Role of interferon-induced transmembrane protein family in cancer progression: a special focus on pancreatic cancer.

Human interferon-induced transmembrane protein family (IFITMs) consists of five main proteins. IFITM1, IFITM2, and IFITM3 can be induced by interferon, while IFITM5 and IFITM10 are insensitive to interferon. IFITMs has various functions, including well-researched antiviral effects. As a molecule whose expression is significantly increased by interferon in the immune microenvironment, IFITMs has drawn growing interest in recent years for their role in the cancer progression. Unlike antiviral effects, the role and mechanism of IFITMs in cancer progression have not been clearly studied, especially the role and molecular mechanism of IFITMs in pancreatic cancer are rarely reported in the literature. This article focuses on the role and potential mechanism of IFITMs in pancreatic cancer progression by analyzing the function and mechanism of IFITM1-3 in other cancers and conducting bioinformatics analysis using the databases, so as to provide a new target for pancreatic cancer therapy.

Phytohemagglutinin from Phaseolus vulgaris enhances the lung cancer cell chemotherapy sensitivity by changing cell membrane permeability.

Chemotherapy is still a prevalent strategy for clinical lung cancer treatment. However, the inevitable emerged drug resistance has become a great hurdle to therapeutic effect. Studies have demonstrated that the primary cause of drug resistance is a decrease in the chemotherapeutic medicine concentration. Several lectins have been confirmed to be effective as chemotherapy adjuvants, enhancing the anti-tumor effects of chemotherapy drugs. Here, we combined phytohemagglutinin (PHA), which has been reported possess anti-tumor effects, with chemotherapy drugs Cisplatin (DDP) and Adriamycin (ADM) on lung cancer cells to detect the sensitivities of PHA as a chemotherapy adjuvant. Our results demonstrated that the PHA significantly enhanced the sensitivity of lung cancer cells to DDP and ADM, and Western blot showed that PHA combined with DDP or ADM enhance cytotoxic effects by inhibiting autophagy and promoting apoptosis. More importantly, we found PHA enhanced the chemotherapeutic drugs cytotoxicity by changing the cell membrane to increase the intracellular chemotherapeutic drugs concentration. Besides, the combination of PHA and ADM increased the ADM concentration in the multidrug-resistant strain A549-R cells and achieved the drug sensitization effect. Our results suggest that PHA combined with chemotherapy can be applied in the treatment of lung cancer cells and lung cancer multidrug-resistant strains, and provide a novel strategy for clinical tumor chemotherapy and a new idea to solve the problem of drug resistance in clinical lung cancer.

Recombinant Phaseolus vulgaris phytohemagglutinin L-form expressed in the Bacillus brevis exerts in vitro and in vivo anti-tumor activity through potentiation of apoptosis and immunomodulation.

Leukocyte phytohemagglutinin (PHA-L) is a tetrameric isomer of phytohemagglutinin (PHA) purified from the red kidney bean (Phaseolus vulgaris) and is a well-known human lymphocyte mitogen. Due to its antitumor and immunomodulatory effects, PHA-L may serve as a potential antineoplastic agent in future cancer therapeutics. However, various negative consequences of PHA have been reported in the literature as a result of the restricted acquisition methods, including oral toxicity, hemagglutinating activity, and immunogenicity. There is a critical need to explore a new method to obtain PHA-L with high purity, high activity and low toxicity. In this report active recombinant PHA-L protein was successfully prepared by Bacillus brevius expression system, and the antitumor and immunomodulatory activities of recombinant PHA-L were characterized by in vitro and in vivo experiments. The results showed that recombinant PHA-L protein had stronger antitumor effect, and its anti-tumor mechanism was realized through direct cytotoxicity and immune regulation. Importantly, compared with natural PHA-L, the recombinant PHA-L protein showed the lower erythrocyte agglutination toxicity in vitro and immunogenicity in mice. Altogether, our study provides a new strategy and important experimental basis for the development of drugs with dual effects of immune regulation and direct antitumor activity.

