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Open Access
January 24, 2023
Abstract
Immune checkpoint inhibitors (ICIs) like programmed cell death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitor have shown considerable efficacy in several important cancers including primary liver cancer (PLC) like hepatocellular carcinoma and cholangiocarcinoma. However, only some patients with PLC will benefit, so combination therapy and biomarker classification detected by next-generation sequencing or immunohistochemistry are very important. Herein, we briefly summarize ICI-based therapies and stratify these evolving therapies for advanced PLC into three stages of immunotherapies Mark (Mk.) 1.0, 2.0, and 3.0. We illustrated the significance of ICI monotherapy (Mk. 1.0), offering combinational approaches with traditional strategies (Mk. 2.0) and additional locoregional therapy (Mk. 3.0) to achieve longer survival and even meet the “No Evidence of Disease” status. We also highlight the importance of biomarkers and prognostic factors for patients with advanced PLC treated with ICI-based therapies. Multidisciplinary team management should be investigated and collaborated closely to manage adverse events and sequential therapy suggestions for patients.
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Open Access
January 16, 2023
Abstract
Antibodies, as one of the most important components of host adaptive immune system, play an important role in defense of infectious disease, immune surveillance, and autoimmune disease. Due to the development of recombinant antibody technology, antibody therapeutics become the largest and rapidly expanding drug to provide major health benefits to patients, especially for the treatment of cancer patients. Many antibody-based therapeutic strategies have been developed including monoclonal antibodies, antibody-drug conjugates, bispecific and trispecific antibodies and pro-antibodies with promising results from both clinical and pre-clinical trials. However, the response rate and side-effect still vary between patients with undefined mechanisms. Here, we summarized the current and future perspectives of antibody-based cancer immunotherapeutic strategies for designing next-generation drugs.
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Open Access
January 16, 2023
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Open Access
January 13, 2023
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Open Access
January 6, 2023
Abstract
Non-alcoholic steatohepatitis (NASH) with metabolic syndrome is increasing to be a main cause of hepatocellular carcinoma (HCC). However, the mechanism of tumorigenesis in NASH induced HCC is still not clear. In this perspective, we will discuss the recent progress that has been made to understand the genetic change and the immune microenvironment of HCC, and the remaining questions. Based on the current study, NASH-HCC is likely to have novel mechanism, which needs more investigation in future.
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Open Access
December 19, 2022
Abstract
Recurrent pregnancy loss (RPL) has become an important reproductive health issue worldwide. RPL affects about 2%–3% of reproductive-aged women, and makes serious threats to women’s physical and mental health. However, the etiology of approximately 50% of RPL cases remains unknown (unexplained RPL), which poses a big challenge for clinical management of these patients. RPL has been widely regarded as a complex disease where its etiology has been attributed to numerous factors. Heretofore, various risk factors for RPL have been identified, such as maternal ages, genetic factors, anatomical structural abnormalities, endocrine dysfunction, prethrombotic state, immunological factors, and infection. More importantly, development and applications of next generation sequencing technology have significantly expanded opportunities to discover chromosomal aberrations and single gene variants responsible for RPL, which provides new insight into its pathogenic mechanisms. Furthermore, based upon patients’ diagnostic evaluation and etiologic diagnosis, specific therapeutic recommendations have been established. This review will highlight current understanding and recent advances on RPL, with a special focus on the immunological and genetic etiologies, clinical diagnosis and therapeutic management.
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Open Access
November 30, 2022
Abstract
Xenobiotic receptors are traditionally defined as xenobiotic chemical-sensing receptors, the activation of which transcriptionally regulates the expression of enzymes and transporters involved in the metabolism and disposition of xenobiotics. Emerging evidence suggests that “xenobiotic receptors” also have diverse endobiotic functions, including their effects on lipid metabolism and energy metabolism. Dyslipidemia is a major risk factor for cardiovascular disease, diabetes, obesity, metabolic syndrome, stroke, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Understanding the molecular mechanism by which transcriptional factors, including the xenobiotic receptors, regulate lipid homeostasis will help to develop preventive and therapeutic approaches. This review describes recent advances in our understanding the atypical roles of three xenobiotic receptors: aryl hydrocarbon receptor (AhR), pregnane X receptor (PXR), and constitutive androstane receptor (CAR), in metabolic disorders, with a particular focus on their effects on lipid and glucose metabolism. Collectively, the literatures suggest the potential values of AhR, PXR and CAR as therapeutic targets for the treatment of NAFLD, NASH, obesity and diabetes, and cardiovascular diseases.
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Open Access
November 22, 2022
Abstract
Ovarian reserve is essential for fertility and influences healthy aging in women. Advanced maternal age correlates with the progressive loss of both the quantity and quality of oocytes. The molecular mechanisms and various contributing factors underlying ovarian aging have been uncovered. In this review, we highlight some of critical factors that impact oocyte quantity and quality during aging. Germ cell and follicle reserve at birth determines reproductive lifespan and timing the menopause in female mammals. Accelerated diminishing ovarian reserve leads to premature ovarian aging or insufficiency. Poor oocyte quality with increasing age could result from chromosomal cohesion deterioration and misaligned chromosomes, telomere shortening, DNA damage and associated genetic mutations, oxidative stress, mitochondrial dysfunction and epigenetic alteration. We also discuss the intervention strategies to delay ovarian aging. Both the efficacy of senotherapies by antioxidants against reproductive aging and mitochondrial therapy are discussed. Functional oocytes and ovarioids could be rejuvenated from pluripotent stem cells or somatic cells. We propose directions for future interventions. As couples increasingly begin delaying parenthood in life worldwide, understanding the molecular mechanisms during female reproductive aging and potential intervention strategies could benefit women in making earlier choices about their reproductive health.
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Open Access
October 19, 2022
Abstract
Microbubbles have been the earliest and most widely used ultrasound contrast agents by virtue of their unique features: such as non-toxicity, intravenous injectability, ability to cross the pulmonary capillary bed, and significant enhancement of echo signals for the duration of the examination, resulting in essential preclinical and clinical applications. The use of microbubbles functionalized with targeting ligands to bind to specific targets in the bloodstream has further enabled ultrasound molecular imaging. Nevertheless, it is very challenging to utilize targeted microbubbles for molecular imaging of extravascular targets due to their size. A series of acoustic nanomaterials have been developed for breaking free from this constraint. Especially, biogenic gas vesicles, gas-filled protein nanostructures from microorganisms, were engineered as the first biomolecular ultrasound contrast agents, opening the door for more direct visualization of cellular and molecular function by ultrasound imaging. The ordered protein shell structure and unique gas filling mechanism of biogenic gas vesicles endow them with excellent stability and attractive acoustic responses. What’s more, their genetic encodability enables them to act as acoustic reporter genes. This article reviews the upgrading progresses of ultrasound contrast agents from microbubbles to biogenic gas vesicles, and the opportunities and challenges for the commercial and clinical translation of the nascent field of biomolecular ultrasound.
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Open Access
September 5, 2022
Abstract
The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic consequences. Time-restricted feeding (TRF), with all calories consumed within less than 12-h per day, can improve metabolism and extend lifespan. A major component of TRF in humans is caloric restriction, which contributes significantly to the beneficial effects of TRF in humans. By comparison, TRF effects in rodents can be independent of caloric restriction and show day/night phase specificity. TRF could alleviate metabolic abnormalities due to circadian disruption, but its effects appear independent of the circadian clock in rodents. Understanding neuroendocrine mechanisms underlying clock-mediated metabolic regulation will shed light on the metabolic effects of temporal meal patterns.
