Targeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system.

Aberrant activation of EGFR due to overexpression or mutation is associated with poor prognosis in many types of tumors. Here we show that blocking the sorting system that directs EGFR to plasma membrane is a potent strategy to treat EGFR-dependent tumors. We find that EGFR palmitoylation by DHHC13 is critical for its plasma membrane localization and identify ARF6 as a key factor in this process. N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from Golgi, and facilitates EGFR transporting to plasma membrane in a GTP-bound form. To evaluate the therapeutic potential of this sorting system, we design a cell-permeable peptide, N-myristoylated GKVL-TAT, and find it effectively disrupts plasma membrane localization of EGFR and significantly inhibits progression of EGFR-dependent tumors. Our findings shed lights on the underlying mechanism of how palmitoylation directs protein sorting and provide an potential strategy to manage EGFR-dependent tumors.

Description of a new genus and two new species of the funnel-web mygalomorph (Araneae: Mygalomorphae: Macrothelidae) from China with notes on taxonomic amendments.

A new genus of the spider family Macrothelidae Simon, 1892, Vacrothele Tang Yang gen. nov. is described, along with two new species: V. pseudohunanica sp. nov., V. uncata sp. nov.. Three Macrothele species are transferred to the new genus: V. hunanica (Zhu Song, 2000) comb. nov., V. digitata (Chen Jiang, 2020) comb. nov., and V. palpator (Pocock, 1901) comb. nov..

Two new species of the genus Pseudopoda Jäger, 2000 and first description of the male of Pseudopoda physematosa (Araneae, Sparassidae) from Yunnan Province, China.

Two new species of the genus Pseudopoda Jäger, 2000 are reported from Yunnan Province, China: Pseudopoda mingshengi sp. nov. (male, female) and P. uncata sp. nov. (male, female). The male of P. physematosa Zhang, Jäger & Liu, 2019 is described for the first time.

Alterations of the Neuroinflammatory Markers IL-6 and TRAIL in Alzheimer's Disease.

OBJECTIVE: We aimed to identify biomarkers of Alzheimer's disease (AD) in order to improve diagnostic accuracy at mild stage. METHODS: AD patients aged >50 years were included in the disease group. We evaluated the relationship between potential blood and cerebrospinal fluid inflammatory biomarkers, cognitive status, temporal lobe atrophy and disease severity. Inflammatory biomarkers including interleukin 6 (IL-6), IL-18, fractalkine and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) levels were measured. APOE genotypes were determined. RESULTS: We enrolled 41 subjects in the disease group and 40 subjects in the normal control group. The majority (88.9%) of subjects in the disease group had mild AD. Elevated levels of plasma IL-6 and decreased levels of plasma TRAIL in the disease group were noted. Plasma levels of IL-6 and TRAIL were significantly correlated with their cerebrospinal fluid levels. CONCLUSION: Plasma IL-6 and TRAIL were identified as potential biomarkers of AD at an early stage.

[Initial research on FTIR spectroscopy of lyophilized serum from colorectal cancer patients].

In the present paper, lyophilized sera from 31 patients with colorectal cancer, 8 patients with enteritis and 10 healthy controls were measured using Nicolet Nexus-670 Fourier Transform Infrared (FTIR) spectrometer, and the spectral features were investigated and comparison among three groups was made. The result showed that (1) there are 11 peaks of absorption in the spectrum of lyophilized sera, the wavenumber of the ninth peak moved to 1 249 cm(-1) in the colorectal cancer group and significant difference was observed with the control group (Z = -2.051, P < 0.05); Five ratios of absorbance were calculated and no significant difference was observed among three groups; (2) spectrum in the region of 1 700-1 000 cm(-1) was analysed with the method of hierarchical cluster analysis and showed only partial success in distinguishing the three groups; (2) spectrum of amide I peptide (1 700-1 600 cm(-1)) was deconvolved to get the percentage composition of protein secondary structures, and no significant difference was observed among three groups. The results provide a preliminary theoretical basic for using FTIR spectrum of lyophilized serum for the early diagnosis of colorectal cancer.

Clinical phenotype of G206D mutation in the presenilin 1 gene in pathologically confirmed familial Alzheimer's disease.

