CD44s and CD44v8-10 isoforms confer acquired resistance to osimertinib by activating the ErbB3/STAT3 signaling pathway.

AIMS: Although epidermal growth factor receptor (EGFR)-mutant lung cancers respond well to osimertinib, acquired resistance to osimertinib eventually develops through EGFR-dependent and EGFR-independent resistance mechanisms. CD44 splicing variants are widely expressed in lung cancer tissues. However, it remains unclear whether specific splicing variants are involved in acquired resistance to osimertinib. MAIN METHODS: The real-time PCR was performed to measure the expression levels of total CD44 and specific CD44 splicing variants (CD44s or CD44v). Gene knockdown and restoration were performed to investigate the effects of CD44 splicing variants on osimertinib sensitivity. Activation of the signaling pathway was evaluated using receptor-tyrosine-kinase phosphorylation membrane arrays, co-immunoprecipitation, and western blotting. KEY FINDINGS: Clinical analysis demonstrated that the expression level of total CD44 increased in primary cancer cells from lung adenocarcinomas patients after the development of acquired resistance to osimertinib. Furthermore, osimertinib-resistant cells showed elevated levels of either the CD44s variant or CD44v variants. Manipulations of CD44s or CD44v8-10 were performed to investigate their effects on treatment sensitivity to osimertinib. Knockdown of CD44 increased osimertinib-induced cell death in osimertinib-resistant cells. However, restoration of CD44s or CD44v8-10 in CD44-knockdown H1975/AZD-sgCD44 cells induced osimertinib resistance. Mechanically, we showed that ErbB3 interacted with CD44 and was transactivated by CD44, that consequently triggered activation of the ErbB3/STAT3 signaling pathway and led to CD44s- or CD44v8-10-mediated osimertinib resistance. SIGNIFICANCE: CD44 is a co-receptor for ErbB3 and triggers activation of the ErbB3 signaling axis, leading to acquired resistance to osimertinib. CD44/ErbB3 signaling may represent a therapeutic target for overcoming osimertinib resistance.

miR-204 suppresses cancer stemness and enhances osimertinib sensitivity in non-small cell lung cancer by targeting CD44.

Osimertinib is an effective treatment option for patients with advanced non-small cell lung cancer (NSCLC) with EGFR activation or T790M resistance mutations; however, acquired resistance to osimertinib can still develop. This study explored novel miRNA-mRNA regulatory mechanisms that contribute to osimertinib resistance in lung cancer. We found that miR-204 expression in osimertinib-resistant lung cancer cells was markedly reduced compared to that in osimertinib-sensitive parental cells. miR-204 expression levels in cancer cells isolated from treatment-naive pleural effusions were significantly higher than those in cells with acquired resistance to osimertinib. miR-204 enhanced the sensitivity of lung cancer cells to osimertinib and suppressed spheroid formation, migration, and invasion of lung cancer cells. Increased miR-204 expression in osimertinib-resistant cells reversed resistance to osimertinib and enhanced osimertinib-induced apoptosis by upregulating BIM expression levels and activating caspases. Restoration of CD44 (the direct downstream target gene of miR-204) expression reversed the effects of miR-204 on osimertinib sensitivity, recovered cancer stem cell and mesenchymal markers, and suppressed E-cadherin expression. The study demonstrates that miR-204 reduced cancer stemness and epithelial-to-mesenchymal transition, thus overcoming osimertinib resistance in lung cancer by inhibiting the CD44 signaling pathway.

Association of Matrix Metalloproteinase-1 Promoter Polymorphisms With Asthma Risk.

