Basic Medical Research Research Articles

Christopher Martin Dobson. 8 October 1949 — 8 September 2019

Christopher Martin Dobson was a distinguished biophysical chemist who earned an international reputation for his work on protein folding, misfolding and aggregation. Protein folding is a crucial process in biochemistry where a protein transitions from a disordered state to a structured, three-dimensional form after being synthesized by a ribosome. This transformation is essential for the protein to attain its biological functionality. The intricate folding pathway is guided by various interactions between amino acids within the protein chain. When protein folding goes awry, it can lead to misfolded proteins, which are associated with various disorders such as Alzheimer's and Parkinson's disease. The study of protein folding and misfolding has significant implications for both basic science and medical research. Chris's career spanned almost five decades, resulted in more than 870 publications and established a legacy that will influence the lives of many for decades to come. His outstanding mentorship resulted in some 100 of his former students and post-docs taking up independent positions at academic institutions in all parts of the world, while his research work has left a lasting imprint on the biophysical sciences and inspired an entire generation of research scientists.

Sensing DNA as danger: The discovery of cGAS

Insight into how the immune system recognizes and responds to pathogens had led to landmark advances in biology and medicine in the last decades. This year's Albert Lasker Award for Basic Medical Research honors Zhijian "James" Chen for the discovery of cGAS, the enzyme that senses foreign and "pathogenic" self-DNA-self-DNA aberrantly located in intracellular compartments. The definition of the cGAS-STING pathway opens new horizons for the understanding and treatment of human disease.

Discovery of cGAS as a DNA-Sensing Enzyme That Triggers Inflammation

In this Viewpoint, 2024 Albert Lasker Basic Medical Research Award winner Zhijian J. Chen describes his discovery of cyclic guanosine monophosphate–adenosine monophosphate synthase (cGAS), a DNA-sensing enzyme that triggers inflammation.

Hunting down the elusive cytosolic-DNA sensor

The 2024 Albert Lasker Basic Medical Research Award was attributed to Zhijian (James) Chen for “the discovery of the cGAS enzyme that senses foreign and self DNA, solving the mystery of how DNA stimulates immune and inflammatory responses.” Bringing to bear an ingenious in vitro complementation system, an astute insight, and superlative biochemistry, Chen and colleagues identified cGAS (cGAMP synthase) as both the molecule that perceives cytosolic DNA in infected, stressed, or dying cells and the enzyme that catalyzes the synthesis of cGAMP (cyclic GMP-AMP), a critical second messenger along the route to inflammatory cytokine production. These findings cleared up the reigning confusion surrounding a major mechanism of inciting the innate immune system, with therapeutic implications for fighting infections, containing tumors, and extinguishing autoimmune and inflammatory diseases.

An overview on the progress of cannabis in basic medical research

Cannabis, as an ancient plant, has a long history, in which it is rich in medicinal properties, but it also has many side effects. With studying cannabinoids and their receptors more and more deeply, the medicinal benefits of cannabis have been reported with a series of drug research and development and basic research. This article provides an overview of the pharmacological effects and basic research of cannabis, which included history of cannabis, character of plant, cultivation and exaction, pharmacology and treatment application, so as to provide a subsequent in-depth understanding on cannabis.

Physiological paradigm for assessing reward prediction and extinction using cortical direct current potential responses in rats

Anticipating positive outcomes is a core cognitive function in the process of reward prediction. However, no neurophysiological method objectively assesses reward prediction in basic medical research. In the present study, we established a physiological paradigm using cortical direct current (DC) potential responses in rats to assess reward prediction. This paradigm consisted of five daily 1-h sessions with two tones, wherein the rewarded tone was followed by electrical stimulation of the medial forebrain bundle (MFB) scheduled at 1000 ms later, whereas the unrewarded tone was not. On day 1, both tones induced a negative DC shift immediately after auditory responses, persisting up to MFB stimulation. This negative shift progressively increased and peaked on day 4. Starting from day 3, the negative shift from 600 to 1000 ms was significantly larger following the rewarded tone than that following the unrewarded tone. This negative DC shift was particularly prominent in the frontal cortex, suggesting its crucial role in discriminative reward prediction. During the extinction sessions, the shift diminished significantly on extinction day 1. These findings suggest that cortical DC potential is related to reward prediction and could be a valuable tool for evaluating animal models of depression, providing a testing system for anhedonia.