Familial Alzheimer's disease (FAD) is genetically heterogeneous, autosomal dominant, with nearly 100% penetrance. In FAD, most common causative genetic mutations are presenilin 1 (PSEN1), presenilin 2 and amyloid-ß protein precursor. We demonstrate a family presenting as early-onset AD with a rapid deterioration course and seizure developed after 1.5 years of symptoms. A histopathological examination of the frontal cortex showed amyloid deposition and abundant phosphorylated tau deposition. In both cases, a single nucleotide mutation from guanine to adenine at exon 7 was found in PSEN1 (c.617G>A, codon change from GGT to GAT). Though G206D mutation in PSEN1 gene was found in FAD, no clinical phenotype or pathological finding was documented. This is the first report of PSEN1 mutation (Gly206Asp) with features of seizure and a rapid progressive cognitive decline in a pathologically confirmed case of FAD.

Posterior interosseous nerve palsy as a complication of friction massage in tennis elbow.

Friction massage is a commonly used physical therapy that is usually safe and without complication. We report an unusual case of posterior interosseous nerve palsy that arose after friction massage. Electrophysiologic findings confirmed a focal neuropathy 4-6 cm distal to the lateral epicondyle. The neurologic symptoms resolved completely 2 mos after discontinuation of friction massage. This case experience broadens the spectrum of etiologies of posterior interosseous nerve palsy. Nerve conduction studies may be a useful adjunct to a thorough physical examination to confirm the diagnosis and is important to prognostic evaluation, if unexplained neurologic symptoms develop after certain physical therapy procedures. Further treatment includes avoiding compression and observation.

[Construction of eukaryotic expression plasmid pEGFP-ATP1B1 and its effect on gastric adenocarcinoma cell SGC-7901].

OBJECTIVE: To establish the eukaryotic expression plasmid containing the code gene of Na+, K+-ATPase beta1-subunit (ATP1B1) and the basis of ATP1B1 applied to antitumor gene therapy. METHODS: The ATP1B1 cDNA was amplified from leukocyte gene library and then cloned into the eukaryotic expression vector pEGFP-C3. The recombinant plasmid, named as pEGFP-ATP1B1, was determined with restriction enzyme and sequencing analyses. Next pEGFP-ATP1B1 was transferred into gastric adenocarcinoma SGC-7901 cells by lipofectamine, then ATP1B1 mRNA expression in transfected cells was detected by real-time PCR, and also ATPase was detected after cell transfection, as well as the proliferation of such cells was measured by MTT. RESULTS: The analysis confirmed that the recombinant pEGFP-ATP1B1 contained the ATP1B1 cDNA. After cell transfection, the expression of ATP1B1 mRNA(129.2%) and the activity of ATPase [(2.95+/-0.210)%] were higher, and the growth of the SGC-7901 cells transfected with ATP1B1 was inhibited obviously when compared with the control group. CONCLUSION: The recombinant pEGFP-ATP1B1 is constructed successfully, and this recombinant eukaryotic expression vector could be used in additional studies on the biological effect of ATP1B1 and its use in anti-tumor gene therapy.

[Growth inhibition and multidrug resistance-reversing effect of tanshinone I A on human breast cancer cell with estrogen receptor negative].

OBJECTIVE: To investigate the growth inhibition and multidrug resistance (MDR) reversing effect of tanshinone I A on human breast cancer cells with estrogen receptor (ER) negative, and to elucidate its mechanism of activity. METHODS: Human ER negative breast cancer cells (MDA-MB-231) were tested in vitro for cytotoxicity and colony formation inhibition. Brdu incorporation and cell cycle distribution were also checked through flow cytometry (FCM). With RT-PCR, the expressions of ADP-ribosyltransferase CNAD+; poly (ADP-ribose) polymerase)-like 1 (ADPRTL1), cytochrome P450 subfamily I (CYP1A1) and breast cancer resistance protein (BCRP/ABCG2) mRNA were detected for testing the response to tanshinone 1 A treatment. RESULTS: After tanshinone I A treatment, the proliferation, colony formation and Brdu labeling indices of cancer cells decreased (P<0. 05). By FCM analysis, the increase of subG, and G0/G1 phase cell populations and decrease of S and G2/M phase cells were observed (P