Adenosine Encapsulation and Characterization through Layer-by-Layer Assembly of Hydroxypropyl-ß-Cyclodextrin and Whey Protein Isolate as Wall Materials.

Adenosine, as a water-soluble active substance, has various pharmacological effects. This study proposes a layer-by-layer assembly method of composite wall materials, using hydroxypropyl-ß-cyclodextrin as the inner wall and whey protein isolate as the outer wall, to encapsulate adenosine within the core material, aiming to enhance adenosine microcapsules' stability through intermolecular interactions. By combining isothermal titration calorimetry with molecular modeling analysis, it was determined that the core material and the inner wall and the inner wall and the outer wall interact through intermolecular forces. Adenosine and hydroxypropyl-ß-cyclodextrin form an optimal 1:1 complex through hydrophobic interactions, while hydroxypropyl-ß-cyclodextrin and whey protein isolate interact through hydrogen bonds. The embedding rate of AD/Hp-ß-CD/WPI microcapsules was 36.80%, and the 24 h retention rate under the release behavior test was 76.09%. The method of preparing adenosine microcapsules using composite wall materials is environmentally friendly and shows broad application prospects in storage and delivery systems with sustained release properties.

ISG15 Promotes Progression and Gemcitabine Resistance of Pancreatic Cancer Cells Through ATG7.

Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both in vitro and in vivo. ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.

Clinical Features and Predictive Nomogram of Acute Kidney Injury in Aging Population Infected with SARS-CoV-2 Omicron Variant.

Background: Since little is known about the acute kidney injury (AKI) in aging population infected with SARS-CoV-2 Omicron variant, we investigated the incidence, clinical features, risk factors and mid-term outcomes of AKI in hospitalized geriatric patients with and without COVID-19 and established a prediction model for mortality. Methods: A real-time data from the Shanghai Ninth People's Hospital information system of inpatients with COVID-19 from 1 April 2022 to 30 June 2022 were extracted. Clinical spectrum, laboratory results, and clinical prognosis were included for the risk analyses. Moreover, Cox and Lasso regression analyses were applied to predict the 90-day death and a nomogram was established. Results: A total of 1607 SARS-CoV-2 infected patients were enrolled; hypertension was the most common comorbidity, followed by chronic cardiovascular disease, diabetes mellitus, and lung disease. Most of the participants were non-vaccinated and the mean age of patients was 82.6 years old (range, 60-103 years). The AKI incidence was higher in relatively older patients (16.29% vs 3.63% in patients older than 80 years and 60 to 80 years, respectively). Linear regression models identified some variables associated with the incidence of AKI, such as older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment. In this cohort, 11 patients died in-hospital and 21 patients died at 90-day follow-up. The predictive nomogram of 90-day death achieved a good C-index of 0.823 by using 5 predictor variables: ICU admission, D-dimer, peak of serum creatinine, rate of serum creatinine decline and white blood cell count (WBC). Conclusion: Older age, clinical spectrum, D-dimer level, number of comorbidities, baseline eGFR, and antibiotic or corticosteroid treatment are clinical risk factors for the incidence of AKI in geriatric COVID-19 patients. The prediction nomogram achieved an excellent performance at the prediction of 90-day mortality.

Selective activation of STAT3 and STAT5 dictates the fate of myeloid progenitor cells.

The molecular programs that govern the directed differentiation of myeloid progenitor cells are still poorly defined. Using a previously established immortalized, phenotypically normal myeloid progenitor cell model mEB8-ER, we unveil a new mechanism mediated by STAT5 and STAT3 at a bifurcation point of myeloid progenitor cell-fate specification. We find that myeloid progenitor cells can spontaneously differentiate into neutrophils with a basal level of STAT3 phosphorylation, which is enhanced by G-CSF treatment or STAT3 over-expression, leading to elevated neutrophil differentiation. Reduced STAT3 phosphorylation caused by GM-CSF treatment, STAT3 specific inhibitor, or STAT3 depletion leads to attenuated myeloid differentiation into neutrophils, while elevating differentiation into monocytes/macrophages. In contrast, STAT5 appears to have an antagonistic function to STAT3. When activated by GM-CSF, STAT5 promotes myeloid differentiation into monocytes/macrophages but inhibits neutrophil differentiation. At the mechanistic level, GM-CSF activates STAT5 to up-regulate SOCS3, which attenuates STAT3 phosphorylation and consequently neutrophil differentiation, while enhancing monocyte/macrophage differentiation. Furthermore, inhibition of STAT5 and STAT3 in primary myeloid progenitors recapitulates the results from the mEB8-ER model. Together, our findings provide new mechanistic insights into myeloid differentiation and may prove useful for the diagnosis and treatment of diseases related to abnormal myeloid differentiation.