Could nerve transplantation be the future of this field: a bibliometric analysis about lumbosacral plexus injury.

Lumbosacral plexus injury is a highly distressing clinical issue with profound implications for patients' quality of life. Since the publication of the first relevant study in 1953, there has been very limited progress in basic research and clinical treatment in this field, and the developmental trajectory and research priorities in this field have not been systematically summarized using scientific methods, leaving the future direction of this research to be explored. Utilizing publications from the Web of Science (WoS) database, our research employed bibliometric methodology to analyze the fundamental components of publications, synthesize research trends, and forecast future directions. A total of 150 publications were included in our study, and the impressive advancement of research heat in this field can be attributed to the continuous increase in the number of papers, ranging from 14 papers in 2000 to 34 papers in 2023 over five years. Regarding the country, a central position in both quantity (H-index=125) and quality of publications (65 publications) is occupied by the United States, and close collaborations with other countries are observed. In terms of publication institutions, the highest number of publications (9 publications) is held by the Second Military Medical University. The journal with the most publications (5 publications) is the Journal of Trauma-Injury Infection and Critical Care. A pivotal role has been played by basic medical research in the development of this field. Concerning hotspots, the focus of the research core can be divided into three clusters (etiology, diagnosis and treatment; molecular, cells and mechanisms; physiology and pathology). This marks the inaugural bibliometric analysis of lumbosacral plexus injuries, offering a comprehensive overview of current publications. Our findings illuminate future research directions, international collaborations, and interdisciplinary relationships. Future research will emphasize clinical treatment and mechanism research, with a focus on sacral nerve stimulation and nerve transplantation.

Progress in study on animal models of trigeminal neuralgia.

Trigeminal neuralgia is a manifestation of orofacial neuropathic pain disorder, always deemed to be an insurmountable peak in the field of pain research and treatment. The pain is recurrent, abrupt in onset and termination similar to an electric shock or described as shooting. A poor quality of life has been attributed to trigeminal neuralgia, as the paroxysms of pain may be triggered by innocuous stimuli on the face or inside the oral cavity, such as talking, washing face, chewing and brushing teeth in daily life. The pathogenesis of trigeminal neuralgia has not been fully elucidated, although the microvascular compression in the trigeminal root entry zone is generally considered to be involved in the emergence and progression of the pain disorder. In addition, orofacial neuropathic pain restricted to one or more divisions of the trigeminal nerve might be secondary to peripheral nerve injury. Based on current hypotheses regarding the potential causes, a variety of animal models have been designed to simulate the pathogenesis of trigeminal neuralgia, including models of compression applied to the trigeminal nerve root or trigeminal ganglion, chronic peripheral nerve injury, peripheral inflammatory pain and center-induced pain. However, it has not yet been possible to determine which model can be perfectly employed to explain the mechanisms. The selection of appropriate animal models is of great significance for the study of trigeminal neuralgia. Therefore, it is necessary to discuss the characteristics of the animal models in terms of animal strains, materials, operation methods and behavior observation, in order to gain insight into the research progress in animal models of trigeminal neuralgia. In the future, animal models that closely resemble the features of human trigeminal neuralgia pathogenesis need to be developed, with the aim of making valuable contributions to the relevant basic and translational medical research.

Application of PROTACs in Target Identification and Target Validation.

PROTAC, as a novel therapeutic drug model, has received widespread attention from the academic and pharmaceutical industries. At the same time, PROTAC technology has led many researchers to focus on developing chemical biology tool properties due to its unique operating mechanism and protein dynamic regulatory properties. In recent years, the rapid development of PROTAC technology has gradually made it an essential tool for target identification and target validation. To further promote the application of PROTAC tools in drug discovery and basic medical sciences research, this review distinguished between target identification and target validation concepts. It summarized the research progress of PROTAC technology in these aspects.