Preparation of a novel monoclonal antibody against active components of PHA-L from Phaseolus vulgaris and its functional characteristics.

BACKGROUND: Leukocyte phytohemagglutinin (PHA-L), derived from the L4 tetramer of PHA, has been frequently employed as a mitogen to induce T lymphocyte proliferation in vitro. The biological application of PHA-L in cancer diagnosis and treatment has gained traction in recent years. However, it has been noted that PHA-L obtained using traditional procedures has a massive amount of impurities or toxic components, which interfere with the activity of PHA-L. Preparation of a monoclonal antibody against active PHA-L is a significant tool for studying PHA-L's function and therapeutic potential. RESULTS: We successfully prepared monoclonal antibodies against the active components of PHA-L based on the whole PHA-L protein as an antigen, and found that monoclonal antibody 3C1C6G11 can be employed in western blot, immunofluorescence, and immunohistochemistry detection. Importantly, preliminary result shows that the mAb 3C1C6G11 may prevent PHA-L-induced cell aggregation and AICD (activation-induced cell death). CONCLUSIONS: The monoclonal antibody mAb 3C1C6G11 prepared in this study can be used as an effective tool for detecting PHA-L active components, investigating PHA-L's function and antineoplastic application.

Neurological Symptoms and Their Associations With Inflammatory Biomarkers in the Chronic Phase Following Traumatic Brain Injuries.

Background: The underlying biological mechanisms for neurological symptoms following a traumatic brain injury (TBI) remain poorly understood. This study investigated the associations between serum inflammatory biomarkers and neurological symptoms in the chronic phase following moderate to severe TBI. Methods: The serum interleukin [IL]-1ß, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, and the tumor necrosis factor [TNF]-α in 72 TBI patients 6 months to 2 years post injury were measured. Neurological symptoms including depression, chronic headache, sleep disturbance, irritability, anxiety, and global neurological disability was assessed. The associations between the biomarkers and the neurological symptoms were assessed using correlation and regression analysis. Results: It was found that the most common post-injury symptom was sleep disturbance (84.7%), followed by chronic headaches (59.7%), irritability (55.6%), and depression (54.2%). TNF-α was a protective factor for chronic headache (OR = 0.473, 95% CI = 0.235-0.952). IL-6 was positively associated with sleep disturbance (r = 0.274, p = 0.021), while IL-5 and IL-12p70 were negatively associated with the degree of global neurological disability (r = -0.325, p = 0.006; r = -0.319, p = 0.007). Conclusion: This study provides preliminary evidence for the association between chronic inflammation with neurological symptoms following a TBI, which suggests that anti-inflammatory could be a potential target for post-TBI neurological rehabilitation. Further research with larger sample sizes and more related biomarkers are still needed, however, to elucidate the inflammatory mechanisms for this association.

Phylogenomics of the genus Glycine sheds light on polyploid evolution and life-strategy transition.

Polyploidy and life-strategy transitions between annuality and perenniality often occur in flowering plants. However, the evolutionary propensities of polyploids and the genetic bases of such transitions remain elusive. We assembled chromosome-level genomes of representative perennial species across the genus Glycine including five diploids and a young allopolyploid, and constructed a Glycine super-pangenome framework by integrating 26 annual soybean genomes. These perennial diploids exhibit greater genome stability and possess fewer centromere repeats than the annuals. Biased subgenomic fractionation occurred in the allopolyploid, primarily by accumulation of small deletions in gene clusters through illegitimate recombination, which was associated with pre-existing local subgenomic differentiation. Two genes annotated to modulate vegetative-reproductive phase transition and lateral shoot outgrowth were postulated as candidates underlying the perenniality-annuality transition. Our study provides insights into polyploid genome evolution and lays a foundation for unleashing genetic potential from the perennial gene pool for soybean improvement.

Genetic variant rs3750625 in the 3'UTR of ADRA2A affects stress-dependent acute pain severity after trauma and alters a microRNA-34a regulatory site.