BACKGROUND/AIM: Matrix metalloproteinase-1 (MMP-1) expression has been documented as an influential contributor to the intricate milieu of allergic airway inflammation, tissue remodeling, and the exacerbation of asthma's severity. However, the genetic role underlying MMP-1 in the context of asthma has remained enigmatic, with its full implications yet to be unveiled. Considering this, our research was designed to investigate the association of MMP-1 -1607 rs1799750 and the propensity for asthma severity. PATIENTS AND METHODS: As a case-control investigation, our study enrolled 198 individuals diagnosed with asthma and age- and sex-matched 453 non-asthmatic controls. The genotypes of MMP-1 rs1799750 were determined utilizing the polymerase chain reaction-restriction fragment length polymorphism methodology. RESULTS: The frequency distributions of 2G/2G, 1G/2G and 1G/1G genotypes at MMP-1 rs1799750 were 49, 42.9, and 8.1%, respectively, among the patients with asthma. This pattern was not different from that of controls (43.7, 46.8, and 9.5%, respectively) (p for trend=0.4486). The allelic frequency pertaining to the variant 1G allele within the asthma group was 29.5%, with a non-significant disparity compared to the 32.9% in the control group (p=0.2596). Noticeably, there was a positive association between MMP-1 rs1799750 2G/1G and 1G/1G genotypes with asthma severity (p=0.0060). CONCLUSION: Our research indicated that the presence of MMP-1 rs1799750 1G allele might not be the sole arbiter of an individual's susceptibility to asthma, yet its potential to function as a discerning prognostic marker for the severity of asthma emerged as a noteworthy finding deserving attention and further exploration.

Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.

As a key immune cell in the brain, microglia are essential for protecting the central nervous system (CNS) from viral infections, including HIV. Microglia possess functional Toll-like receptor 3 (TLR3), a key viral sensor for activating interferon (IFN) signaling pathway-mediated antiviral immunity. We, therefore, studied the effect of poly (I:C), a synthetic ligand of TLR3, on the activation of the intracellular innate immunity against HIV in human iPSC-derived microglia (iMg). We found that poly (I:C) treatment of iMg effectively inhibits HIV infection/replication at both mRNA and protein levels. Investigations of the mechanisms revealed that TLR3 activation of iMg by poly (I:C) induced the expression of both type I and type III IFNs. Compared with untreated cells, the poly (I:C)-treated iMg expressed significantly higher levels of IFN-stimulated genes (ISGs) with known anti-HIV activities (ISG15, MxB, Viperin, MxA, and OAS-1). In addition, TLR3 activation elicited the expression of the HIV entry coreceptor CCR5 ligands (CC chemokines) in iMg. Furthermore, the transcriptional profile analysis showed that poly (I:C)-treated cells had the upregulated IFN signaling genes (ISG15, ISG20, IFITM1, IFITM2, IFITM3, IFITM10, APOBEC3A, OAS-2, MxA, and MxB) and the increased CC chemokine signaling genes (CCL1, CCL2, CCL3, CCL4, and CCL15). These observations indicate that TLR3 is a potential therapy target for activating the intracellular innate immunity against HIV infection/replication in human microglial cells. Therefore, further studies with animal models and clinical specimens are necessary to determine the role of TLR3 activation-driven antiviral response in the control and elimination of HIV in infected host cells.

LncRNA SLCO4A1-AS1 suppresses lung cancer progression by sequestering the TOX4-NTSR1 signaling axis.

BACKGROUND: Metastasis is a multistep process involving the migration and invasion of cancer cells and is a hallmark of cancer malignancy. Long non-coding RNAs (lncRNAs) play critical roles in the regulation of metastasis. This study aims to elucidate the role of the lncRNA solute carrier organic anion transporter family member 4A1-antisense 1 (SLCO4A1-AS1) in metastasis and its underlying regulatory mechanisms. METHODS: A comprehensive analysis of the Gene Expression Omnibus (GEO) database were used to identify metastasis-associated lncRNAs. Transwell migration and invasion assays, and a tail vein-injection mouse model were used to assess the migration and invasion of cancer cells in vitro and in vivo, respectively. High-throughput screening methods, including MASS Spectrometry and RNA sequencing (RNA-seq), were used to identify the downstream targets of SLCO4A1-AS1. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), western blotting, RNA pull-down, RNA immunoprecipitation (RIP), fluorescence in situ hybridization (FISH), and chromatin immunoprecipitation (ChIp) assays were conducted to identify and validate the underlying regulatory mechanisms of SLCO4A1-AS1. RESULTS: SLCO4A1-AS1 reduced cancer cell migration and invasion by disrupting cytoskeleton filaments, and was associated with longer overall survival in patients with lung adenocarcinoma. SLCO4A1-AS1 directly interacted with the DNA-binding protein, TOX High Mobility Group Box Family Member 4 (TOX4), to inhibit TOX4-induced migration and invasion. Furthermore, RNA-seq revealed that neurotensin receptor 1 (NTSR1) is a novel and convergent downstream target of SLCO4A1-AS1 and TOX4. Mechanistically, SLCO4A1-AS1 functions as a decoy of TOX4 by interrupting its interaction with the NTSR1 promoter and preventing NTSR1 transcription. Functionally, NTSR1 promotes cancer cell migration and invasion through cytoskeletal remodeling, and knockdown of NTSR1 significantly inhibits TOX4-induced migration and invasion. CONCLUSION: These findings demonstrated that SLCO4A1-AS1 antagonizes TOX4/NTSR1 signaling, underscoring its pivotal role in lung cancer cell migration and invasion. These findings hold promise for the development of novel therapeutic strategies targeting the SLCO4A1-AS1/TOX4/NTSR1 axis as a potential avenue for effective therapeutic intervention in lung cancer.