Effect of Smoking on Cancer Surgery Outcomes and Recommendations for Perioperative Smoking Cessation Intervention

Smoking, a common behavior that causes health risks among adults around the world, is closely associated with the risks of developing various kinds of cancers. Nevertheless, the impact of smoking on preoperative risks and postoperative outcomes of cancer surgeries has been largely overlooked. Extensive basic medical and clinical research findings and prognosis data demonstrate that smoking is associated with increased risks of multiple perioperative complications, and that smoking affects the general prognosis of patients. Smoking cessation during the preoperative and perioperative periods effectively reduces these risks and improves the long-term postoperative outcomes of cancer patients. At present, health workers and patients are not giving adequate attention to smoking cessation interventions and the quality of interventions available is poor. Herein, we discussed the necessity of comprehensive and standardized smoking cessation services and made recommendations regarding the implementation of comprehensive and standardized smoking cessation services, providing support for cancer patients to access evidence-based care during the perioperative period.

Breaking the unvirtuous cycle: barriers and opportunities for research and development in Paraguay. A case study.

Medical research and development (R&D) is an undoubtedly relevant activity to drive innovation, improve healthcare policies and bring patients treatment opportunities for common and rare diseases. Equity and inclusion are matters of concern in research. High-income countries' research teams are more likely to have more impactful publications, grant funding, and clinical trials than middle or low-income countries. Low budget allocations to R&D and existing gaps in regulatory frameworks are some obstacles to growth. This unvirtuous cycle results in scarce advances in common endemic diseases and the underrepresentation of specific populations in innovative therapeutics research. We conducted a policy review and qualitative research to determine the principal characteristics of basic and clinical medical research in Paraguay, as well as barriers and facilitators to improve innovative R&D strategies in this country. To this aim, we examined published articles from 2005 to 2020, the organizational structure of national research agencies, the current regulation framework, and the composition and experience of local research groups and ethical review boards (ERBs). In addition, we performed semi-structured interviews to evaluate perceptions and expectations from different stakeholders, including investigators, ERBs members, sponsor associates, and Regulatory Agency executive staff. In 2018, Paraguay ranked 10th out of 12 South American countries in total number of publications and cumulative h-index score. Total Gross Domestic Product (GDP) allocation for R&D was 0.15%, ranking eighth out of 12 in the region. In 2021, the number of trials registered on ClinicalTrials.gov was 52, with only 16 ongoing recruiting studies at that time.Some of the main barriers identified included low incentives for academic careers and lack of experience in pharmaceutical research. An emergent necessity to develop a straight- forward normative framework was detected. Main facilitators included the development of two research initiative programs (PRONII and PROCIENCIA) from CONACYT (National Council of Science and Technology) which were associated with higher budget allocation and total number of publications in the 2011 to 2017 period. A total of six stakeholders participated in the semi-structured surveys. Interviewees highlighted the necessity of a centralized policy to promote R&D, which incorporates investigators and ERBs training, the development of standardized procedures, and the dissemination of research activities. Sponsor associates underlined that real-world evidence may represent a distinctive opportunity to enhance local research. Coordinated efforts are needed to break the unvirtuous cycle. There is an increasing interest in enhancing health research in Paraguay, materialized in the creation of specific programs that encourage the collaborative work of healthcare providers, basic scientists, and private investors. Nonetheless, a comprehensive approach is needed also to strengthen regulatory agencies and attract external sponsorship. While modern and currently popular topics, including artificial intelligence, real-world data, and translational research may represent key opportunities to seek investment, special policies should be adopted to prioritize research on the determinants of health in the Paraguayan population.

Quercetin-targeted AKT1 regulates the Raf/MEK/ERK signaling pathway to protect against doxorubicin-induced nephropathy in mice

BackgroundDoxorubicin is an anthracycline antitumor agent commonly used in clinical practice, which has some nephrotoxicity and is often used to establish mouse models of kidney injury for basic medical research. This study will investigate the protective effect of quercetin on renal function in doxorubicin-induced nephropathy mice. MethodsC57BL/6 mice were divided into control, model, and quercetin low-, and high-dose groups. Serum and urine were collected to analyze markers of kidney function. H&E staining was used to detect pathological changes in renal tissues. Transmission electron microscopy was performed to observe the ultrastructural changes in renal tissues. Immunohistochemistry was performed to detect the changes of Ang II. RT-qPCR was performed to detect the changes of cytokines. ELISA was used to detect changes in serum inflammatory factors. Molecular docking was performed to verify the targeting relationship between quercetin and AKT1. Western blot was performed to detect Bax, Bcl-2, Cyt-c, AKT1, Raf, MEK, and ERK proteins. ResultsQuercetin could induce the recovery of kidney function in kidney-injured mice; H&E results showed that kidney tissue damage and tissue fibrosis were reduced in kidney-injured mice under quercetin. The mitochondrial swollen structure was destroyed by doxorubicin, while the mitochondrial structure was restored under quercetin. The levels of abnormal apoptotic proteins Bax and Bcl-2 were regulated to normal by quercetin. The high expression of Ang II caused by doxorubicin was down-regulated by quercetin. Abnormal inflammatory factors caused by doxorubicin were reversed by quercetin. Western blot experiments showed that quercetin regulated the protein levels of AKT1 and Raf/MEK/ERK and inhibited the detrimental effects of doxorubicin. ConclusionQuercetin may mitigate doxorubicin-induced kidney injury in mice by regulating renal cell inflammatory factors and Raf/MEK/ERK signaling pathway through AKT1 to promote recovery of renal function.