Preparation of enzymolysis porous corn starch composite microcapsules embedding organic sunscreen agents and its UV protection performance and stability.

In this paper, a natural composite wall material sunscreen microcapsule was prepared, which significantly improved the SPF value and photostability of the embedded sunscreen agents. Using modified porous corn starch and whey protein as wall materials, the sunscreen agents 2-[4-(diethylamino)-2-hydroxybenzoyl] benzoic acid hexyl ester and ethylhexyl methoxycinnamate were embedded by adsorption, emulsion, encapsulation and solidification. The embedding rate of the obtained sunscreen microcapsules was 32.71 % and the average size was 7.98 µm; the enzymatic hydrolyzed starch formed a porous structure, its X-ray diffraction pattern did not change significantly, and the specific volume and oil absorption rate increased by 39.89 % and 68.32 %, respectively, compared with those before enzymatic hydrolyzed; The porous surface of the starch after embedding the sunscreen was covered and sealed with whey protein. 120 h sunscreen penetration rate was lower than 12.48 %; Compared with the lotion containing the same amount of sunscreen but not encapsulated, the SPF value of the lotion containing sunscreen microcapsules increased by 62.24 %, and the photostability of sunscreen microcapsules increased by 66.28 % within 8 h under the irradiation intensity of 25 w/m2. The wall material and the preparation method are natural and environmentally friendly, and have a good application prospect in low-leakage drug delivery system.

The prognostic value and biological functions of HFM1 in breast cancer.

Aim: HFM1 has been reported to be associated with meiosis and ovarian insufficiency, but its role in tumors remains unknown. This study aims to explore the functions and potential mechanism of HFM1 in breast cancer. Methods: Several databases, protein-protein interactions, gene ontology and the Kyoto Encyclopedia of Genes and Genomes were used for bioinformatic analysis. Tissue microarrays and cell viability assays were used to detect the expression of HFM1 and tamoxifen resistance, respectively. Results: HFM1 was downregulated in breast cancer with poor prognosis and may modulate DNA damage repair pathways and immune infiltration. Moreover, HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Conclusion: We presented a first study on biological functions and potential mechanisms of HFM1 in cancers.

The role and function of the protein HFM1 in tumors remains unknown. We explored the functions and potential mechanism of HFM1 in breast cancer through several known databases, clinical samples and cell experiments. We found that HFM1 was downregulated in breast cancer with a poor prognosis. HFM1 may mediate ovarian steroidogenesis and participate in tamoxifen resistance of estrogen receptor-positive breast cancer cells. Here we first put forward the relationship between HFM1 and the prognosis of breast cancer, and provided relevant clues for mechanism exploration.

Upregulation of KLHL17 promotes the proliferation and migration of non-small cell lung cancer by activating the Ras/MAPK signaling pathway.

Analysis of the Gene Expression Profiling Interactive Analysis (GEPIA) database revealed that Kelch-like 17 (KLHL17) is overexpressed in non-small cell lung cancer (NSCLC) including adenocarcinoma (ADC) and squamous cell carcinoma (SCC). We therefore explored the role of KLHL17 in the development and progression of NSCLC. Immunohistochemistry and western blotting showed that KLHL17 expression was significantly higher in the tumor tissues from 173 patients with NSCLC, compared with the corresponding non-neoplastic tissue. In addition, upregulated KLHL17 expression was positively correlated with tumor size, lymph node metastasis and tumor node metastasis (TNM) stage, and affected the overall survival (OS) of patients with NSCLC. Consistent with clinical samples, in vitro studies demonstrated that KLHL17 expression was higher in various cell lines of NSCLC (A549, H1299, H460 and SK cells) as compared to normal human bronchial epithelial cells (HBE cells). Overexpression of KLHL17 in the cell lines of NSCLC with KLHL17-Flag plasmid promoted the proliferation and migration of tumor cells, which was associated with elevated activation of Rat sarcoma/Mitogen-activated protein kinases (Ras/MAPK) signaling and increased expression of cyclin D1, cyclin D-dependent kinases 4 (CDK4), matrix metalloproteinase 2 (MMP2) and Ras homolog gene family member A (RhoA). In contrast, knockdown of KLHL17 in the cell lines of NSCLC using KLHL17 small interfering RNA suppressed the proliferation and migration of tumor cells, in association with reduced activation of Ras/MAPK signaling and decreased expression of cyclin D1, CDK4, MMP2 and RhoA. Moreover, treatment of tumor cells with Ras inhibitor salirasib prevented KLHL17-induced Ras/MAPK activity as well as tumor proliferation and migration. These results suggest that upregulated KLHL17 in NSCLC promotes the proliferation and migration of tumor by activating Ras/MAPK signaling pathway. Therefore, KLHL17 may be a novel therapeutic target for the treatment of NSCLC.

