Abstract
Immune checkpoint inhibitors (ICIs) are promising agents for treating melanoma. Given that autoimmune skin diseases exhibit hyper immune reaction, investigation of immune cells from ...autoimmune skin disease is crucial to validate the effectiveness of ICIs in melanoma treatment. We employed multipanel markers to predict the response to immune checkpoint inhibitors by characterizing the gene expression signatures of skin immune cells in systemic lupus erythematosus (SLE), atopic dermatitis (AD), and psoriasis (PS). By analyzing single-cell RNA sequencing data from each dataset, T cell gene signatures from autoimmune skin diseases exhibit a complex immune response in tumors that responded to immunotherapy. Based on that CD86 and CD80 provide essential costimulatory signals for T cell activation, we observed that interaction of CD86 signaling has been enhanced in the T cells of patients with SLE, AD, and PS. Our analysis revealed a common increase in CD86 signals from dendritic cells (DCs) to T cells in patients with SLE, AD, and PS, confirming that dendritic cells produce pro-inflammatory cytokines to activate T cells. Thus, we hypothesize that T cell gene signatures from autoimmune skin diseases exhibit a pro-inflammatory response and have the potential to predict cancer immunotherapy. Our study demonstrated that T cell gene signatures derived from inflammatory skin diseases, particularly SLE and PS, hold promise as potential biomarkers for predicting the response to immune checkpoint blockade therapy in patients with melanoma. Our data provide an understanding of the immune-related characteristics and differential gene expression patterns in autoimmune skin diseases, which may represent promising targets for melanoma immunotherapy.
Ginseng is usually consumed as a daily food supplement to improve health and has been shown to benefit skeletal muscle, improve glucose metabolism, and ameliorate muscle-wasting conditions, ...cardiovascular diseases, stroke, and the effects of aging and cancers. Ginseng has also been reported to help maintain bone strength and liver (digestion, metabolism, detoxification, and protein synthesis) and kidney functions. In addition, ginseng is often used to treat age-associated neurodegenerative disorders, and ginseng and ginseng-derived natural products are popular natural remedies for diseases such as diabetes, obesity, oxidative stress, and inflammation, as well as fungal, bacterial, and viral infections. Ginseng is a well-known herbal medication, known to alleviate the actions of several cytokines. The article concludes with future directions and significant application of ginseng compounds for researchers in understanding the promising role of ginseng in the treatment of several diseases. Overall, this study was undertaken to highlight the broad-spectrum therapeutic applications of ginseng compounds for health management.
Anti-corrosion metal protection of the 2D structured graphene oxide (GO) was investigated in this study using its intrinsic impermeability against reactive molecules stemming from the small geometric ...pore size and π-orbital repelling fields of graphene. The electrophoretic deposition (EPD) of GO sheets on metals is an attractive coating method but the negatively-charged GO only allows the anodic EPD process, which makes it difficult to achieve high-quality coating layers due to gas bubbling and electrochemical oxidation of metals. Thus, we imposed the positive charge to GO sheets using p-phenylenediamine (PPD) and successfully carried out the cathodic EPD in the ethanol aqueous solution. The cathodic EPD of GO on cupper provided a linear growth rate with both deposition time and voltage providing the thickness over 6.0 μm in a void-free and robust feature, which could hardly be achieved by other coating methods. Converting the GO coating to the reduced GO (RGO) by thermal reduction, we successfully increased the RGO adhesion strength up to the highest adhesion grade of 5B in the cross-cut adhesion test. An excellent anti-corrosion protection capability of the developed RGO coating was demonstrated by a decreased corrosion current density and increased corrosion potential in potentiodynamic polarization analysis.
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Myostatin (MSTN) is a well-reported negative regulator of muscle growth and a member of the transforming growth factor (TGF) family. MSTN has important functions in skeletal muscle (SM), and its ...crucial involvement in several disorders has made it an important therapeutic target. Several strategies based on the use of natural compounds to inhibitory peptides are being used to inhibit the activity of MSTN. This review delivers an overview of the current state of knowledge about SM and myogenesis with particular emphasis on the structural characteristics and regulatory functions of MSTN during myogenesis and its involvements in various muscle related disorders. In addition, we review the diverse approaches used to inhibit the activity of MSTN, especially
in silico
approaches to the screening of natural compounds and the design of novel short peptides derived from proteins that typically interact with MSTN.
Type 2 diabetes mellitus (T2DM) is a growing global public health issue, and dipeptidyl peptidase-4 (DPP-4) is a potential therapeutic target in T2DM. Several synthetic anti-DPP-4 medications can be ...used to treat T2DM. However, because of adverse effects, there is an unmet demand for the development of safe and effective medications. Natural medicines are receiving greater interest due to the inherent safety of natural compounds.
Glycyrrhiza uralensis
(licorice) is widely consumed and used as medicine. In this study, we investigated the abilities of a crude water extract (CWE) of
G. uralensis
and two of its constituents (licochalcone A (LicA) and licochalcone B (LicB)) to inhibit the enzymatic activity of DPP-4
in silico
and
in vitro
.