Analysis of Fecal Microbiota in Patients with Hypertension Complicated with Ischemic Stroke.

Ischemic stroke is a disease with a very high incidence in the clinic, and hypertension is the most important variable risk factor of ischemic stroke. Studies have shown that intestinal microbes are involved in the occurrence and development of various diseases. This study aims to explore whether intestinal microbes play an important role in the pathogenesis of ischemic stroke in a hypertensive population. In this study, the inpatients in the Department of Neurology and Cardiology of the Second Affiliated Hospital of Shandong First Medical University in April 2021 were selected, including seven patients with hypertension complicated with ischemic stroke and only seven patients with hypertension. After collecting the stool samples of patients, the gene sequence of the samples was detected by 16S rRNA sequencing technology, and the double-ended 2 × 150bp sequencing was carried out. After sequencing, the results were analyzed by diversity analysis, species difference analysis, species function difference analysis, and other bioinformatics tests. According to the test results, serum proteomics and biochemical blood tests were carried out to verify. There was no significant difference in α diversity and β diversity between hypertension complicated with the cerebral infarction and hypertension groups. LEfSe analysis showed that at the genus level, compared with the hypertension group, Bacteroides, UCG_009, and Eisenbergiella had significantly increased relative abundance. The genera with relatively significantly reduced abundance are Ruminococcus_gnavus_group, Sutterellaceae, Burkholderia, and Prevotella and the LDA score of Prevotella is < - 4, which indicates that there are significant differences. Compared with the blood biochemical indexes, the results showed that the level of APOA1 in hypertensive patients with ischemic stroke was significantly higher than that in hypertensive patients (p < 0.05), but there was no significant difference in total cholesterol (CHOL), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), apolipoprotein B (APOB), and free fatty acid (NEFA). Proteomic analysis showed that there were 89 up-regulated genes and 51 down-regulated genes in the serum of the two groups, and the expression of APOC2 and APOC3 in the cerebral infarction group with hypertension was significantly higher than that in the hypertension group (p < 0.05). The intestinal diversity of patients with hypertension complicated with stroke is similar to that of patients with hypertension, but there are differences in microbiota, among which Prevotella is the most significant. Prevotella could affect lipid metabolism so that APOC2 and APOC3 in the blood are significantly increased, leading to cerebral artery atherosclerosis and, finally, ischemic stroke. This provides a new idea for preventing and treating ischemic stroke in patients with hypertension, but the mechanism of Prevotella acting on apolipoprotein needs further verification by basic medical research.

Starting at Go: Protein structure prediction succumbs to machine learning

This year’s Albert Lasker Basic Medical Research Award recognizes the invention of AlphaFold, a revolutionary advance in the history of protein research which for the first time offers the practical ability to accurately predict the three-dimensional arrangement of amino acids in the vast majority of proteins on a genomic scale on the basis of sequence alone [J. Jumper et al., Nature 596, 583–589 (2021) and K. Tunyasuvunakool et al., Nature 596, 590–596 (2021)]. This extraordinary achievement by Demis Hassabis and John Jumper and their coworkers at Google’s DeepMind and other collaborators was built on decades of experimental protein structure determination (structural biology) as well as the gradual development of multiple strategies incorporating biologically inspired statistical approaches. But when Jumper and Hassabis added a brew of innovative neural network-based machine learning approaches to the mix, the results were explosive. Realizing the half-century-old dream of predicting protein structure has already accelerated the pace and creativity of many areas of Chemistry, Biology, and Medicine.

