The ALK rearrangements are independently associated with younger age and the EGFR wild type. The EGFR mutations and the ALK rearrangements are rarely coexistent. The ALK rearrangements and the KRAS mutations are mutually exclusive.

The aim of this study was to investigate the role of luteolin in the mechanism of ultraviolet radiation B (UVB)-induced photoaging. An in vivo photoaging model was established using UVB irradiation of bare skin on the back of rats, and an in vitro photoaging model was established using UVB irradiation of human dermal fibroblasts (HDF). Skin damage was observed using hematoxylin-eosin (HE) and Masson staining, skin and cellular reactive oxygen species (ROS) levels were detected by DHE and DCF fluorescent probes, mitochondrial membrane potential was detected by JC-1 staining, and protein expressions were detected by immunofluorescence and Western Blot. Results from animal experiments showed that luteolin reduced UVB-induced erythema and wrinkle formation. Results from cellular assays showed that luteolin inhibited UVB-induced decrease in cell viability. In addition, in vitro and in vivo experiments showed that luteolin reduced oxidative stress levels, decreased activation of matrix metalloproteinases (MMPs) and increased collagen expression. Continued cellular experiments using 3-TYP, an inhibitor of Sirtuin 3 (SIRT3), revealed a loss of cellular protection by luteolin and a decrease in collagen, suggesting that luteolin acts by targeting and promoting SIRT3. luteolin is involved in the protection of skin cells against UVB radiation-induced ageing via the SIRT3/ROS/mitogen-activated protein kinases (MAPK) axis and it may be a promising therapeutic agent for the prevention of UVB photoaging.

Abstract. The present study aimed to investigate the association between epidermal growth factor receptor (EGFR)/Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations, anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangements and the morphological characteristics of lung adenocarcinoma (LAC), according to the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) classification in a large group of patients with primary LAC. A total of 200 patients with invasive LAC who had undergone complete resections at the Beijing Chest Hospital (Beijing, China) were randomly selected. The morphology of the samples was reassessed in 5% increments by two pathologists, according to the IASLC/ATS/ERS scheme. EGFR and KRAS mutations were tested by direct DNA sequencing. ALK rearrangements were screened by immunohistochemistry on a Benchmark XT stainer. The data revealed that EGFR and KRAS mutations, and ALK rearrangements were identified in 46.0% (92/200), 9.0% (18/200) and 11.5% (23/200) of the patients, respectively. The EGFR/KRAS mutations and ALK rearrangements were mostly exclusive. However, 1 patient exhibited the coexistence of the EGFR (at exon 20) and KRAS (codon 12) mutations, and another patient exhibited the coexistence of the EGFR mutation (at exon 21) and the ALK gene fusion. EGFR mutations were indicated to be closely associated with the acinar predominant (43/77; 55.8%; P=0.030) and papillary predominant (26/49; 53.1%; P=0.006) subtypes. KRAS mutations were more commonly associated with the solid predominant subtype (9/52; 17.3%; P=0.023) and invasive mucinous LAC (5/10; 50.0%; P=0.004), and less commonly associated with the acinar predominant subtype (1/77; 1.3%; P=0.002). ALK rearrangements more commonly occurred in the solid predominant subtype compared with other subtypes (13/52; 25%; P=0.002), and less commonly occurred in the papillary predominant subtype (1/49; 2.0%; P=0.004). Tumors harboring ALK rearrangements were characterized by signet-ring cell (7/9; 77.8%; P<0.0001) and cribriform (7/12; 58.3%; P<0.0001) patterns. The association between the mutation status and histological subtype in LAC was distinct. The predominant subtype according to the IASLC/ATS/ERS classification provided important information for gene mutations and integrated clinical findings to improve the treatment of LAC patients.

Abstract. Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related deaths. Aberrance of the two oncogenes MET and SOX2 are frequently encountered in NSCLC. Exons 18 through 21 of the EGFR gene were screened and MET and SOX2 immunostaining was conducted to analyze the immunohistological staining of MET and SOX2 and the EGFR mutation status. One hundred and fifty tissue samples were examined including 57 squamous cell carcinomas (SCCs), 80 adenocarcinomas (ADCs), 9 adenosquamous carcinomas (ADSCs) and 4 large cell carcinomas (LCCs). The 32 NSCLCs harboring an EGFR mutation included 28 ADCs, 3 SCCs and 1 ADSC. A higher level of SOX2 expression appeared in NSCLCs without the EGFR mutation compared to those with EGFR mutation (χ 2 =9.02, P=0.0027). Of the 28 ADCs, 24 (85.7%) with an EGFR mutation showed low level of SOX2 expression. ADCs with deletion in exon 19 overexpressed MET and showed low levels of SOX2. SOX2 expression was inversely correlated to the expression of MET in NSCLC and mainly present in non-mutated NSCLC (r=-0.42, P<0.0001). There was a tendency for SOX2 to be expressed in SCCs and particularly in the part of SCC among ADSCs, whereas MET was mainly expressed in the part of ADC among ADSCs and ADCs. High level of MET and SOX2 expression were respectively demonstrated in ADCs and SCCs; MET activation was accompanied with exon 19 deletion in ADCs. EGFR and MET coordinate to drive tumorigenesis. Detection of the activation of MET and EGFR may be used for targeted drug therapy.

