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An integrated machine learning and mendelian randomization approach identifies SERPING1 as a prognostic biomarker associated with CD8 + T-cell infiltration in DLBCL.

BACKGROUND: SERPING1, which encodes the C1 inhibitor (C1-INH) of the complement system, and plays a key regulator in regulating inflammatory responses and immune homeostasis. SERPING1 is downregulated in various disease, this downregulation occurs through the body's negative feedback resulting from the overactivation of the complement system in diseases such as infections and acute inflammatory responses. Additionally, SERPING1 is vital for tumor immunomodulation. Diffuse large B-cell lymphoma (DLBCL) is a common and aggressive type of non-Hodgkin lymphoma. More treatment options are becoming

Non-invasive radiogenomic mapping of the SMARCAL1-driven ferroptotic niche is associated with longitudinal MRD-negative surveillance in early-stage NSCLC.

BACKGROUND: Post-operative molecular residual disease (MRD) detection using circulating tumor DNA (ctDNA) has been established as a sensitive biomarker for early recurrence risk stratification in early-stage non-small cell lung cancer (NSCLC). However, the biological heterogeneity of patients MRD-negative at baseline remains incompletely characterized, and a proportion subsequently experience MRD conversion and radiographic recurrence. We investigated whether pre-operative radiomic features could non-invasively capture the spatial organization of a ferroptosis-enriched, immune-active tumor mic

Dysfunction of Akt/FoxO3a/Atg7 regulatory loop magnifies obesity-regulated muscular mass decline.

BACKGROUND: Myoprotein degradation accelerates in obese individuals, resulting in a decline in muscular mass. Atg7 plays a crucial role in regulating protein stability and function through both autophagy-dependent and independent pathways. As obesity progresses, the expression of Atg7 gradually rises in muscle tissue. Nonetheless, the precise impact and mechanism of Atg7 in promoting muscle mass decline in obesity remain uncertain. The study aimed to elucidate the role and underly mechanism of Atg7 action in the context of obesity-induced muscle mass decline. METHODS: In this study, we establ

Berberine as a Multitarget Therapeutic Agent: Insights from Molecular Docking Studies.

Natural compounds are crucial in pharmacological research for modulating numerous biological processes. This is particularly helpful in the case of complex diseases and in overcoming challenges (e.g., drug resistance and adverse effects). Berberine, an isoquinoline alkaloid extracted from plants such as Berberis, Coptis, and Hydrastis species, exhibits a wide range of activities, including antidiabetic, anticancer, anti-inflammatory, antimicrobial, and antiviral. However, due to its low oral bioavailability (poor absorption, high first-pass metabolism, along with rapid elimination), further me

Macromolecular crowding: chemistry and physics meet biology (Ascona, Switzerland, 10-14 June 2012).

More than 60 years of biochemical and biophysical studies have accustomed us to think of proteins as highly purified entities that act in isolation, more or less freely diffusing until they find their cognate partner to bind to. While in vitro experiments that reproduce these conditions largely remain the only way to investigate the intrinsic properties of molecules, this approach ignores an important factor: in their natural milieu , proteins are surrounded by several other molecules of different chemical nature, and this crowded environment can considerably modify their behaviour. About 40%

Induction of interferon-λ contributes to TLR3 and RIG-I activation-mediated inhibition of herpes simplex virus type 2 replication in human cervical epithelial cells.

STUDY HYPOTHESIS: Is it possible to immunologically activate human cervical epithelial cells to produce antiviral factors that inhibit herpes simplex virus type 2 (HSV-2) replication? STUDY FINDING: Our results indicate that human cervical epithelial cells possess a functional TLR3/RIG-I signaling system, the activation of which can mount an Interferon-λ (IFN-λ)-mediated anti-HSV-2 response. WHAT IS KNOWN ALREADY: There is limited information about the role of cervical epithelial cells in genital innate immunity against HSV-2 infection. STUDY DESIGN, SAMPLES/MATERIALS, METHODS: We examined

Farnesylation-dependent kinetochore targeting of centromere protein F is essential for oocyte meiotic progression and female fertility.

BACKGROUND: During mammalian oocyte meiosis, accurate chromosome segregation critically depends on precise regulation of kinetochore-microtubule attachments, a process monitored by the spindle assembly checkpoint. While centromere protein F has been well characterized as a kinetochore-associated protein that stabilizes kinetochore-microtubule connections during mitosis, its functional mechanisms during meiosis remain poorly understood. In particular, there is still controversy over whether farnesylation modification governs localization and functionality of centromere protein F. Concurrently,

Next-generation precision medicine for mood disorders: reproducible blood biomarkers enable objective diagnostics, subtyping, and targeted therapeutics.