Neuroprotective effects of trehalose following middle cerebral artery occlusion in rats

BackgroundIschemic stroke remains one of the leading causes of mortality and disability in the population. Middle cerebral artery occlusion (MCAO) followed by reperfusion is widely accepted to mimic stroke in basic medical research. Trehalose is a non-reducing disaccharide compound found naturally in most organisms such as bacteria, yeasts, invertebrates and even in plants except for vertebrates. Its protective role has been shown in various neurological disorders. In the current study, the MCAO model was used to investigate the therapeutic efficacy of trehalose. MethodsIn this experimental study, 32 Male Wistar rats were subjected to MCAO following 24 h of reperfusion. Wistar rats were randomly divided into four groups: Sham-operated control group (Sham), middle cerebral artery occlusion (MCAO) group, trehalose (50 and 100 mg/kg) treatment + MCAO groups. Trehalose was intraperitoneally injected 3- and 6 h post-ischemia. After 24 h of reperfusion and evaluation of the intensity of neurological dysfunction via a modified Rogers scale, the brains were removed and the volume of ischemia was stained using 2,3,5-triphenyl tetrazolium chloride. ResultsCompared with the control group, trehalose administration with dosages of 50 and 100 mg/kg significantly decreased the modified Rogers score (p<0.01 and p<0.001, respectively) and reduced the volume of ischemia (p<0.05 and p<0.001, respectively). ConclusionTrehalose in the MCAO model has a protective effect. The findings of the current study suggest that trehalose can be a potential therapeutic option in ischemic strokes; however, this study was preliminary and further studies are needed.

Worldwide productivity and research trend of publications concerning tumor immune microenvironment (TIME): a bibliometric study

BackgroundAs the complexity and diversity of the tumor immune microenvironment (TIME) are becoming better understood, burgeoning research has progressed in this field. However, there is a scarcity of literature specifically focused on the bibliometric analysis of this topic. This study sought to investigate the development pattern of TIME-related research from 2006 to September 14, 2022, from a bibliometric perspective.MethodsWe acquired both articles and reviews related to TIME from the Web of Science Core Collection (WoSCC) (retrieved on September 14, 2022). R package “Bibliometrix” was used to calculate the basic bibliometric features, present the collaborative conditions of countries and authors, and generate a three-field plot to show the relationships among authors, affiliations, and keywords. VOSviewer was utilized for co-authorship analysis of country and institution and keyword co-occurrence analysis. CiteSpace was used for citation burst analysis of keywords and cited references. In addition, Microsoft Office Excel 2019 was used to develop an exponential model to fit the cumulative publication numbers.ResultsA total of 2545 publications on TIME were included, and the annual publication trend exhibited a significant increase over time. China and Fudan University were the most productive country and institution, with the highest number of publications of 1495 and 396, respectively. Frontiers in Oncology held the highest number of publications. A number of authors were recognized as the main contributors in this field. The clustering analysis revealed six clusters of keywords that highlighted the research hot spots in the fields of basic medical research, immunotherapy, and various cancer types separately.ConclusionsThis research analyzed 16 years of TIME-related research and sketched out a basic knowledge framework that includes publications, countries, journals, authors, institutions, and keywords. The finding revealed that the current research hot spots of the TIME domain lie in “TIME and cancer prognosis”, “cancer immunotherapy”, and “immune checkpoint”. Our researchers identified the following areas: “immune checkpoint-based immunotherapy”, “precise immunotherapy” and “immunocyte pattern”, which may emerge as frontiers and focal points in the upcoming years, offering valuable avenues for further exploration.

The role of metformin in the management of endometriosis: A systematic review and meta-analysis

Purpose: To analyze the activity of metformin in endometriosis, with a view to alleviating disease progression.&#x0D; Methods: A search was conducted using electronic databases such as CNKI, VIP, CBM, WANFANG, Embase, PubMed, Cochrane, and Web of Science from January 1980 to January 2022 for randomized trials involving any intrapartum fetal surveillance method. A network meta-analysis was performed within a frequentist framework, and it was assessed for quality and network inconsistency of the trials. A ninety-five percent confidence interval (CI) was used to report the relationship between metformin levels and patients with endometriosis.&#x0D; Results: Eight eligible studies which included 688 patients were evaluated in this meta-analysis. The primary indicators were treatment efficiency and CA-125 level. Metformin significantly increased treatment efficiency (SMD = 3.29, 95 % CI 2.01, 5.40, p &lt; 0.00001). As expected, metformin also reduced the CA-125 level in endometriosis patients as a result (Odds Ratio, OR = -1.20, 95 % CI: -1.40 - 1.00, p &lt; 0.00001).&#x0D; Conclusion: Metformin alleviates pains caused by endometriosis. However, some studies had scanty information about alleviating clinical symptoms other than basic medical research. More randomized controlled trials are needed to confirm treatment efficacy.

