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Развитие микробиотерапии: роль синтетической биологии в инженерных микробных сообществах для точной медицины.

В последние годы исследования в области микробиотических исследований и синтетической биологии были посвящены изучению новых подходов к микробным манипуляциям в терапевтических целях. Тем не менее, по этому аспекту имеется фрагментированная информация с ключевыми идеями, разбросанными по различным дисциплинам, таким, как молекулярная биология, генетика, биоинженерия и медицина. Цель этого обзора заключается в создании преобразующего потенциала синтетической биологии в плане развития исследований и лечения микробиоме, что имеет значительные последствия для здравоохранения, сельского хозяйства и

COVID-19 and Cancer Comorbidity: Therapeutic Opportunities and Challenges.

The coronavirus disease 2019 (COVID-19) is a viral disease caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that affects the respiratory system of infected individuals. COVID-19 spreads between humans through respiratory droplets produced when an infected person coughs or sneezes. The COVID-19 outbreak originated in Wuhan, China at the end of 2019. As of 29 Sept 2020, over 235 countries, areas or territories across the globe reported a total of 33,441,919 confirmed cases, and 1,003,497 confirmed deaths due to COVID-19. Individuals of all ages are at risk for infec

Targeting FGFR for cancer therapy.

The FGFR signaling pathway is integral to cellular activities, including proliferation, differentiation, and survival. Dysregulation of this pathway is implicated in numerous human cancers, positioning FGFR as a prominent therapeutic target. Here, we conduct a comprehensive review of the function, signaling pathways and abnormal alterations of FGFR, as well as its role in tumorigenesis and development. Additionally, we provide an in-depth analysis of pivotal phase 2 and 3 clinical trials evaluating the performance and safety of FGFR inhibitors in oncology, thereby shedding light on the current

Микроглиа регулирует расчистку миелин и метаболизм холестерина после демиелинации с помощью интерферона регулирующего коэффициента 5.

Регулирующий фактор интерферона 5 (IRF5) — это фактор транскрипции, который играет определенную роль в организации врожденной иммунной реакции, особенно в ответ на вирусные инфекции. В частности, IRF5 был определен как ген микроглийного риска, связанный с множественным склерозом (MS), однако его конкретная роль в патогенезе MS остается неясной. С помощью ирф5-/- мышей наше исследование обнаруживает неканоническую функцию IRF5 в восстановлении MS. Ирф5-/- мыши продемонстрировали повышенный ущерб в экспериментальной модели аутоиммунной энцефаломиелита (EAE) и продемонстрировали неисправный набор

NAD+‒circadian rhythm coupling in dementia.

The circadian rhythm system and sleep coordinate whole-body functions across the 24-h cycle, yet these rhythms progressively deteriorate with neurodegenerative diseases, including dementia. Growing evidence indicates that nicotinamide adenine dinucleotide (NAD+) interacts with the circadian system through multiple molecular pathways and that NAD+ levels decline with dementia. In this review, we synthesize current evidence on the bidirectional relationship between NAD+ metabolism and circadian regulation in several dementia disorders, emphasizing the key circadian pathways, the nicotinamide pho

SUBJECT INDEX Volume 125 (JANUARY–JUNE, 2004)

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Role of phytoconstituents in the management of COVID-19.

BackgroundCOVID-19, a severe global pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has emerged as one of the most threatening transmissible disease. As a great threat to global public health, the development of treatment options has become vital, and a rush to find a cure has mobilized researchers globally from all areas.Scope and approachThis review focuses on deciphering the potential of different secondary metabolites from medicinal plants as therapeutic options either as inhibitors of therapeutic targets of SARS-CoV-2 or as blockers of viral particles entry

The effect of growth hormone on ovarian function recovery in a mouse model of ovarian insufficiency.

ObjectivesTo evaluate the effects and mechanisms of action of growth hormone (GH) in the recovery of ovarian function in ovarian insufficiency induced by cyclophosphamide (CP) in a mouse model.Materials and methodsAfter inducing ovarian insufficiency by administering 400 mg/kg of CP intraperitoneally to 6-week-old ICR mice, the mice were divided into four groups (control, CP, 1 mg/kg GH, and 2 mg/kg GH) with 10 mice in each group. GH was administered a week later for 7 days. Five mice from each group were sacrificed the next day, and their ovaries were collected for histological examination. T

CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool.

Bacteriophages are pervasive viruses that infect bacteria, relying on their genetic machinery to replicate. In order to protect themselves from this kind of invader, bacteria developed an ingenious adaptive defence system, clustered regularly interspaced short palindromic repeats (CRISPR). Researchers soon realised that a specific type of CRISPR system, CRISPR-Cas9, could be modified into a simple and efficient genetic engineering technology, with several improvements over currently used systems. This discovery set in motion a revolution in genetics, with new and improved CRISPR systems being

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies.

Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system's monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells' evasion of the immune system and p

Совпадение в полном тексте источника
… The biogenesis of miRNAs initiates with the transcription of dedicated information units by RNA polymerase II, progressing through successive maturation steps to produce the final functional regulators ( Treiber et al., 2019 ). … This transcription is predominantly executed by RNA polymerase II ( Schier and Taatjes, 2020 ), although certain virus-encoded miRNAs are transcribed by RNA polymerase III ( Nanbo et al., 2021 ). …

Candidate Regulatory Relationship and Expression Correlation Between miR-33a-5p and ANK3 in Chronic Myeloid Leukemia.