Mood disorders are highly prevalent in society, often disabling, and can lead to a reduced healthspan and lifespan, including by suicide. Depression and bipolar disorders are currently deemed to be chronic and/or treatment-refractory in up to half the patients treated. Additionally, depression and bipolar disorders need to be better distinguished, especially upon initial depressive presentations, as treatments can be quite different. Lack of widespread use of objective and/or quantitative information has hampered treatment and prevention efforts. We sought to uncover the underlying genomic and

Novel insights into the phylogenetic and metabolic diversity of preussia-like fungi.

The genus Preussia (Sporormiaceae, Pleosporales) represents one of the most diverse and metabolically active groups of ascomycetes. The genus is characterized by a complex taxonomic history involving the genera Sporormiella and Spororminula, which some authors consider synonyms of Preussia. However, the circumscription of these genera remains controversial, and the status of numerous species is unresolved. The present study aims to characterize strains of Preussia s.l. recovered during diversity surveys on marine and xerophytic substrates, explore their secondary metabolite profiles, and impro

Alterations in Abundance and Compartmentalization of miRNAs in Blood Plasma Extracellular Vesicles and Extracellular Condensates during HIV/SIV Infection and Its Modulation by Antiretroviral Therapy (ART) and Delta-9-Tetrahydrocannabinol (Δ9-THC).

In this follow-up study, we investigated the abundance and compartmentalization of blood plasma extracellular miRNA (exmiRNA) into lipid-based carriers-blood plasma extracellular vesicles (EVs) and non-lipid-based carriers-extracellular condensates (ECs) during SIV infection. We also assessed how combination antiretroviral therapy (cART), administered in conjunction with phytocannabinoid delta-9-tetrahydrocannabinol (THC), altered the abundance and compartmentalization of exmiRNAs in the EVs and ECs of SIV-infected rhesus macaques (RMs). Unlike cellular miRNAs, exmiRNAs in blood plasma may ser

m5C RNA methylation in cancer: from biological mechanism to clinical perspectives.

Cancer remains a significant global health threat, characterized by high morbidity and mortality rates. Despite advancements, numerous challenges persist in cancer treatment, underscoring the urgent need for novel therapeutic strategies. As a burgeoning area of cancer research, increasing evidence highlights the critical role of 5-methylcytosine (m5C) methylation in tumorigenesis, progression, and clinical application. In this review, we systematically review the biological mechanism and clinical translational potential of m5C RNA methylation in cancer and analyze in detail the dynamic interac

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… In cancers such as colorectal cancer (CRC) [ 27 ], lung squamous cell carcinoma [ 79 ], and ovarian cancer [ 80 ], YBX1 enhances RNA stability or promotes translation, thereby contributing to cancer progression. … It also influences tumor cell proliferation, invasion, metastasis potential, and autophagy by dynamically regulating RNA stability and protein translation efficiency [ 83 , 84 ]. …

Revealing G4 Structures as Drug Targets: Exploring the Potential of Novel Therapeutic Agents.

G-quadruplex (G4) structures represent noncanonical secondary formations found in DNA and RNA. Recent research reveals that G4s are abnormally enriched in various cancers, with closely linked to malignancy, metastatic potential, and prognosis. These structures have emerged as promising biomarkers for cancer with notable clinical relevance. Concurrently, investigations into compounds that selectively recognize DNA or RNA G4s as potential anticancer agents offer new avenues for early cancer diagnosis and therapeutic strategies. This review systematically analyzes the chemical structural characte

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… Research has demonstrated that rG4s, with their unique thermodynamic stability and conformational plasticity, establish a multidimensional regulatory network that links RNA stability control, precise translational guidance, and functional organization within the nucleus. … The presence of rG4 structures affects RNA stability Characterized by minimal structural dynamics, rG4s adopt thermodynamically stable conformations, typically manifesting as compact, closed architectures. …

Reciprocal regulation between m6 A modifications and non-coding RNAs: emerging roles in cancer therapeutic resistance.

In recent years, the interplay between N6-methyladenosine (m6A) modifications and non-coding RNAs (ncRNAs) has emerged as a pivotal research area, owing to their crucial involvement in the pathophysiological mechanisms underlying various diseases. A significant hurdle in cancer therapy is therapeutic resistance, which frequently contributes to adverse patient outcomes. Recent investigations have underscored the vital role that interactions between m6A modifications and ncRNAs play in mediating cancer therapeutic resistance via the MAPK, PI3K/Akt/mTOR, Wnt/β-catenin, HIPPO, and NF-κB pathways.

Decoding the epitranscriptome: a new frontier for cancer therapy and drug resistance.