Role of hypoxia inducible factor HIF-1α in heart valves.

The 2016 Albert Lasker Basic Medical Research Award and subsequently the 2019 Nobel Prize in Physiology or Medicine were awarded to William Kaelin, Jr., Sir Peter Ratcliffe, and Gregg Semenza for their work on how cells sense and adapt to hypoxic conditions. Their work showed that the changes in gene expression, cell metabolism, and tissue remodelling that occur in response to low oxygen concentrations are orchestrated by the transcription factor, hypoxia inducible factor-1α (HIF-1α). While the effects mediated by HIF-1α have been widely studied, its role in heart valves has only recently been investigated. These studies have shown that HIF-1α expression is evident in mechanisms that regulate the structure and function of heart valves. These include embryonic development, the regulation of the extracellular matrix, angiogenesis and the initiation of the calcification process. This review provides a background on the role and function of HIF-1α in response to hypoxia and a discussion of the available evidence of its involvement in the regulation of heart valves in health and disease.

Current understanding of the cardiotoxicity-related treatment of immune checkpoint inhibitors in breast cancer

Immune Checkpoint Inhibitors (ICIs) as the most important and widely used currently, have changed the traditional approach to cancer treatment and significantly improved the prognosis of most patients with advanced malignancies. Breast cancer is the most dangerous threatening tumor to women’s health and life globally, ICIs have shed light on the treatment for refractory breast cancer subtypes, including Triple-Negative Breast Cancer (TNBC) and trastuzumab resistance of human epidermal growth factor receptor 2 positives (HER2+). However, immune-related adverse events (irAE) associated with ICIs bring many extra considerations. Among these, potential cardiotoxicity is rarely seen but with the highest fatality rate. In the present review, we introduced the ICIs approved for the treatment of breast cancer and brief guideline for clinical application. Then we briefly summarized ICIs-related cardiotoxicity in breast cancer and mechanism based on immunology and basic medical research. Furthermore, we make a brief summary of the diagnosis methods.

Evaluating the Effects of Cryopreservation on the Viability and Gene Expression of Porcine-Ear-Skin Fibroblasts.

Owing to the inherent heterogeneity and plasticity of fibroblasts, they are considered as the conventional biological resources for basic and clinical medical research. Thus, it is essential to generate knowledge about the establishment of fibroblast cultures and the effects of cryopreservation processes on their biological characteristics. Since the pig (Sus scrofa) possesses numerous genetic, physiological, and anatomical similarities with humans, porcine fibroblasts are naturally regarded as useful analogues of human fibroblasts. Nonetheless, less attention has been given to the alterations in viability and gene expression of cryopreserved porcine fibroblasts. In this study, we aimed to obtain fibroblasts from porcine ear skin and evaluate the effects of cryopreservation on the cell survival, proliferation, and gene expression profiles of the fibroblasts by trypan-blue-staining assay, Cell Counting kit-8 (CCK-8) assay, and RNA-sequencing analysis, respectively. Our results suggested that morphologically stable fibroblast cultures can be constructed from pig-ear skin. The post-thaw survival rate of the cryopreserved fibroblasts at 0 h and 24 h was over 90%. The proliferative activity of the cryopreserved fibroblasts was similar to that of the non-cryopreserved fibroblasts after 7 days of in vitro culture, which suggested that cryopreservation did not influence the viability. The RNA-sequencing analysis indicated that this should be attributed to the 867 differentially expressed genes (DGEs) identified, which are involved in molecular process related to cell recovery and survival after cryo-stimulation. In addition, eight important DEGs BMP2, GDF15, EREG, AREG, HBEGF, LIF, IL-6, and HOX-7 could potentially be applied to improve the efficiency of fibroblast cryopreservation, but comprehensive and systematic studies on understanding the underlying mechanisms responsible for their modulatory roles are urgently needed.