Assembly and co-occurrence patterns of rhizosphere bacterial communities are closely linked to soil fertility during continuous cropping of cut chrysanthemum (Chrysanthemum morifolium Ramat).

AIMS: Continuous cropping is known to have profound effects on the soil microbial community in different planting systems. However, we lack an understanding of how different years of continuous cropping affects rhizosphere soil bacterial community co-occurrence pattern and assembly processes in the cut chrysanthemum (Chrysanthemum morifolium Ramat.) field. METHODS AND RESULTS: We collected the soils from cut chrysanthemum rhizospheres with planting for 1 year (PY1) and continuous cropping for 6 years (CY6) and 12 years (CY12). Real-time quantitative PCR and flow cytometry (FCM) techniques were used to test the 16S rRNA gene copy number and bacterial cell count, respectively. The bacterial community structure was analysed by using high-throughput sequencing technology. The CY12 had a significantly decreased soil fertility index and rhizosphere bacterial living cell counts and gene copy numbers compared to CY6 and PY1 (P < 0.05). The rhizosphere bacterial community dissimilarity increased as the continuous cropping years increased. Three main ecological clusters (modules #1, #2, and #3) were observed in the bacterial co-occurrence network across all samples, and only the relative abundance of module #1 (enriched in the CY12) was significantly correlated with soil fertility (P < 0.05). Moreover, the rhizosphere bacterial community assembly was primarily governed by the deterministic process under 12 years of continuous cropping. CONCLUSIONS: Soil fertility decline correlates with ecological network modularization and the deterministic assembly process of the rhizosphere bacterial community of cut chrysanthemum during continuous cropping.

Preliminary proteomic analysis of human tears in lacrimal adenoid cystic carcinoma and pleomorphic adenoma.

AIM: To detect proteomic differences in tears between adenoid cystic carcinoma (ACC) and pleomorphic adenoma (PA). METHODS: Tear samples were collected from 4 patients with ACC, 5 with PA, and 4 control cases. Label-free analysis and parallel reaction monitoring (PRM) were used to screen and validate the tear proteome. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted for bioinformatics analysis. RESULTS: In total, 1059 proteins in tear samples were identified by label-free analysis. Between ACC and PA, 415 differentially expressed proteins were detected. Based on the GO annotation, enzyme regulator activity and serine-type endopeptidase inhibitor activity in the molecular function category, blood microparticle and extracellular matrix in the cellular component category, and response to nutrient levels in the biological process category were most predominant. By KEGG pathway annotation, the different proteins between ACC and PA mainly participated in complement and coagulation cascades, amoebiasis, African trypanosomiasis and cholesterol metabolism. Eight proteins with mostly significant differences were verified by PRM, and five proteins with more than 10-fold increases in ACC compared with PA, including integrin ß, α-2-macroglobulin, epididymal secretory sperm binding protein Li 78p, RAB5C, and complement C5, were identified. CONCLUSION: The combined tools of label-free analysis and PRM are very effective and efficient, especially for samples such as tears. Some proteomic differences in tears between ACC and PA are identified and these protein candidates may be specific biomarkers for future exploration.