Chronic myeloid leukemia (CML) is a type of bone marrow cancer characterized by the uncontrolled proliferation of myeloid cells. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a crucial role in the post-transcriptional regulation of gene expression. This study aims to examine the association between miR-33a-5p and Ankyrin 3 (ANK3) in CML and to investigate the regulatory mechanisms of miR-33a-5p in the progression of this disease. mRNA expression profiles were obtained from the GSE100026 dataset within the Gene Expression Omnibus (GEO) repository. Quantitative real-time polym

Совпадение в полном тексте источника
… For Molecular Functions (MFs), the results indicated that these genes were primarily i n volved in processes including disordered domain-specific binding, transmembrane transporter binding, and RNA polymerase II-specific DNA-binding transcription factor binding ( Table 1 ). …

Therapeutic Advances in Oncology.

Around 77 new oncology drugs were approved by the FDA in the past five years; however, most cancers remain untreated. Small molecules and antibodies are dominant therapeutic modalities in oncology. Antibody-drug conjugates, bispecific antibodies, peptides, cell, and gene-therapies are emerging to address the unmet patient need. Advancement in the discovery and development platforms, identification of novel targets, and emergence of new technologies have greatly expanded the treatment options for patients. Here, we provide an overview of various therapeutic modalities and the current treatment

Anti-Cancer Research Progress of Triptolide: Mechanisms of Action, Structural Modifications, Nanodelivery Systems and Clinical Challenges.

Triptolide is a bioactive diterpenoid lactone from traditional Chinese medicine with notable anti-tumor, immunosuppressive, and anti-inflammatory properties. However, its clinical utility is hampered by poor solubility, a narrow therapeutic index, and multi-organ toxicity. In response, extensive efforts have been made to improve its efficacy and safety profile. This review critically examines recent progress in Triptolide research, covering its mechanisms of action, derivative design, drug delivery systems, and cancer-specific applications. It also evaluates its clinical potential against panc

Совпадение в полном тексте источника
… XPB is the DNA helicase subunit of the transcription factor IIH (TFIIH) complex, which regulates transcription initiation by RNA polymerase II (Pol II) and is essential for nucleotide excision repair (NER). 26 Triptolide irreversibly inhibits the ATPase activity of XPB through covalent binding, which … subsequently triggers phosphorylation and ubiquitination of the largest subunit of RNA polymerase II, Rpb1, ultimately leading to its degradation. 27,28 This cascade of events results in global suppression of both gene transcription and NER, with short-lived oncoproteins (such as c-Myc) and cyclins …

Exome sequencing identifies germline variants in DIS3 in familial multiple myeloma.

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Совпадение в полном тексте источника
… Szczepińska T Kalisiak K Tomecki R Labno A Borowski LS Kulinski TM DIS3 shapes the RNA polymerase II transcriptome in humans by degrading a variety of unwanted transcripts Genome Res 2015 25 1622 33 10.1101/gr.189597.115 26294688 PMC4617959 …

Epigenetic regulation in hematopoiesis and its implications in the targeted therapy of hematologic malignancies.

Hematologic malignancies are one of the most common cancers, and the incidence has been rising in recent decades. The clinical and molecular features of hematologic malignancies are highly heterogenous, and some hematologic malignancies are incurable, challenging the treatment, and prognosis of the patients. However, hematopoiesis and oncogenesis of hematologic malignancies are profoundly affected by epigenetic regulation. Studies have found that methylation-related mutations, abnormal methylation profiles of DNA, and abnormal histone deacetylase expression are recurrent in leukemia and lympho

Совпадение в полном тексте источника
… RNA polymerase II (Pol II) first transcribes miRNA-encoding genes in the nucleus, producing a lengthy primary transcript called pri-miRNA. …

Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.

BACKGROUND: Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. AIMS/OBJECTIVES: This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and o

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… Flavopiridol, a synthetic compound structurally similar to rohitukine from the Indian plant Dysoxylum binectariferum [ 59 ], targets cyclin-dependent kinases, including the cyclin T/CDK9 complex, inactivates p-TEFb and blocks most RNA polymerase II transcription, and also suppresses anti-apoptotic proteins …

Solamargine induces autophagy-mediated apoptosis and enhances bortezomib activity in multiple myeloma.

Multiple myeloma (MM) is an incurable plasma cell malignancy with a poor survival rate. Conventional chemotherapeutic agent-induced adverse events, including toxicity, neuropathy or drug resistance, significantly decrease the patients' quality of life and can even lead to interruption of treatment. Therefore, novel therapeutic drugs and strategies are urgently needed to improve MM therapy and patient outcomes. Here, we show that solamargine (SM), a steroidal alkaloid glycoside isolated from a Chinese herb Solanum nigrum L., exhibits promising anti-MM activity. In particular, SM suppressed the

Biomarkers in Multiple Sclerosis: An Up-to-Date Overview

During the last decades, the effort of establishing satisfactory biomarkers for multiple sclerosis has been proven to be very difficult, due to the clinical and pathophysiological complexities of the disease. Recent knowledge acquired in the domains of genomics-immunogenetics and neuroimmunology, as well as the evolution in neuroimaging, has provided a whole new list of biomarkers. This variety, though, leads inevitably to confusion in the effort of decision making concerning strategic and individualized therapeutics. In this paper, our primary goal is to provide the reader with a list of the

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

Циркуляция ДНК опухоли в Множественной миеломе: текущие понимания и перспективы на будущее.

Циркуляция ДНК опухоли (ctDNA) стала многообещающим минимально инвазивным биомаркером во множестве миеломы (ММ), обеспечивающим динамическое понимание бремени опухоли, клональной эволюции и молекулярной неоднородности. В отличие от традиционной диагностики на основе костного мозга, анализ CtDNA обеспечивает системный подход к оценке заболеваний и может лучше отражать пространственно неоднородные и внематочные заболевания. Последние достижения в области высокочувствительных молекулярных методов, включая цифровую цепную реакцию с капельной полимеразой и последовательность следующего поколения, п