In silico
studies showed that LicA and LicB bind tightly to the catalytic site of DPP-4 and have 11 amino acid residue interactions in common with the control inhibitor sitagliptin. Protein-protein interactions studies of LicA-DPP4 and LicB-DPP4 complexes with GLP1 and GIP reduced the DPP-4 to GLP1 and GIP interactions, indicated that these constituents might reduce the degradations of GLP1 and GIP. In addition, molecular dynamics simulations revealed that LicA and LicB stably bound to DPP-4 enzyme. Furthermore, DPP-4 enzyme assay showed the CWE of
G. uralensis
, LicA, and LicB concentration-dependently inhibited DPP-4; LicA and LicB had an estimated IC
50
values of 347.93 and 797.84 μM, respectively. LicA and LicB inhibited DPP-4 at high concentrations, suggesting that these compounds could be used as functional food ingredients to manage T2DM.
Immunoglobulin-like cell adhesion molecule (IgLON4) is a glycosylphosphatidylinositol-anchored membrane protein that has been associated with neuronal growth and connectivity, and its deficiency has ...been linked to increased fat mass and low muscle mass. Adequate information on IgLON4 is lacking, especially in the context of skeletal muscle. In this study, we report that IgLON4 is profusely expressed in mouse muscles and is intensely localized on the cell membrane. IgLON4 expression was elevated in CTX-injected mouse muscles, which confirmed its role during muscle regeneration, and was abundantly expressed at high concentrations at cell-to-cell adhesion and interaction sites during muscle differentiation. IgLON4 inhibition profoundly affected myotube alignment, and directional analysis confirmed this effect. Additionally, results demonstrating a link between IgLON4 and lipid rafts during myogenic differentiation suggest that IgLON4 promotes differentiation by increasing lipid raft accumulation. These findings support the notion that a well-aligned environment promotes myoblast differentiation. Collectively, IgLON4 plays a novel role in myogenesis and regeneration, facilitates myotube orientation, and is involved in lipid raft accumulation.
Abstract Serine is a key contributor to the generation of one-carbon units for DNA synthesis during cellular proliferation. In addition, it plays a crucial role in the production of antioxidants that ...prevent abnormal proliferation and stress in cancer cells. In recent studies, the relationship between cancer metabolism and the serine biosynthesis pathway has been highlighted. In this context, 3-phosphoglycerate dehydrogenase (PHGDH) is notable as a key enzyme that functions as the primary rate-limiting enzyme in the serine biosynthesis pathway, facilitating the conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate. Elevated PHGDH activity in diverse cancer cells is mediated through genetic amplification, posttranslational modification, increased transcription, and allosteric regulation. Ultimately, these characteristics allow PHGDH to not only influence the growth and progression of cancer but also play an important role in metastasis and drug resistance. Consequently, PHGDH has emerged as a crucial focal point in cancer research. In this review, the structural aspects of PHGDH and its involvement in one-carbon metabolism are investigated, and PHGDH is proposed as a potential therapeutic target in diverse cancers. By elucidating how PHGDH expression promotes cancer growth, the goal of this review is to provide insight into innovative treatment strategies. This paper aims to reveal how PHGDH inhibitors can overcome resistance mechanisms, contributing to the development of effective cancer treatments.
Large language models have exhibited remarkable proficiency in various domains and tasks including Numerical Reasoning task. However, datasets for Numerical Reasoning tasks targeted by LLMs often ...contain relatively few number of numerical values within the context. This raises doubts about whether LLMs can infer well and provide accurate answers even when presented with contexts including many numerical values. Indeed in a simple pilot study, we have found that LLM's ability to distinguish between essential and non-essential numerical values when solving numerical reasoning tasks is quite poor. To relieve this phenomenon, this paper proposes a framework to improve the robustness of LLMs in handling irrelevant numerical values for problem-solving by augmenting the original context of the problem while adding extra numerical values to the context. The experiment demonstrated that the model trained on the augmented dataset by our methodology increased robustness in Numerical Reasoning tasks with higher accuracies.
Granulocyte-monocyte progenitors (GMPs) have been previously defined for their potential to generate various myeloid progenies such as neutrophils and monocytes. Although studies have proposed ...lineage heterogeneity within GMPs, it is unclear if committed progenitors already exist among these progenitors and how they may behave differently during inflammation. By combining single-cell transcriptomic and proteomic analyses, we identified the early committed progenitor within the GMPs responsible for the strict production of neutrophils, which we designate as proNeu1. Our dissection of the GMP hierarchy led us to further identify a previously unknown intermediate proNeu2 population. Similar populations could be detected in human samples. proNeu1s, but not proNeu2s, selectively expanded during the early phase of sepsis at the expense of monocytes. Collectively, our findings help shape the neutrophil maturation trajectory roadmap and challenge the current definition of GMPs.
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•GMPs are heterogeneous at the transcriptomic and proteomic level•An early committed neutrophil progenitor (proNeu1) exists within GMPs•proNeu1 gives rise to proNeu2, sequentially differentiating into mature neutrophil•proNeu1 specifically expands during emergency granulopoiesis
The daily production of circulating neutrophils depends on committed and proliferative progenitors, but the ontogenic pathway of neutrophil progenitors remains poorly defined. Integrating multiple single-cell-based technologies, Kwok et al. resolve GMP heterogeneity to identify an early committed neutrophil progenitor (proNeu1) and map out the entire neutrophil developmental pathway in steady state and emergency granulopoiesis.
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