A comprehensive bioinformatic analysis of RanBP9 expression and its relation to prognosis in human breast cancer.

Aim: To explore the role of RanBP9 in breast cancer. Materials & methods: Oncomine, TIMER, GEPIA, UALCAN, c-BioPortal databases and tissue microarray analysis were used in this study. Results: The expression level of RanBP9 is elevated in breast cancer tissues, which is associated with poor prognosis in breast cancer patients. RanBP9 exhibits genetic alterations and a decreased methylation level in cancer tissues. RanBP9 may also regulate cell cycle progression and is linked to tumor purity and the infiltrating levels of immune cells. Conclusions:RanBP9 may correlate with prognosis and immune infiltration in breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.

Lay abstract RanBP9 has diverse function in various tumor types. However, the role of RanBP9 in breast cancer remains to be explored. In this study, we investigated the gene expression of RanBP9 using databases and clinical samples. We found the expression level of RanBP9 is raised in breast cancer tissues and is associated with poor prognosis for breast cancer patients. RanBP9 may be involved in the regulation of the cell cycle and related to tumor immunity. Overall, we found that RanBP9 may correlate with prognosis and immune infiltration of breast cancer, laying the foundation for future studies on the potential role of RanBP9 in breast cancer.

Transformation of advanced lung adenocarcinoma to acquired T790M resistance mutation adenosquamous carcinoma following tyrosine kinase inhibitor: a case report.

BACKGROUND: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are recommended for patients with non-small cell lung cancer with EGFR mutations. However, acquired resistance to EGFR-TKIs seems inevitable and the mechanism of drug resistance has not been fully defined. There is no effective treatment for patients with advanced lung adenocarcinoma who are resistant to TKIs owing to pathologic type conversion. CASE PRESENTATION: We report a patient who was initially diagnosed with lung adenocarcinoma. At first, she was sensitive to the first-generation TKI icotinib. After 17 months of treatment, the patient acquired resistance to icotinib. Moreover, after tumor resection, immunohistochemical analysis showed pathologic change from adenocarcinoma to adenosquamous carcinoma, and next-generation sequencing technology discovered EGFR exon19 p.745-750 del, exon20 p.T790M, and KMT2C exon 18 p.R973G mutations. After video-assisted tumor resection, the patient is receiving osimertinib (AZD 9291). Current overall survival is 60 months. CONCLUSIONS: Surgical intervention may prolong survival time in patients with acquired TKI resistance, especially when there is no evidence of metastasis.

Foxp3 TSDR Hypermethylation Is Correlated with Decreased Tregs in Patients with Unexplained Recurrent Spontaneous Abortion.

A decline of T regulatory cell (Treg) number and function is associated with unexplained recurrent spontaneous abortion (URSA). However, the mechanism of downregulation of Tregs in URSA patients is still unknown. This study aimed to investigate the changes of Tregs in URSA patients and the epigenetic regulation for these changes. Venous blood samples were collected from 20 patients with URSA and 20 healthy control subjects. Treg number and inhibitory capacity, and Foxp3 mRNA expression and Foxp3 TSDR methylation were compared between the 2 groups. Correlations between Treg frequency and inhibitory function and TSDR methylation status were examined by Spearman's correlation. The proportion of Tregs within the population of CD4+ T cells and the expression of Foxp3 mRNA was significantly lower in URSA patients than in healthy control subjects. Tregs from URSA patients and healthy controls both significantly inhibited the cytotoxic activity of natural killer (NK) cells toward K562 targets; however, the inhibitory ability of Tregs from URSA patients was significantly lower than that from healthy controls. The methylation level of the Treg-specific demethylated region (TSDR) in the Foxp3 gene was significantly greater in URSA patients than in the controls, and the level of methylation was inversely correlated with the proportion of Tregs and Foxp3 mRNA expression in the peripheral blood. However, the methylation level was not correlated with the inhibitory function of Tregs. A decrease of Treg number and function may be related to the pathogenesis of URSA, and Foxp3 hypermethylation may be associated with the decreased Treg number.

