Investigation of the relationship between COVID-19 and pancreatic cancer using bioinformatics and systems biology approaches.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, poses a huge threat to human health. Pancreatic cancer (PC) is a malignant tumor with high mortality. Research suggests that infection with SARS-CoV-2 may increase disease severity and risk of death in patients with pancreatic cancer, while pancreatic cancer may also increase the likelihood of contracting SARS-CoV-2, but the link is unclear. METHODS: This study investigated the transcriptional profiles of COVID-19 and PC patients, along with their respective healthy controls, using bioinformatics and systems biology approaches to uncover the molecular mechanisms linking the 2 diseases. Specifically, gene expression data for COVID-19 and PC patients were obtained from the Gene Expression Omnibus datasets, and common differentially expressed genes (DEGs) were identified. Gene ontology and pathway enrichment analyses were performed on the common DEGs to elucidate the regulatory relationships between the diseases. Additionally, hub genes were identified by constructing a protein-protein interaction network from the shared DEGs. Using these hub genes, we conducted regulatory network analyses of microRNA/transcription factors-genes relationships, and predicted potential drugs for treating COVID-19 and PC. RESULTS: A total of 1722 and 2979 DEGs were identified from the transcriptome data of PC (GSE119794) and COVID-19 (GSE196822), respectively. Among these, 236 common DEGs were found between COVID-19 and PC based on protein-protein interaction analysis. Functional enrichment analysis indicated that these shared DEGs were involved in pathways related to viral genome replication and tumorigenesis. Additionally, 10 hub genes, including extra spindle pole bodies like 1, holliday junction recognition protein, marker of proliferation Ki-67, kinesin family member 4A, cyclin-dependent kinase 1, topoisomerase II alpha, cyclin B2, ubiquitin-conjugating enzyme E2 C, aurora kinase B, and targeting protein for Xklp2, were identified. Regulatory network analysis revealed 42 transcription factors and 23 microRNAs as transcriptional regulatory signals. Importantly, lucanthone, etoposide, troglitazone, resveratrol, calcitriol, ciclopirox, dasatinib, enterolactone, methotrexate, and irinotecan emerged as potential therapeutic agents against both COVID-19 and PC. CONCLUSION: This study unveils potential shared pathogenic mechanisms between PC and COVID-19, offering novel insights for future research and therapeutic strategies for the treatment of PC and SARS-CoV-2 infection.

Sulforaphane triggers iron overload-mediated ferroptosis in gastric carcinoma cells by activating the PI3K/IRP2/DMT1 pathway.

OBJECTIVE: Increasing evidence indicates that prolonged exposure to sulforaphane (SFN) can improve malignancies. However, the role of iron in SFN-triggered death in gastric carcinoma cells and the underlying molecular mechanisms remain unclear. Thus, the current study explored the effects of SFN on iron overload-mediated ferroptosis and the PI3K/IRP2/DMT1 pathway in gastric carcinoma cells. METHODS: We utilized the MGC-803 cell line to assess whether SFN affected iron metabolism and whether this effect contributed to cell death. Pharmacological inhibition of iron metabolism also was performed to determine the molecular mechanism underlying SFN-triggered iron overload and the disturbance in iron metabolism. RESULTS: Our data revealed that SFN treatment altered iron homeostasis and led to iron overload in vitro. Interestingly, SFN-stimulated cell death resulted from ferroptosis, a recently identified iron-dependent form of regulated cell death. Furthermore, an iron chelator, deferiprone, ameliorated the SFN-triggered mitochondrial dysfunction and reduced the iron overload. In addition, we found that the SFN-triggered iron overload was regulated by the PI3K/IRP2/DMT1 signaling pathway. CONCLUSION: We discovered that disturbance in iron metabolism might be involved in the SFN-triggered cell death in gastric carcinoma cells. Blockade of the PI3K/IRP2/DMT1 axis could provide a feedback effect on SFN-induced ferroptosis to protect tumor cells from growth.

Association between serum baseline C1q and IgG levels and the efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma: a retrospective study.

BACKGROUND: To assess the clinical value of serum complement component 1q (C1q) and immunoglobulin G (IgG) levels in predicting the response to combined immunotherapy in patients with esophageal squamous cell carcinoma. METHODS: We conducted a retrospective study of 44 patients with esophageal squamous cell carcinoma who received combined immunotherapy in our hospital. Serum IgG and C1q levels were collected before and three weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. RESULTS: Twenty seven patients (61.4%) showed partial response (PR), 13 (29.5%) stable disease (SD), and 4 (9.1%) progressive disease (PD). None of the patients presented complete response (CR). The PR group displayed lower IgG and higher C1q levels both before and after immunotherapy than patients showing SD or PD. The IgG reduction (59.3%) and C1q increment (70.3%) in the PR group three weeks post-treatment were significantly larger than those in patients showing SD or PD. Moreover, the pretreatment C1q level and the post-treatment change of C1q levels were strongly associated with the immunotherapy response. CONCLUSIONS: High pre- and post-treatment C1q levels and reduced post-treatment IgG levels correlate with efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma. Serum baseline C1q level may predict immunotherapy response in such patients.

Characterization of a novel class A carbapenemase PAD-1 from Paramesorhizobium desertii A-3-ET, a strain highly resistant to ß-lactam antibiotics.