α2A adrenergic receptor (α2A-AR) activation has been shown in animal models to play an important role in regulating the balance of acute pain inhibition vs facilitation after both physical and psychological stress. To our knowledge, the influence of genetic variants in the gene encoding α2A-AR, ADRA2A, on acute pain outcomes in humans experiencing traumatic stress has not been assessed. In this study, we tested whether a genetic variant in the 3'UTR of ADRA2A, rs3750625, is associated with acute musculoskeletal pain (MSP) severity following motor vehicle collision (MVC, n = 948) and sexual assault (n = 84), and whether this influence was affected by stress severity. We evaluated rs3750625 because it is located in the seed binding region of miR-34a, a microRNA (miRNA) known to regulate pain and stress responses. In both cohorts, the minor allele at rs3750625 was associated with increased musculoskeletal pain in distressed individuals (stress*rs3750625 P = 0.043 for MVC cohort and P = 0.007 for sexual assault cohort). We further found that (1) miR-34a binds the 3'UTR of ADRA2A, (2) the amount of repression is greater when the minor (risk) allele is present, (3) miR-34a in the IMR-32 adrenergic neuroblastoma cell line affects ADRA2A expression, (4) miR-34a and ADRA2A are expressed in tissues known to play a role in pain and stress, (5) following forced swim stress exposure, rat peripheral nerve tissue expression changes are consistent with miR-34a regulation of ADRA2A. Together, these results suggest that ADRA2A rs3750625 contributes to poststress musculoskeletal pain severity by modulating miR-34a regulation.

Prevalence of depressive symptoms and its correlates among medical students in China: a national survey in 33 universities.

We conducted a national survey among medical students in China to estimate the prevalence of depressive symptoms and explore associated risk factors based on an established questionnaire composed of demographic information, life events in the past four weeks before survey, and the validated Chinese version of the 21-item Beck's Depression Inventory (BDI). The mean age of enrolled 9010 students was 20.7 (standard deviation: 1.6) years. BDI scores indicated that 19.9% had depressive symptoms based on the cut-off score of 14. Socioeconomic factors and student characteristics such as male sex, low monthly income per capita, father's poor education background, and higher year of study were associated with higher prevalence of depressive symptoms among medical students. Students who studied in comprehensive universities were more likely to have depressive symptoms compared with those from medical universities. Habitual smoking and alcohol drinking, sleep deprivation, and hospitalization or medication for one week or more in the last four weeks also predisposed students to higher risk of depressive symptoms. Our results indicate that depressive symptoms are becoming a highly prevalent health problem among Chinese medical students. Primary and secondary prevention should be prioritized to tackle this issue based on potential risk factors.

The androgen receptor gene polyglycine repeat polymorphism is associated with memory performance in healthy Chinese individuals.

Cognitive functions such as memory are quantitative traits in human, and have both genetic and environmental influences. Testosterone has been implicated in the modulation of memory function. Therefore, genetic variation which influences testosterone signaling may modulate memory function. The principal receptor for testosterone is the androgen receptor, the gene for which maps to the X chromosome. In the present study, we hypothesized that common variation in two functional polymorphisms in the androgen receptor gene, the polyglutamine (CAG) and/or polyglycine (GGN) repeats, would influence memory function in healthy subjects. Variation in length of either repeat modulates the function of the AR gene, either by changing the amount of protein produced, by altering transactivation of the receptor or by producing toxic polyglycine or polyglutamine fragments. In order to test this hypothesis, we analyzed 449 healthy Chinese individuals. CAG repeats were not associated with memory performance. However we observed a significant association between GGN repeats and Immediate Logical Memory (chi(2)=23.6, d.f.=7, p=0.001) and Delayed Logical Memory (chi(2)=16.3, d.f.=7, p=0.022). The association of GGN repeats with Immediate Logical Memory remained significant after 6000 permutation corrections (p=0.013). There was also a sex difference, as association between GGN repeats and memory was observed only in females (p=0.002 for Immediate and p=0.014 for Delayed Logical Memory), but not in males (p=0.31 and 0.83, respectively). We conclude that functional variation of the androgen receptor gene is able to modulate memory function in women.