3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of PDK1 enhances the osimertinib sensitivity against osimertinib resistant xenograft and a patient derived xenograft (PDX) tumors. PDK1 knock-out dysregulates PI3K/Akt/mTOR signaling, promotes cell cycle arrest at the G1 phase. Yes-associated protein (YAP) and active-YAP are upregulated in resistant tumors, and PDK1 knock-out inhibits nuclear translocation of YAP. Higher expression of PDK1 and an association between PDK1 and YAP are found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP.

MiR-503 pleiotropically regulates epithelial-mesenchymal transition and targets PTK7 to control lung cancer metastasis.

OBJECTIVE: In lung cancer patients, most deaths are caused by the distant dissemination of cancer cells. Epithelial-mesenchymal transition (EMT) and collective cell migration are distinct and important mechanisms involved in cancer invasion and metastasis. Additionally, microRNA dysregulation contributes significantly to cancer progression. In this study, we aimed to explore the function of miR-503 in cancer metastasis. METHODS: Molecular manipulations (silencing or overexpression) were performed to investigate the biological functions of miR-503 including migration and invasion. Reorganization of cytoskeleton was assessed using immunofluorescence and the relationship between miR-503 and downstream protein tyrosine kinase 7 (PTK7) was assessed using quantitative real-time PCR, immunoblotting, and reporter assays. The tail vein metastatic animal experiments were performed. RESULTS: Herein, we demonstrated that the downregulation of miR-503 confers an invasive phenotype in lung cancer cells and provided in vivo evidence that miR-503 significantly inhibits metastasis. We found that miR-503 inversely regulates EMT, identified PTK7 as a novel miR-503 target, and showed the functional effects of miR-503 on cell migration and invasion were restored upon reconstitution of PTK7 expression. As PTK7 is a Wnt/planar cell polarity protein crucial for collective cell movement, these results implicated miR-503 in both EMT and collective migration. However, the expression of PTK7 did not influence EMT induction, suggesting that miR-503 regulates EMT through mechanisms other than PTK7 inhibition. Furthermore, we discovered that PTK7 mechanistically activates focal adhesion kinase (FAK) and paxillin, thereby controlling the reorganization of the cortical actin cytoskeleton. CONCLUSION: Collectively, miR-503 is capable of governing EMT and PTK7/FAK signaling independently to control the invasion and dissemination of lung cancer cells, indicating that miR-503 represents a pleiotropic regulator of cancer metastasis and hence a potential therapeutic target for lung cancer.

Geographical origin of Plasmodium vivax in the Hainan Island, China: insights from mitochondrial genome.

BACKGROUND: Hainan Province, China, has been an endemic region with high transmission of Plasmodium falciparum and Plasmodium vivax. Indigenous malaria caused by P. vivax was eliminated in Hainan in 2011, while imported vivax malaria remains. However, the geographical origin of P. vivax cases in Hainan remains unclear. METHODS: Indigenous and imported P. vivax isolates (n = 45) were collected from Hainan Province, and the 6 kb mitochondrial genome was obtained. Nucleotide (π) and haplotype (h) diversity were estimated using DnaSP. The numbers of synonymous nucleotide substitutions per synonymous site (dS) and nonsynonymous nucleotide substitutions per nonsynonymous site (dN) were calculated using the SNAP program. Arlequin software was used to estimate the genetic diversity index and assess population differentiation. Bayesian phylogenetic analysis of P. vivax was performed using MrBayes. A haplotype network was generated using the NETWORK program. RESULTS: In total, 983 complete mitochondrial genome sequences were collected, including 45 from this study and 938 publicly available from the NCBI. Thirty-three SNPs were identified, and 18 haplotypes were defined. The haplotype (0.834) and nucleotide (0.00061) diversity in the Hainan populations were higher than China's Anhui and Guizhou population, and the majority of pairwise FST values in Hainan exceeded 0.25, suggesting strong differentiation among most populations except in Southeast Asia. Most Hainan haplotypes were connected to South/East Asian and China's others haplotypes, but less connected with populations from China's Anhui and Guizhou provinces. Mitochondrial lineages of Hainan P. vivax belonged to clade 1 of four well-supported clades in a phylogenetic tree, most haplotypes of indigenous cases formed a subclade of clade 1, and the origin of seven imported cases (50%) could be inferred from the phylogenetic tree, but five imported cases (42.8%) could not be traced using the phylogenetic tree alone, necessitating epidemiological investigation. CONCLUSIONS: Indigenous cases in Hainan display high genetic (haplotype and nucleotide) diversity. Haplotype network analysis also revealed most haplotypes in Hainan were connected to the Southeast Asian populations and divergence to a cluster of China's other populations. According to the mtDNA phylogenetic tree, some haplotypes were shared between geographic populations, and some haplotypes have formed lineages. Multiple tests are needed to further explore the origin and expansion of P. vivax populations.

