the molecular and immune characteristics of TNBC have opened up new opportunities for targeted therapies, which hold promise for improving outcomes in this aggressive disease.

Skin cancer, a global burden for particularly white people, is classified as various histopathological types, including malignant melanoma, basal and squamous cell carcinoma, on the basis of affected different skin layers. Clinical adjuvant therapy (electro-chemotherapy, radio- and immuno therapy), surgical techniques (Cryosurgery, laser treatment, dermabrasion, Moh's micrographic surgery), photodynamic treatment and theranostic approaches are confined only for the treatment of serious health issues. Therefore, nanotechnology based approaches, especially nanoemulsion, a non-spontaneous, transparent or translucent, kinetically stable nanostructured (1-1000nm) colloidal dispersion (comprised of oil, water and surfactant/cosurfactant), are being popularised as a potential topical nanocarrier to deliver BCS class II and IV anti-neoplastic drugs attributing to its capacity for both active and passive tumor targeting in controlled or sustained manner and improving bioavailability via enhancing permeabilityretention effect with minimal adverse effects. Numerous research on nanoemulsion for the treatment of both melanoma and non-melanoma skin cancer is only limited to preclinical stages as several physiological variables reduce the effectiveness of nanoemulsion via restricting topical penetration.

As the world recovers from the COVID-19 pandemic, a resurgence in MPXV cases is causing serious concern. The early clinical similarity of MPXV to common ailments like the flu and cold, coupled with the resemblances of its progressing rash to other infections, underscores the importance of prompt and accurate diagnosis. Among the infections, smallpox is clinically closest to MPXV, and rashes similar to MPXV stages also appear in syphilis and varicella zoster. A comprehensive review of MPXV, herpes, and syphilis was carried out, including structural and morphological features, origins, transmission modes, and computational studies. PubMed literature search on MPXV, using MeSH key terms, yielded 1904 results, with the analysis revealing prominent links to sexually transmitted diseases. More in-depth exploration of MPXV, Herpes Simplex Virus (HSV), and Syphilis revealed further disease interconnections and geographical correlations. These findings emphasize the need for a holistic understanding of these interconnected infectious agents for better control and management.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease that falls underthe umbrella of dementia and is characterized by the presence of enormously neurotoxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) of tau protein inside the brain. ADremains an intractable global health challenge with limited therapeutic options. Early diagnosis,enabled by biomarkers and neuroimaging, is pivotal for optimizing treatment outcomes. Immunotherapeuticstrategies, including monoclonal antibodies, active vaccination, and passive immunization,have been developed to target hallmark AD pathology, such as amyloid-beta aggregation.Here we summarized the emerging role of immunotherapies in the early stages of AD,shedding light on recent breakthroughs and clinical progress. Challenges, including treatmentresponse variability and safety concerns, are discussed alongside evolving approaches, such aspersonalized immunotherapy and combinatorial treatments. This concise review underscores thepromise of immunotherapies as a transformative approach to AD intervention, offering hope fora brighter future in the quest to combat this devastating neurodegenerative disease.

Skin cancer is one of the most common and complex types of the disease, resulting in a high mortality rate worldwide. Skin cancer can be treated with chemotherapy, surgery, radiotherapy, etc. In most cases, a patient's condition and the type of skin cancer determine the recommended treatment options. As a result of poor penetration of the drug into stratum corneum or lesions, low efficacy, and higher concentrations of active pharmaceutical ingredients required to achieve a therapeutic effect, the efficacy of skin cancer therapy has been limited. The high dose requirement, as well as poor bioavailability at the site of action, causes skin inflammation, which greatly hinders drug absorption. This review mainly focuses on research on nanocarriers for sitespecific and controlled delivery of therapeutics for skin cancer treatment. The information related to various nanocarriers systems for skin cancer will be illustrated. This also focused on patents, clinical trials, and research carried out in the field of liposomes, niosomes, ethosomes, nanoparticles, microemulsion, nanoemulsions, gels, nanogels, hydrogels, dendrimers, and nanofibers for treating skin cancer. Nanotechnology-based therapy has shown great promise in controlling skin cancer and can be used to deliver drugs more effectively.