Silencing of long non-coding RNA MEG3 alleviates lipopolysaccharide-induced acute lung injury by acting as a molecular sponge of microRNA-7b to modulate NLRP3.

We aimed to elucidate the roles of the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3)/microRNA-7b (miR-7b)/NLR pyrin domain containing 3 (NLRP3) axis in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Mouse alveolar macrophage NR8383 and mice were administrated with LPS to establish ALI models in vitro and in vivo. NLRP3 was silenced while miR-7b was overexpressed in LPS-induced NR8383 cell model of ALI. The interleukin-18 (IL-18) and IL-1ß, as well as caspase-1, tumor necrosis factor-α (TNF-α) and IL-6 protein levels were assayed. To further investigate the underlying mechanisms of NLRP3 in ALI, lncRNA MEG3 was silenced and miR-7b was overexpressed in LPS-induced NR8383 cell model of ALI, after which in vivo experiments were performed for further verification. NLRP3 was highly expressed in LPS-induced NR8383 cell model of ALI. Silencing NLRP3 or overexpressing miR-7b inhibited IL-18 and IL-1ß, as well as caspase-1, TNF-α and IL-6. LncRNA MEG3 could sponge miR-7b, and lncRNA MEG3 silencing or miR-7b overexpression downregulates NLRP3 expression, thus reducing IL-18 and IL-1ß, as well as caspase-1, TNF-α and IL-6 levels. The in vivo experiments further confirmed the aforementioned findings. Silencing lncRNA MEG3 augments miR-7b binding to NLRP3 and downregulates NLRP3 expression, which ultimately improves LPS-induced ALI.

An integrative investigation on significant mutations and their down-stream pathways in lung squamous cell carcinoma reveals CUL3/KEAP1/NRF2 relevant subtypes.

BACKGROUND: Molecular mechanism of lung squamous cell carcinoma (LUSC) remains poorly understood, hampering effective targeted therapies or precision diagnosis about LUSC. We devised an integrative framework to investigate on the molecular patterns of LUSC by systematically mining the genomic, transcriptional and clinical information. METHODS: We utilized the genomics and transcriptomics data for the LUSC cohorts in The Cancer Genome Atlas.. Both kinds of omics data for 33 types of cancers were downloaded from The NCI's Genomic Data Commons (GDC) (https://gdc.cancer.gov/about-data/publications/pancanatlas). The genomics data were processed in mutation annotation format (maf), and the transcriptomics data were determined by RNA-seq method. Mutation significance was estimated by MutSigCV. Prognosis analysis was based on the cox proportional hazards regression (Coxph) model. RESULTS: Significant somatic mutated genes (SMGs) like NFE2L2, RASA1 and COL11A1 and their potential down-stream pathways were recognized. Furthermore, two LUSC-specific and prognosis-meaningful subtypes were identified. Interestingly, the good prognosis subtype was enriched with mutations in CUL3/KEAP1/NRF2 pathway and with markedly suppressed expressions of multiple down-stream pathways like epithelial mesenchymal transition. The subtypes were verified by the other two cohorts. Additionally, primarily regulated down-stream elements of different SMGs were also estimated. NFE2L2, KEAP1 and RASA1 mutations showed remarkable effects on the subtype-determinant gene expressions, especially for the inflammatory relevant genes. CONCLUSIONS: This study supplies valuable references on potential down-stream processes of SMGs and an alternative way to classify LUSC.

Long-term safety of icotinib in patients with non-small cell lung cancer: a retrospective, real-world study.