Different treatment efficacies and T790M acquisition of EGFR-TKIs on NSCLC patients with variable Del-19 subtypes of EGFR.

EGFR exon 19 deletion (Del-19) comprises multiple advanced NSCLC subtypes. EGFR-tyrosine kinase inhibitor (TKI) efficacy and T790M acquisition in various Del-19 subtypes is unknown. We prospectively collected tissue samples from patients harboring NSCLC with Del-19 between 2006 and 2020. We evaluated EGFR-TKI treatment effectiveness among the different Del-19 subtypes. We collected 1391 NSCLC samples from 892 patients with Del-19, and the most common subtype was del E746-A750 (67.5%). 741 patients had taken first- or second-generation EGFR-TKIs. There were no significant differences in response rates between patients with different Del-19 subtypes (P = .630). Patients with indel E746 had the longest median PFS (14.6 months), but those with non-LRE deletions had the shortest PFS (8.9 months; P = .002). For OS analysis, patients with indel E746 also had the longest OS (34.1 months), but those with non-LRE deletions had the shortest OS (21.1 months; P = .046). Patients with different Del-19 subtypes showed no significant differences in the T790M acquisition rates (P = .443). Among the 151 patients with acquired T790M who received third-generation EGFR-TKIs, the Del-19 subtype was not associated with different RR and PFS. In vitro cellular viability and activation of the EGFR pathway analysis were consistent with the clinical findings. In conclusion, compared with del E746-A750, indel E746 was associated with longer PFS and OS, but the non-LRE subtype was correlated with shorter survival prognosis. There were no significant differences in the acquired T790M rate and treatment effectiveness of subsequent third-generation EGFR-TKIs between various Del-19 subgroups.

Lacrimal sac lymphoma: a case series and literature review.

AIM: To study the clinical and pathological characteristics of the lacrimal sac lymphoma, which is rare but it is the major type of non-epithelial malignant tumor in the lacrimal sac region. METHODS: Sixty-four cases of malignant lacrimal sac tumors in our hospital from 1986 to 2020 were retrospectively reviewed. Eight cases of lacrimal sac lymphoma were carefully reviewed. RESULTS: There were five mucosal-associated lymphoid tissue (MALT) lymphomas, one diffused large B-cell lymphoma, one NK/T cell lymphoma, and one mantle cell lymphoma. All eight patients represented symptoms of epiphora with swelling in the lacrimal sac for a certain period of time and showed no signs of systemic involvement at the first time of clinical visits. They had received either chemotherapy or radiotherapy after surgery. Long-term follow-up (from 11 to 220mo) showed that, except one patient with MALT lymphoma died for unknown reasons at 104mo after surgery, the other 7 patients were all alive with no signs of local recurrence, neither in other organs. CONCLUSION: Non-epithelial malignant tumors of the lacrimal sac are rare and lymphoma is the major subtype.

An innovative three-layer strategy in response to a quartan malaria outbreak among forest goers in Hainan Island, China: a retrospective study.