As the role of RNA modification in gene expression regulation and human diseases, the "epitranscriptome" has been shown to be an important player in regulating many physiological and pathological processes. Meanwhile, the phenomenon of cancer drug resistance is becoming more and more frequent, especially in the case of cancer chemotherapy resistance. In recent years, research on relationship between post-transcriptional modification and cancer including drug resistance has become a hot topic, especially the methylation of the sixth nitrogen site of RNA adenosine-m6A (N6-methyladenosine). m6A m

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… At the same time, study by Zhang et al. revealed that m 6 A modification of tRNA methyltransferase activator subunit 11 (TRIM11) by METTL3 could enhance TRIM11 RNA stability and led to inhibited apoptosis in vitro and promoted cisplatin (DDP: platinum-based chemotherapeutic drug) resistance in vivo in … Moreover, TET2 has also been shown to regulate RNA stability via m 5 C modification in RNA [ 225 ]. The involvement of TETs in cancer has been reported. …

The use of RNA-based treatments in the field of cancer immunotherapy.

Over the past several decades, mRNA vaccines have evolved from a theoretical concept to a clinical reality. These vaccines offer several advantages over traditional vaccine techniques, including their high potency, rapid development, low-cost manufacturing, and safe administration. However, until recently, concerns over the instability and inefficient distribution of mRNA in vivo have limited their utility. Fortunately, recent technological advancements have mostly resolved these concerns, resulting in the development of numerous mRNA vaccination platforms for infectious diseases and various t

RNA N 6-Methyladenosine in Cancer Metastasis: Roles, Mechanisms, and Applications.

Cancer metastasis is a symptom of adverse prognosis, a prime origin of therapy failure, and a lethal challenge for cancer patients. N 6-methyladenosine (m6A), the most prevailing modification in messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs) of higher eukaryotes, has attracted increasing attention. Growing studies have verified the pivotal roles of m6A methylation in controlling mRNAs and ncRNAs in diverse physiological processes. Remarkably, recent findings have showed that aberrant methylation of m6A-related RNAs could influence cancer metastasis. In this review, we illuminate how m6A m

Spiegelmer Aptamers: Innovative Approach in Breast Cancer.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, emphasizing the urgent need for improved diagnostic and therapeutic strategies. Aptamers which are synthetic oligonucleotides that specifically bind to target molecules, offer high affinity, low immunogenicity, and superior tumor penetration compared to antibodies. However, their clinical translation has been limited by instability in biological systems. Spiegelmers, a novel class of mirror-image aptamers composed of L-nucleotides, overcome this limitation through intrinsic nuclease resistance an

Current concepts of the crosstalk between lncRNA and E2F1: shedding light on the cancer therapy.

Long noncoding RNAs (lncRNAs) constitute a distinctive subset of RNA molecules with limited protein-coding potential, which exert crucial impacts on various biological activities. In the context of cancer, dysregulated lncRNAs function as essential regulators that affect tumor initiation and malignant progression. These lncRNAs serve as competitive endogenous RNAs (ceRNAs) through sponging microRNAs and regulating the expression of targeted genes. Moreover, they also directly bind to RNA-binding proteins, which can be integrated into a complex mechanistic network. E2F1, an extensively studied

Exploring the impact of m6A modification on immune diseases: mechanisms and therapeutic implication.

N6-methyladenosine (m6A) is a chemical modification of RNA and has become a widely discussed topic among scientific researchers in recent years. It is distributed in various organisms, including eukaryotes and bacteria. It has been found that m6A is composed of writers, erasers and readers and is involved in biological functions such as splicing, transport and translation of RNA. The balance of the human immune microenvironment is important for human health abnormalities. Increasing studies have found that m6A affects the development of immune diseases such as inflammatory enteritis and system

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… Among them, m 6 A is involved in multiple aspects of mRNA, including splicing, nuclear export, translation, and RNA stability ( 14 , 31 , 32 ) ( Figure 2 ). … N6-methyladenosine-dependent regulation of messenger Rna stability. Nature. (2014) 505:117–20. doi: 10.1038/nature12730 26. Zaccara S, Jaffrey SR. A unified model for the function of Ythdf proteins in regulating M(6)a-modified Mrna. …

Структурно-ориентированное понимание специфичности 2ДГ-III реберосчег.

Рибосчемы сохраняют некодированные домена РНК, в основном расположенные на 5'-конец бактериальных MRNA, которые служат регулятором генного экспрессии. Недавно третий класс 2Дексигуанозин реберосколка.2'-dG-III) был идентифицирован из семейства рибоколдов, проявляющих сопоставимую связь с 2ДиДжи, Гунанин и гуанозин. Чтобы прояснить уникальный механизм распознавания лиганда, мы раскрыли его кристаллы в комплексе с различными производными пурины, включая 2ДиДжи, Гунанин и гуанозин. Трехсторонняя структура показывает типичную архитектуру, похожую на вилку, с three вырезки, соединяющиеся в центре t