Melanoma is a highly aggressive tumor derived from melanocytes. In recent years, the incidence and mortality of melanoma have gradually increased, seriously threatening human health. Classic ...treatments like surgery, chemotherapy, and radiotherapy show very limited efficacy. Due to the high immunogenicity of melanoma cells, immune checkpoint inhibitors have received considerable attention as melanoma treatments. One such therapy is blockade of programmed cell death‐1 (PD‐1), which is one of the most important negative immune regulators and is mainly expressed on activated T cells. Disruption of the interactions between PD‐1 and its ligands, programmed death‐ligand 1 (PD‐L1) or programmed death‐ligand 2 (PD‐L2) rejuvenates exhausted T cells and enhances antitumor immunity. Although PD‐1 blockade therapy is widely used in melanoma, a substantial proportion of patients still show no response or short durations of remission. Recent researches have focused on revealing the underlying mechanisms for resistance to this treatment and improving its efficacy through combination therapy. Here, we will introduce the resistance mechanisms associated with PD‐1 blockade therapy in melanoma and review the combination therapies available.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS ...has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of
; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of
, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Introduction
Pancreatic cancer is one of the most fatal malignancies and primary prevention strategies are limited. Epidemiological studies focusing on the association between folate intake and ...pancreatic cancer risk have reported inconsistent findings.
Methods
A systematic search of the literature was conducted using the PubMed and EMBASE databases. A systematic review and meta-analysis of eligible studies was performed to assess the association between folate intake and risk of pancreatic cancer.
Results
A total of 16 studies involving 5654 cases and 1,009,374 individuals were included. The result showed a significant association of folate intake with a decreased risk of pancreatic cancer, with a pooled OR of 0.82 (95% CI: 0.69–0.97,
P
= 0.019) for the highest category of intake vs. the lowest. The data suggested that high intake of folate may contribute to the prevention of pancreatic cancer. However, the association was observed only in case–control studies (OR = 0.78, 95% CI: 0.65–0.93,
P
= 0.006), but not in cohort studies (RR = 0.85, 95% CI: 0.66–1.09,
P
= 0.244). Dose–response meta-analysis showed that an increment of folate intake (100 μg/day) was marginally associated with the risk of pancreatic cancer, with a pooled OR of 0.97 (95% CI: 0.93–1.00,
P
= 0.053).
Conclusion
High folate intake might be inversely associated with pancreatic cancer risk, which needs to be confirmed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Dysbiosis of gut microbiota and metabolic pathway disorders are closely related to the ulcerative colitis. Through network pharmacology, we found that puerarin is a potential ingredient that can ...improve the crypt deformation and inflammatory infiltration in mice, and decrease the levels of IL-1β, IL-6 and TNF-α significantly.
Listeria
,
Alistipes
and
P. copri
gradually became dominant bacteria in UC mice, which were positively correlated with inflammatory factors. Puerarin effectively improved dysbiosis by reducing the abundance of
Alistipes
,
P. copri
and
Veillonella
, and increasing the level of
Desulfovibrionacea
. Correlation network and metabolic function prediction analysis of the microbiota showed that they formed a tightly connected network and were widely involved in carbohydrate metabolism and amino acid metabolism. Specifically, we observed significant changes in the tryptophan metabolism pathway in DSS mice, with an increase in the abundance of
Bacteroidetes
and
Enterobacteriaceae
involved in tryptophan metabolism. However, this metabolic disorder was alleviated after puerarin treatment, including the reversal of 3-HAA levels and an increase in the abundance of
Rhodobacteraceae
and
Halomonadaceae
involved in kynurenine metabolism, as well as a significant increase in the purine metabolite guanosine. In conclusion, our study suggests that puerarin has a good therapeutic effect on UC, which is partially achieved by restoring the composition and abundance of gut microbiota and their metabolism.
Chronic lymphocytic leukemia (CLL), a common type of B cell chronic lymphoproliferative disorder in adults, has witnessed enormous development in its treatment in recent years. New drugs such as ...ibrutinib, idelalisib, and venetoclax have achieved great success in treating relapsed and refractory (R/R) CLL. In addition, with the development of immunotherapy, chimeric antigen receptor-engineered T cells (CAR-T) therapy, a novel adoptive immune treatment, has also become more and more important in treating R/R CLL. It combines the advantages of T cells and B cells via ex vivo gene transfer technology and is able to bind targets recognized by specific antibodies without antigen presentation, thus breaking the restriction of major histocompatibility complex. So far, there have been lots of studies exploring the application of CAR-T therapy in CLL. In this review, we describe the structure of chimeric antigen receptor, the preclinical, and clinical results of CAR-T therapy against CLL, along with its adverse events and advances in efficacy.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Since digital technology has had a significant impact on the fashion industry, digital fashion has become a hot topic in today's society. Currently, research on digital fashion is focused on the ...transformation of enterprise marketing strategies and the discussion of digital technology. Despite this, the current study does not include an analysis of the audience's emotional and cognitive responses to digital fashion on social networking platforms. A comprehensive analysis and discussion of 52,891 posts about digital fashion and virtual fashion published on social networking sites was conducted using k-means clustering analysis, Latent Dirichlet Allocation (LDA) topic modeling, and sentiment analysis in this study. The study examines the public's perception and hot topics about digital fashion, as well as the industry's development situation and trends. According to the findings, both positive and neutral emotions accompany the public's attitude toward digital fashion. There is a wide range of topics covered in the discussion. Innovations in digital technology have impacted the creation of jobs, talent demand, marketing strategies, profit forms, and industrial chain innovation of fashion-related businesses. Researchers in related fields will find this study useful not only as a reference for research methods and directions, but also as a source of references for research methodology. A case study and data reference will also be provided to industry practitioners.
Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the ...causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels.
We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses.
The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features.
The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
NOTCH1 mutation is an essential molecular biologic aberration in chronic lymphocytic leukemia (CLL). CLL patients with NOTCH1 mutation have shown an unfavorable survival and a poor response to ...chemoimmunotherapy. This study aims to present the mechanisms of adverse prognosis caused by NOTCH1 mutation from the perspective of the splicing factor heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1).
The microarray data in Gene Expression Omnibus datasets were analyzed by bioinformatics and the function of hnRNPA1 was checked by testing the proliferation and apoptosis of CLL-like cell lines. Afterward, quantitative reverse transcription-polymerase chain reaction and Western blotting were applied to explore the relationship among NOTCH1, c-Myc, and hnRNPA1.
RNA splicing was found to play a vital part in NOTCH1-mutated CLL cells; hence, hnRNPA1 was selected as the focus of this study. Higher expression of hnRNPA1 validated in primary NOTCH1-mutated CLL samples could promote proliferation and inhibit apoptosis in CLL. The expression of hnRNPA1 increased when NOTCH1 signaling was activated by transfection with NOTCH1 intracellular domain (NICD)-overexpressed adenovirus vector and declined after NOTCH1 signaling was inhibited by NOTCH1-shRNA. Higher expression of c-Myc was observed in NICD-overexpressed cells and hnRNPA1 expression was downregulated after applying c-Myc inhibitor 10058-F4. Moreover, in NICD-overexpressed cells, hnRNPA1 expression decreased through c-Myc inhibition.
Overexpression of c-Myc-dependent hnRNPA1 could promote proliferation and inhibit apoptosis in NOTCH1-mutated CLL cells, which might partly account for the poor prognosis of patients with NOTCH1 mutation.
As the largest immune organ of the human body, the intestine also plays a vital role in nutrient digestion and absorption. Some vegetables are considered to have improvement effects on the intestine. ...This experiment explored the effects of freeze-dried asparagus, broccoli and cabbage powder on the intestinal immune homeostasis and microflora of mice. Thirty-two mice were divided into four groups (
= 8), including control group (fed normal diet), asparagus group (fed normal diet with 5% asparagus power), broccoli group (fed normal diet with 5% broccoli power) and cabbage group (fed normal diet with 5% cabbage power). The experiment lasted 21 days. The results showed that the serum immunoglobulin concentration (IgA and IgM) and intestinal cytokine content (like IFN-γ and TNF-α) were increased after vegetable powder supplement. The experiment also detected that vegetable powder supplementation changed intestinal flora and their metabolites (short-chain fatty acid), which showed that the abundance of
and
were decreased, while the abundance of
and
as well as propionic acid and butyric acid contents were increased. Together, these vegetable powders, especially cabbage, changed the intestinal immune response and microbial activity of mice.
Psychiatric disorder, including bipolar disorder (BD), major depression (MDD), and schizophrenia (SCZ), affects millions of persons around the world. Understanding the disease causal mechanism ...underlying the three diseases and identifying the modifiable risk factors for them hold the key for the development of effective preventative and treatment strategies. We used a two-sample Mendelian randomization method to assess the causal effect of insomnia on the risk of BD, MDD, and SCZ in a European population. We collected one dataset of insomnia, three of BD, one of MDD, and three of SCZ and performed a meta-analysis for each trait, further verifying the analysis through extensive complementarity and sensitivity analysis. Among the three psychiatric disorders, we found that only insomnia is causally associated with MDD and that higher insomnia increases the risk of MDD. Specifically, the odds ratio of MDD increase of insomnia is estimated to be 1.408 95% confidence interval (CI): 1.210–1.640,
p
= 1.03E-05 in the European population. The identified causal relationship between insomnia and MDD is robust with respect to the choice of statistical methods and is validated through extensive sensitivity analyses that guard against various model assumption violations. Our results provide new evidence to support the causal effect of insomnia on MDD and pave ways for reducing the psychiatric disorder burden.
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