BACKGROUND: An outbreak of Plasmodium malariae infection among forest goers in Sanya City of Hainan Island, China was reported in 2015. In response to this outbreak, an innovative three-layer strategy (TLS) targeted forest goers was adapted based on the 1-3-7 approach. MAIN TEXT: Key elements of TLS are: (i) The village with five malaria cases and adjacent villages were set as the first layer. All residents including forest goers were taken as the high-risk population (HRP). Active case detection (ACD) by blood smear microscopy and PCR was selected as the primary measure, and passive case detection (PCD) as complementary measure. One case was identified under TLS implementation. (ii) The township with cases (Gaofeng Town) and the nearby towns were chosen as the second layer. Only forest goers were screened by ACD, while PCD as a routine screening method. 7831 blood smears collected by ACD and PCD and tested with negative results. (iii) The city with cases (Sanya City) and others 12 counties/county-level cities were selected as the third layer. Malaria cases were monitored passively. A total of 77,555 blood slides were screened by PCD with zero positive sample. For each layer, the malaria vector mosquitoes were monitored using light traps, cattle-baited/human-bait traps. Anopheles minimus (dominant species), An. sinensis and An. dirus were captured. Vector control measures mainly include insecticide residual spraying and long-lasting insecticide nets. The capacity of clinicians, public health practitioners and laboratory technicians has been improved through training. During 2016‒2018, TLS and chemoprophylaxis were implemented in the same areas. In the first layer, all residents were monitored by ACD, and malaria chemoprophylaxis were distributed, 89.5% of forest goers were using chemoprophylaxis against malaria. The blood smears (3126 by ACD plus 1516 by PCD) were with zero positive results. Chemoprophylaxis and ACD were offered to forest goers once a year, and PCD in residents as a complementary measure in the second and third layer, 77.8% and 95.1% of forest goers received chemoprophylaxis. In each layer, vector surveillance and control of malaria and trainings for medical staff were still in place. CONCLUSIONS: TLS was effective in blocking the outbreak by P. malariae among forest goers in Hainan in malaria elimination stage. However, whether it could prevent the malaria resurgence in the post-elimination phase needs to be further assessed.

Prognostic value of early and late spontaneous conversion into a shockable rhythm for patients with out-of-hospital cardiac arrest.

BACKGROUND: The prognostic significance of conversion into a shockable rhythm in patients who experienced out-of-hospital cardiac arrest (OHCA) with an initially nonshockable rhythm is controversial, perhaps due to the timing of rhythm conversion not being considered previously. We aimed to compare the different prognoses of patients with OHCA and early and late conversion of their rhythm into a shockable rhythm. METHODS: This was a single-centre retrospective cohort study. We enrolled patients with OHCA who were sent to a medical centre in central Taiwan from 2016 to 2020. Patients <18 years old, those with cardiac arrest due to trauma or a circumstantial cause, and those for whom resuscitation was not attempted were excluded. Patients were divided into two groups in accordance with presentation with an initially shockable rhythm. Those with an initially nonshockable rhythm were divided into three subgroups: early-conversion, late-conversion, and nonconversion groups. The primary outcome was the neurological functional status upon discharge from hospital. RESULTS: A total of 1645 patients with OHCA were included: initially shockable rhythm group, 339; early conversion group, 68; late-conversion group, 166; and nonconversion group, 1072. After adjustment, multivariate logistic regression revealed that a favourable neurological outcome was more common in the early conversion group than the nonconversion group (odds ratio [OR] 2.4; 95% confidence interval [CI], 1.1-5.3; p = 0.035), whereas the late-conversion group did not significantly differ from the nonconversion group (OR 0.5; 95% CI, 0.1-1.5; p = 0.211). The proportions of sustained return of spontaneous circulation and survival to discharge were also higher in the early conversion group than the late-conversion group (OR 2.9 95% CI 1.6-5.5, p = 0.001 and OR 4.5, 1.8-11.0, p = 0.001, respectively). CONCLUSION: In patients who experience OHCA and have an initially nonshockable rhythm, early conversion into a shockable rhythm resulted in a better prognosis, whereas late conversion was not significantly different from nonconversion.

Significant Contribution of Interleukin-18 Genotypes to Lung Cancer Risk in Taiwanese.