BACKGROUND: Lung cancer is a global health problem with a high mortality, and the development of target therapy has led to a revolution in the treatment of lung cancer in recent years. Favorable efficacy and safety of icotinib have been demonstrated in patients with non-small cell lung cancer (NSCLC). Currently, minimal data are available to describe the long-term safety of icotinib in NSCLC patients. METHODS: We reviewed the safety data from 1,321 advanced NSCLC patients who were treated with icotinib. The primary endpoint was the long-term safety, defined as any adverse drug reactions (ADRs) occurred after 6 months of icotinib administration. RESULTS: Fewer ADRs were noticed over 6 month administration of icotinib than within 6 months in overall population (24.3% vs. 65.4%), and elderly patients (23.6% vs. 66.9%). The majority of ADRs were grade 1-2 in severity over 6 month exposure of icotinib in overall population as well as elderly patients. In overall population, the most common ADRs of icotinib during long-term use were rash (16.4%) and diarrhea (5.3%), while the incidences were 31.8% and 13.2% in the induction period, respectively. In elderly population, the most common ADRs of icotinib during long-term use were rash (15.7%) and diarrhea (4.7%), while the incidences were 27.8% and 14.9% in the induction period, respectively, and more inching was observed in the induction period as compared with long term use (6.3% vs. 0.3%). CONCLUSIONS: There was an evidence of decreased frequency of icotinib-induced ADRs over time, and icotinib was well-tolerated in elderly NSCLC patients.

[Application of calixarene stationary phases to liquid chromatography].

Calixarenes are cyclic oligomers composed of phenol units linked by methylene bridges. Because of their unique host-guest recognition ability, calixarenes are considered to be the main representatives of the third generation of supramolecular chemistry after crown ethers and cyclodextrins. Calixarenes are widely used in ion channel as well as in organic catalytic reactions, transmembrane transport, purification, and chromatographic separation. A variety of versatile calixarene derivatives with different recognition ability and special selectivity were prepared by modifying different types of compounds due to calixarenes are easy to derivatize. These derivatives were successfully applied to different chromatographic modes to achieve the separation and analysis of complex samples. This review summarizes the recent advances in stationary phases based on calixarenes and their derivatives for liquid chromatography The prospects of calixarenes in chromatographic separation science are also presented.

[Application and exploration of micro-class combined with flipped classroom in cardiopulmonary resuscitation teaching for dental students].

PURPOSE: To explore the application of micro-class combined with flipped classroom in cardiopulmonary resuscitation teaching for dental students. METHODS: The experimental group included 46 students from grade 2014 in college of stomatology, Shanghai Jiao Tong University. The control group included 45 students from grade 2013. Students in the control group were taught in traditional method, while those in the experimental group were taught in micro-class combined with flipped classroom teaching. After the course, we compared the outcome of didactic test and skill evaluation about CPR. A questionnaire survey was conducted in the experimental group. SPSS16.0 software was employed for statistical analysis. RESULTS: The results of didactic test and skill evaluation in the experimental group was significantly better than that in the control group(P<0.05). The results of questionnaire showed that application of micro-class combined with flipped classroom was appreciated by over 80% students. CONCLUSIONS: The implementation of micro-class combined with flipped classroom can achieve a better teaching effect in cardiopulmonary resuscitation teaching for dental students.

MiR-361 targets Yes-associated protein (YAP) mRNA to suppress cell proliferation in lung cancer.

Yes-associated protein (YAP) contributes to the development of multiple tumors, but the post-transcription modulation of YAP remains unexplored. Here, we present a new regulatory microRNA of YAP, miR-361, which directly targets YAP to inhibit cell proliferation in lung cancer. We used bioinformatics to predict that miR-361 could target 3'-untranslated region (3'UTR) of YAP mRNA. Luciferase reporter gene assays demonstrated that miR-361 could decrease the luciferase activities of 3'UTR vector of YAP. Furthermore, YAP expression was obviously abated by miR-361 using RT-PCR and immunoblotting in lung cancer A549 cells. In terms of function, MTT and colony formation analysis showed that ectopic miR-361 expression significantly suppressed cell proliferation in lung cancer. Notably, overexpressed YAP accelerated miR-361-bated proliferation of lung cancer cells. MiR-361 inhibitor promoted cell proliferation in lung cancer, but YAP RNA interference reversed miR-361 inhibitor-driven cell proliferation. Interestingly, miR-361 was capable of affecting the cell cycle in lung cancer progression. Finally, the negative correlation of miR-361 with YAP was found in clinical human lung cancer tissues. In conclusion, miR-361 targets 3'UTR of YAP mRNA to depress the proliferation of lung cancer cells.

The feasibility and advantage of uniportal video-assisted thoracoscopic surgery (VATS) in pulmonary lobectomy.

