In Part I,1 we congratulated five outstanding researchers winning the 2021 Outstanding Research Paper Awards who were selected from all research articles published in 2021 issues of the Journal of the Chinese Medical Association (JCMA) which got a new achievement of 2021 impact factor (IF) as 3.396 at the Annual Meeting of the Chinese Medical Association-Taipei (CMA-Taipei) on July 16, 2022, Taipei, Taiwan.1,2 The current editorial is a “Part II,” which introduces another four excellent researchers with their academic professions to explore a brand-new vision for future patient’s care.3–6 By the way, the top-cited article is simultaneously announced here.7
Dr. Huang and colleagues tried their best to explore the possible underlying pathophysiology about bronchopulmonary dysplasia (BPD) in newborns, and their findings made them win one of the CMA-Taipei Outstanding Research Work Awards.3 BPD, the main cause of infant’s death and if survived, a severe long-term complication, secondary to respiratory distress syndrome and acute lung injury-related respiratory failure, which may deteriorate the overall quality of life of newborns and their subsequent life (asthma, repeated respiratory infection, low exercise capacity and early-onset emphysema, and subsequent development of pulmonary-cardiovascular dysfunction), is frequently occurred in premature deliveries (<37 weeks of gestational age).8–10 Oxygen (O2) supplement is always needed for these premature newborns due to their dysfunction of the respiratory system, which cannot maintain adequate oxygen to supply to the body, resulting in an uncompensated hypoxia. However, an overdose of O2 supply may result in hyperoxia of lung, causing lung injury and subsequently implicated in the pathogenesis of BPD. Many altered depositions of various cytokines, proinflammatory factors, and inflammatory factors are detected during the lung injury, which include upregulation of chemokine-mediated signaling and immune cell chemotaxis, and defective development of T lymphocytes.10 All are reported to be associated with the development of BPD.10 As mentioned by Dr. Huang, the role of tripartite motif protein 72 (TRIM72) in the pathogenesis of hyperoxia-induced lung injury is uncertain.3 Therefore, they conducted both in vivo animal study using Sprague-Dawley rat model and in vitro experiments using both epithelial pulmonary cell lines of rat alveolar type II epithelial cell line and human epithelial lung cancer cell line to test what happened during hyperoxia status.3 They found hyperoxia resulted in overexpression of TRIM72, leading to alveolar epithelial cell death and modifying extracellular matrix remodeling, and then they proposed that upregulation of TRIM72 is a possible cause contributing to hyperoxia-induced lung injury and the development of BPD.3 Although their study was relatively solid and proposal was believable, their data seemed to conflict with those of the previous study to favor the protective TRIM72 in alveolar epithelial cell type I and type II, because they found that injury-related TRIM72 upregulation is transient, and tapering of the TRIM72 level correlates with the rising of hydroxyproline level in the lung, and additionally, ablation of TRIM72 reduces overall alveolar epithelial integrity, histological destruction, and barrier function of lung.11 Similar to the concept of the healing process,7 destroying and repairing processes occur continuously, parallelly, and in overlap mediated through complex cross talk, resembling the concurrent upregulation of proinflammatory and immune-modulatory immune system at the injured tissues, supposing that lung tissues may share similar compensatory cellular protective mechanisms against different injurious insults, and postinsult responses are tightly orchestrated in a strictly controlled fashion.11 Therefore, the longitudinal and/or dynamic study is of need to clarify the real role of TRIM72 in the pathogenesis of lung fibrosis and the development of BPD.