In the current scenario, obesity is a stimulating health problem and is growing very rapidly in the world. It is a complex disease caused by the imbalance between the energy intake and the energy expenditure. There are various diseases associated with obesity, i.e., diabetes, hypertension, cancer, atherosclerosis, and other cardiovascular problems, which produce a serious impact on the social and financial system of the population. Moreover, changing the lifestyle and other behavioral changes might help in decreasing weight loss, but it is quite challenging to achieve. Nearly 10-20% of males and 20-30% of females come under the obese condition. The most convenient therapy for treating obesity is the use of synthetic drugs available in the markets, like orlistat and sibutramine, but these drugs have serious side effects, along with this surgical procedure, and are also not safe. Various herbal medicines and bioactives are preferred as game changers. Many herbal plants and their bioactive compounds have recently demonstrated promising effects in treating obesity. They achieve this by acting on various signaling pathways, reducing the levels of hormones associated with obesity, and regulating the abundance and composition of gut microbiota. This review concludes by highlighting the potential role of various herbal plants in managing obesity.

Background: Tyrosinase, often recognized as polyphenol oxidase, plays a pivotal role as an enzyme in catalyzing the formation of melanin-a complex process involving the oxidation of monophenols and o-diphenols.

Objective: Tyrosinase functions as a monooxygenase, facilitating the o-hydroxylation of monophenols to generate the corresponding catechols, as well as catalyzing the oxidation of monophenols to form the corresponding o-quinones, exhibiting diphenolase or catecholase activity. This versatile enzymatic capability is not limited to specific organisms but is found across various sources, including bacteria, fungi, plants, and mammals.

Method: Pertinent research articles, reviews, and patents on tyrosinase were gathered through a comprehensive literature search. These materials were analyzed to gain insights into the diverse applications of tyrosinase. The review was structured by categorizing these applications and offering a thorough summary of the current state of knowledge in the field.

Result: Based on the literature survey, tyrosinase exhibits promising potential across a spectrum of biotechnological applications. These include but are not limited to: synthesizing L-DOPA, creating innovative mixed melanins, manufacturing phenolic biosensors, deploying in food and feed industries, facilitating protein cross-linking, eliminating phenols and dyes, and serving as a biocatalyst. Moreover, immobilized tyrosinase demonstrates multiple utility avenues within the pharmaceutical sector.

Conclusion: The article offers a comprehensive exploration of tyrosinase, encompassing its structural features, evolutionary origins, biochemical characteristics, and contemporary applications in various fields.

Cancer is one of the main reasons for death, and it threatens human life and health. Both the environment and genes can lead to cancers. It dates back more than a million years; more importantly, tumor cells can not be detected until they grow to a large number. Currently, cancers are treated with surgical excision or non-surgical procedures. By studying the interaction between ncRNAs and PKM2, we aim to provide new targets for diagnosis, treatment, and prognosis for cancers. Read relevant articles and made a summary and classification. Non-coding RNAs (ncRNAs) are RNAs that do not code for proteins. They perform a function in transcription and translation and can be used as targets for cancer therapy. Pyruvate kinase M2 (PKM2) is a form of PKM, and it catalyzes the glycolysis of the final cellular processes to promote tumorigenesis. Not only that, but it also plays non-metabolic functions, including the expression of the gene, cell proliferation, cell migration, and tumor angiogenesis in cancer cells. The existing studies have found that microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) can promote or inhibit the aerobic glycolysis of cancer cells by affecting PKM2, which increases or decrease the risk of cancers and affect the progression of cancers. This review focuses on the mechanism of ncRNAs regulating PKM2 in cancers and summarizes the roles of some ncRNAs.