BACKGROUND: Ongoing improvements in technique and instruments for video-assisted thoracoscopic surgery (VATS) have made minimally-invasive uniportal VATS lobectomy a reality. However, the outcomes of the procedure are still under investigation, and at present, uniportal VATS lobectomy is performed infrequently at most hospitals. We have therefore reviewed our outcomes with this procedure in an attempt to validate its safety, efficacy, and feasibility. METHODS: We retrospectively analyzed and compared perioperative data for patients who underwent uniportal, two-port, and traditional three-port VATS lobectomy between January 2015 and December 2015 at our hospital. RESULTS: Among 257 patients who had successful VATS lobectomy during the study period, 73 underwent uniportal VATS, 86 underwent two-port VATS, and 98 underwent traditional three-port VATS. There were no surgical or 30-day postoperative mortalities, and no significant differences in operative times, blood loss, number of lymph nodes retrieved and nodal stations explored, drainage times, length of hospital stay, or postoperative complications among the three groups. The visual analogue scale (VAS) pain scores were significantly lower in the uniportal VATS group after surgery (P < 0.05). CONCLUSIONS: Uniportal VATS lobectomy is a safe and feasible surgical procedure that is associated with decreased surgical trauma and less postoperative pain compared to traditional VATS. Further long term follow-up analyses in large numbers of patients are ongoing.

The stability and controlled release of I-ascorbic acid encapsulated in poly (ethyl-2-cyanoacrylate) nanocapsules prepared by interfacial polymerization of water-in-oil microemulsions.

The L-ascorbic acid (AA) was encapsulated into biodegradable and biocompatible poly(ethyl-2-cyanoacrylate) (PECA) nanocapsules by interfacial polymerization of water-in-oil (W/O) microemulsions. The influences of surfactant concentration, pH value of the dispersed aqueous phase, and W/O ratio on nanocapsule size were discussed. The stability and in vitro release of encapsulated AA were also investigated. The results show that nanocapsules could be obtained under the conditions with low pH value, high fraction of aqueous phase, and appropriate surfactant concentration. The encapsulated AA was protected by nanocapsules from oxidation and presented superior storage stability in aqueous medium than pure AA. Releasing AA from the inner core of nanocapsules could be controlled by adjusting the enzyme hydrolysis extent of the PECA wall.

Alpinetin inhibits lung cancer progression and elevates sensitization drug-resistant lung cancer cells to cis-diammined dichloridoplatium.

OBJECTIVE: Alpinetin is a novel flavonoid that has demonstrated potent antitumor activity in previous studies. However, the efficacy and mechanism of alpinetin in treating lung cancer have not been determined. METHODS: We evaluated the impact of different doses and durations of alpinetin treatment on the cell proliferation, the apoptosis of lung cancer cells, as well as the drug-resistant lung cancer cells. RESULTS: This study showed that the alpinetin inhibited the cell proliferation, enhanced the apoptosis, and inhibited the PI3K/Akt signaling in lung cancer cells. Moreover, alpinetin significantly increased the sensitivity of drug-resistant lung cancer cells to the chemotherapeutic effect of cis-diammined dichloridoplatium. Taken together, this study demonstrated that alpinetin significantly suppressed the development of human lung cancer possibly by influencing mitochondria and the PI3K/Akt signaling pathway and sensitized drug-resistant lung cancer cells. CONCLUSION: Alpinetin may be used as a potential compound for combinatorial therapy or as a complement to other chemotherapeutic agents when multiple lines of treatments have failed to reduce lung cancer.

Airway Reconstruction with Autologous Pulmonary Tissue Flap and an Elastic Metallic Stent.

To pursue a suitable central airway replacement, we conducted central airway reconstruction using autologous pulmonary tissue flaps lined with alloy stents in five patients after extensive tracheal resection. Preoperative and postoperative arterial blood gas analysis and pulmonary function tests were used to evaluate efficacy of this technique. All patients demonstrated improved arterial blood gas values and pulmonary function. Follow-up bronchoscopy and chest computed tomography scan showed that each reconstructed trachea lacked swing or structural damage, and that each transplanted pulmonary tissue flap had ample blood circulation. After as long as 84 months follow-up, four patients reported no complications, although one patient died from severe hemoptysis 14 months after the surgery. The application of central airway reconstruction using an autologous pulmonary tissue flap lined with an elastic metallic stent provides a promising alternative for patients with thoracic tracheal defects.