Besides a large economic and social burdens by metabolic and cardiovascular system-related morbidity and mortality,12 cancer is another leading cause to shorten the lifespan of humans. Conventionally, surgery, radiotherapy, chemotherapy, and a combination of any are the main weapons used to be against cancer.13 However, the therapeutic efficacy is still suboptimal, and many patients will be situated with persistent disease status or recur their diseases, and finally die of cancer. All make the urgent need to search for agents or drugs fulfilling the criteria with more effectiveness and fewer side effects for the treatment of cancer patients. Fortunately, advanced development of bioinformatics helps us to identify cancers as a result from various alternations of biological and molecular factors, dysfunctional expression or mutation of genes, dysregulation of host immune responses, oxidative stress (the release of reactive oxygen species), injured effect of organs, activation of oncogenes or inactivation of suppressor genes, dysfunction and aberrant responses to growth factor, and cytokines to form the fertile tumor microenvironment (TME).14 Furthermore, interaction among genetic, epigenetic, and environmental factors also plays a role in tumorigenesis, contributing to the findings of small molecule-specific antitumor agents, which are available in modern cancer treatment.14 Among these, cells under repeated injuries and harmful insults without appropriately and precisely repairing processes have a tendency to transform to malignant cells, and additionally, if immunocompromised TME is present, invasive cancer is followed. Since all steps are required, just like successful implantation of seeds into greater floricultural soil (TME), an interruption of any point of this itinerary may delay or block the oncogenesis path. Therefore, it is rational to use targeted therapy to enhance tumor clearance ability by the immune system, to remove the fertile and rich contents from the TME, and to spoil the cancer cells for cancer treatment.15 Dr. Chen, the winner of the outstanding research for oncology, based on the abovementioned concept, attempted to administer the combination of anti–programmed cell death protein-1 (anti–PD-1) and multiple tyrosine kinase inhibitors (TKI) regimen for the therapy of heavily pretreated recurrent and/or metastatic head and neck squamous cell carcinoma patients.5 Their results are relatively impressive, including 4.6 months of progression-free survival and 6.2 months of overall survival of these 14 patients.5 Dr. Chen failed to find the positive correlation between PD-L1 expression and the treatment efficacy of anti–PD-1 inhibitors,5 which are useful in the prediction of the therapeutic effect of targeted agents, just like many other biomarkers.16 Moreover, adding multiple TKI to anti–PD-1 inhibitors also failed to overcome the immunotolerance status in the TME.5 Although the results seemed to be relatively disappointing, they provided us with a new thought that we should cross this parallel, critical, and big chasm shared by tumors themselves, TME, or both to obtain successful cancer therapy.
Basic oncology research winner is given to Dr. Chang for his excellent research focusing on the androgen receptor complex–associated protein (ARCAP) and exploring its role in the pathogenesis of hepatoma.6 Since hepatoma is a relatively male-predominant cancer and the sex disparities in hepatoma incidence or prevalence are noted, although the report showed that sex may not be an independent predictor of the outcomes of hepatocellular carcinoma patients, especially for those aged more than 50 years,17 the potential role of androgen receptor (AR) on tumorigenesis of liver (hematoma) can be easily expected. Dr. Chang’s group indeed identified a novel ARCAP as a co-activator to enhance the activity of AR, which may play an additional role to promote the malignant transformation of hepatocytes.6 Dr. Chang also cloned and mapped this ARCAP to Chromosome 1q23.2.6
Finally, we would like to introduce the 2021 top-cited article—wound healing, which has been published in the 2018 issue of the JCMA.7 As shown above, the circle of traumatic and repairing processes occurs at any time in all living organisms, which not only maintains the integrity of tissue, structure, or organs but also restores the normal and functional anatomy of living organisms.7 Fibrosis, scar, and even malignant transformation may be the products of the aberrant healing process. Therefore, a better and more thoroughly understanding of the detailed mechanisms of the healing process may accelerate a more advance in the regeneration medicine, which may provide a future chance to overcome the chronic disease–related organ damages and rejuvenate the aging process-related dysfunction of organs. With the help of healing and regeneration, it may significantly bring us back to a brand-new life in the near future.
This editorial is Part II containing a total of four researchers who have won the 2021 Outstanding Research Award from different fields, such as clinical and basic medicine, neurology, and oncology. All of them explore their professions to promote better patient’s care. We congratulate their success again and sincerely give a big invitation to all potential candidates and encourage them to submit their future works to the JCMA.
This article was supported by grants from the Taiwan Ministry of Science and Technology, Executive Yuan, Taiwan (MOST 110-2314-B-075-016-MY3 and MOST 111-2314-B-075-045), and Taipei Veterans General Hospital (V110C-082, and VGH111C-103). The authors appreciate the support from Female Cancer Foundation, Taipei, Taiwan.
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