BACKGROUND/AIM: The elevated expression of interleukin-18 (IL-18) among lung cancer patients raised our curiosity to examine the role of IL-18 genotypes in lung cancer. MATERIALS AND METHODS: IL-18 -656 (rs1946519), -607 (rs1946518), and -137 (rs187238) genotypes of 358 lung cancer cases and 716 controls were determined via the PCR-RFLP methodology. RESULTS: The distributions of genotypic and allelic frequencies of IL-18 -607, but not those of -656 or -137, were differentially distributed between cases and controls. IL-18 -607 AC and CC genotypes were both lower (45.8% and 16.2%) in lung cancer patients compared to controls (51.4% and 24.7%). In addition, IL-18 -607 AC and CC genotypes were of significantly lower percentages both among non-smokers and smokers. Otherwise, no differential distribution was found regarding IL-18 -656 or -137. CONCLUSION: IL-18 -607 C allele can serve as a protective predictor for lung cancer risk in Taiwanese.

Surveillance and response systems driving malaria elimination in the mountain areas of Hainan Province.

Hainan Province is in a tropical area of China and previously experienced serious P. falciparum and P. vivax malaria epidemics. After nearly 70 consecutive years of malaria prevention and control, malaria in Hainan has gradually been eliminated. To achieve the elimination of malaria, Hainan enacted six stages: investigative research and pilot prevention and control, large-scale antimalaria measures, adjustment of strategies for prevention and control, joint prevention and control measures, global funding of routine malaria control, and malaria elimination. Different strategies for malaria control were adopted at different stages. Malaria was most prevalent in the mountainous areas of central and southern Hainan, which contain a high-risk population (the forest goers) and two highly effective malaria vectors (An. dirus and An. minimus). Forest goers have been a high-risk population for malaria in Hainan since their identification in the 1990s. This paper summarizes malaria monitoring in forest goers and the response of forest goers to malaria control and elimination, distilling specific malaria control and elimination measures via case studies in Hainan Province. Two case studies in the malaria control stage demonstrated different measures for outbreaks and sporadic cases in forest goers. In view of the malaria outbreak in Sanya during the elimination stage, three-layered strategies (TLSs) were implemented to control outbreaks and improve control measures. Moreover, this paper also illustrates specific management measures to prevent malaria retransmission from sporadic imported malaria cases during the elimination phase. Hainan finally eliminated malaria in 2020. However, the risk of malaria retransmission is still high due to the prevalence of effective malaria vectors in Hainan, and forest goers are still a high-risk population for malaria retransmission.

Fucoidan with three functions extracted from Sargassum aquifolium integrated rice-husk synthesis dual-imaging mesoporous silica nanoparticle.

In this study, we used the nanoparticle delivery system to reduce the side effect of conventional cancer treatment- radiation therapy and chemotherapy. We used rice husk silicon source mesoporous silica nanoparticle doped in Eu3+ and Gd3+ as the carrier in the delivery system and to enable fluorescence and MRI dual-imaging functions for follow-up therapy. In addition, we choose a popular seaweed extract-fucoidan was extracted from the same brown algae-Sargassum aquifolium collected from Taiwan-Pingtung-Kenting-Chuanfan Rock. In this research, we used acid hydrolysis to prepared two different molecular weight fucoidan, the small molecular fucoidan (Fus) as drug, and the molecular weight approximately 1 kDa fucoidan (Ful) as the nanoparticle gatekeeper, and as targeting molecule for overexpressed P-selectin on the surface of the metastatic tumors. The results of the cell cytotoxicity experiment showed that HCT116 cancer cells have a survival rate of approximately 58.12% when treated with 200 µg/mL fucoidan. Dual-imaging rice husk mesoporous silica nanoparticles (rMSN-EuGd) were modified with 1 kDa fucoidan (Ful) as the gatekeeper and target, and the small molecule fucoidan (Fus) was loaded into nanoparticles (Ful-Fus@rMSN-EuGd) at a concentration of 200 µg/mL. The HCT116 cancer cells had a survival rate of approximately 55.56%. The cell cytotoxicity experiment results show that Ful-Fus@rMSN-EuGd can improve the anticancer effect of fucoidan, and the nanoparticle drug delivery system using fucoidan as a drug, target, and gatekeeper was successfully synthesized.