Selenium nanoparticles (SeNPs) can be produced by biogenic, physical, and chemical processes. The physical and chemical processes have hazardous effects. However, biogenic synthesis (by microorganisms) is an eco-friendly and economical technique that is non-toxic to human and animal health. The mechanism for biogenic SeNPs from microorganisms is still not well understood. Over the past two decades, extensive research has been conducted on the nutritional and therapeutic applications of biogenic SeNPs. The research revealed that biogenic SeNPs are considered novel competitors in the pharmaceutical and food industries, as they have been shown to be virtually non-toxic when used in medical practice and as dietary supplements and release only trace amounts of Se ions when ingested. Various pathogenic and probiotic/nonpathogenic bacteria are used for the biogenic synthesis of SeNPs. However, in the case of biosynthesis by pathogenic bacteria, extraction and purification techniques are required for further useful applications of these biogenic SeNPs. This review focuses on the applications of SeNPs (derived from probiotic/nonpathogenic organisms) as promising anticancer agents. This review describes that SeNPs derived from probiotic/nonpathogenic organisms are considered safe for human consumption. These biogenic SeNPs reduce oxidative stress in the human body and have also been shown to be effective against breast, prostate, lung, liver, and colon cancers. This review provides helpful information on the safe use of biogenic SeNPs and their economic importance for dietary and therapeutic purposes, especially as anticancer agents.

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Objective. To investigate the effects and corresponding mechanisms of total flavonoids (TFL) from Lycium barbarum leaves on photoaged human dermal fibroblasts (HDFs). Methods. Crude TFL was extracted with 70% ethanol, and a Rutin standard curve was drawn using the sodium nitrite-aluminum nitrate-sodium hydroxide colorimetry method to calculate its yield and mass concentration. After that, the photoaging HDFs model was established by UVA combined with 8-MOP. CCK-8 was performed to assess the influence of TFL on the proliferation of HDFs and photoaging HDFs. β-galactosidase (SA-β-gal) staining and activity assays were performed to evaluate the activity of SA-β-gal and the rate of SA-β-gal-positive cells in HDFs cells. The level of skin ECM proteins and oxidative stress-related substances in HDFs cells of each group was determined by ELISA and biochemical detection, respectively. Apoptosis of HDFs in each group was assessed by flow cytometry. The expressions of MAPK signaling pathway-related proteins in HDFs were detected by western blot. Results. The yield rate of TFL extracted by 70% ethanol was 41.9%, and its purity rate was 34.6%. TFL at 25, 50, and 100 μg/mL was able to greatly promote the proliferation of HDFs. A photoaged HDFs model was successfully constructed by combining UVA irradiation at 9 J/cm2 and 8-MOP at 50 mg/L. TFL treatment could significantly inhibit apoptosis, SA-β-gal-positive cell staining rate, SA-β-gal activity, lactate dehydrogenase (LDH) leakage, and malondialdehyde (MDA) content in photoaged HDFs. Further, TFL increased the proliferative activity, superoxide dismutase (SOD) activity, catalase (CAT) activity, type I collagen (Col I), hydroxyproline (HYP), and hyaluronic acid (HA) level of photoaged HDFs in a dose-dependent manner. Additional experiments suggested that TFL played a protective role by downregulating MAPK signaling pathway activity in photoaged HDFs cells. Conclusion. TFL could inhibit oxidative stress and apoptosis, promote cell proliferation and the level of ECM-related component proteins, and participate in antiphotoaging in a concentration-dependent manner. The protective role of TFL in photoaged HDFs might be related to its inhibition of MAPK signaling pathways.

Objectives The MeltPro MTB assays for detection of resistance to antituberculosis (TB) drugs perform well in genotypic drug susceptibility testing (DST) of clinical samples, but their effectiveness with formalin-fixed, paraffin-embedded (FFPE) tissues is unknown. Methods FFPE tissues were obtained from 334 patients with TB. Susceptibility to rifampicin (RIF), isoniazid (INH), and fluoroquinolones was examined using the MeltPro MTB assays, with Xpert MTB/RIF (Xpert) and/or phenotypic DST (pDST) results as references. Samples with discordant results were analyzed by multiplex polymerase chain reaction–targeted amplicon sequencing (MTA-seq). Results With pDST as the reference, the MeltPro MTB assays sensitivity for RIF, INH, levofloxacin (LVX), and moxifloxacin (MXF) was 95.00%, 96.00%, 100%, and 100%, respectively, and the specificity was 95.15%, 95.92%, 94.69%, and 89.92%, respectively. Concordance was 99.08% between the MeltPro MTB and Xpert (κ = 0.956) for RIF and 95.12% (κ = 0.834), 95.93% (κ = 0.880), 95.12% (κ = 0.744), and 90.24% (κ = 0.367) between the MeltPro MTB and pDST for RIF, INH, LVX, and MXF, respectively. MTA-seq confirmed the discordancy between the MeltPro MTB and pDST for 26 (89.66%) of 29 samples. Conclusions The MeltPro MTB assays rapidly and efficiently predict Mycobacterium tuberculosis resistance to the main first- and second-line anti-TB drugs in FFPE tissues.