Although clinical antibiotic-resistant bacteria have attracted tremendous attention in the microbiology community, the resistant bacteria that persist in natural environments have been overlooked for a longtime. We previously proposed a new species Paramesorhizobium desertii, isolated from the soil of the Taklimakan Desert in China that is highly resistant to most ß-lactam antibiotics. To identify potential ß-lactamase(s) in this bacteria, we first confirmed the carbapenemase activity in the freeze-thawed supernatant of a P. desertii A-3-ET culture using the modified Hodge assay. We then identified a novel chromosome-encoded carbapenemase (PAD-1) in strain A-3-ET, using a shotgun proteomic analysis of the supernatant and genomic information. The bioinformatics analysis indicated that PAD-1 is a class A carbapenemase. Subsequent enzyme kinetic assays with purified PAD-1 confirmed its carbapenemase activity, which is similar to that of clinically significant class A carbapenemases, including BKC-1 and KPC-2. Because the location in which A-3-ET was isolated is not affected by human activity, PAD-1 is unlikely to be associated with the selection pressures exerted by modern antibiotics. This study confirmed the diversity of antibiotic-resistant determinants in the environmental resistome.

Production of taxadiene by engineering of mevalonate pathway in Escherichia coli and endophytic fungus Alternaria alternata TPF6.

Taxol (paclitaxel) is a diterpenoid compound with significant and extensive applications in the treatment of cancer. The production of Taxol and relevant intermediates by engineered microbes is an attractive alternative to the semichemical synthesis of Taxol. In this study, based on a previously developed platform, the authors first established taxadiene production in mutant E. coli T2 and T4 by engineering of the mevalonate (MVA) pathway. The authors then developed an Agrobacterium tumefaciens-mediated transformation (ATMT) method and verified the strength of heterologous promoters in Alternaria alternata TPF6. The authors next transformed the taxadiene-producing platform into A. alternata TPF6, and the MVA pathway was engineered, with introduction of the plant taxadiene-forming gene. Notably, by co-overexpression of isopentenyl diphosphate isomerase (Idi), a truncated version of 3-hydroxy-3-methylglutaryl-CoA reductase (tHMG1), and taxadiene synthase (TS), the authors could detect 61.9 ± 6.3 µg/L taxadiene in the engineered strain GB127. This is the first demonstration of taxadiene production in filamentous fungi, and the approach presented in this study provides a new method for microbial production of Taxol. The well-established ATMT method and the known promoter strengths facilitated further engineering of taxaenes in this fungus.

Clinical application of percutaneous endoscopic gastrostomy with the Introducer method using ultrathin gastroscopy / 中国内镜杂志

Objective To evaluate the clinical application and security of percutaneous endoscopic gastrostomy (PEG) with the Introducer method using ultrathin gastroseopy in dysphagia patients. Methods Clinical data of 22 cases dysphagia patients implemented with PEG with the Introducer method using ultrathin gastroseopy or conventional gastroseopy were retrospectively analyzed, the clinical effect and the complication were observed. Results 22 patients underwent PEG with the Introducer method using conventional gastroscopy (6 cases) or ultrathin gastroscopy (16 cases). Among the 16 patients underwent PEG using ultrathin gastroseopy by transnasal or peroral approach, 2 cases with trimus by received radiotherapy for nasopharyngeal cancer and 14 cases with pharyngeal or esophagus narrowing, could not completed PEG by conventional gastroscopy. The average procedure time of PEG was (12.2 ± 2.9) min in conventional gastroscopy group and (11.8 ± 3.2) min in control group. No complications were observed in these patients, but the patients in ultrathin gastroseopy group reported less discomfort associated with the procedure. 17 patients with advanced nasopharyngeal carcinoma and esophagus cancer who received PEG could completely finished 6 cycles of concurrent chemoradiotherapy. Paired-sample t test of nutrition indicators (hemoglobin, albumin and RBC) before and after the treatment showed significant difference (P < 0.05). Conclusion PEG with the introducer method using ultrathin gastroseopy is a safe and effective method of enteral nutrition, Ultrathin gastroscopy reduces the discomfort of the procedure, especially in patients with serious trimus and pharyngeal or esophagus narrowing. For patients with advanced nasopharyngeal carcinoma, preventative PEG improved the tolerance of chemoradiotherapy,reduce the incidence of adverse events.

Clinical application of percutaneous endoscopic gastrostomy with the Introducer method using ultrathin gastroscopy / 中国内镜杂志

Objective To evaluate the clinical application and security of percutaneous endoscopic gastrostomy (PEG) with the Introducer method using ultrathin gastroseopy in dysphagia patients. Methods Clinical data of 22 cases dysphagia patients implemented with PEG with the Introducer method using ultrathin gastroseopy or conventional gastroseopy were retrospectively analyzed, the clinical effect and the complication were observed. Results 22 patients underwent PEG with the Introducer method using conventional gastroscopy (6 cases) or ultrathin gastroscopy (16 cases). Among the 16 patients underwent PEG using ultrathin gastroseopy by transnasal or peroral approach, 2 cases with trimus by received radiotherapy for nasopharyngeal cancer and 14 cases with pharyngeal or esophagus narrowing, could not completed PEG by conventional gastroscopy. The average procedure time of PEG was (12.2 ± 2.9) min in conventional gastroscopy group and (11.8 ± 3.2) min in control group. No complications were observed in these patients, but the patients in ultrathin gastroseopy group reported less discomfort associated with the procedure. 17 patients with advanced nasopharyngeal carcinoma and esophagus cancer who received PEG could completely finished 6 cycles of concurrent chemoradiotherapy. Paired-sample t test of nutrition indicators (hemoglobin, albumin and RBC) before and after the treatment showed significant difference (P < 0.05). Conclusion PEG with the introducer method using ultrathin gastroseopy is a safe and effective method of enteral nutrition, Ultrathin gastroscopy reduces the discomfort of the procedure, especially in patients with serious trimus and pharyngeal or esophagus narrowing. For patients with advanced nasopharyngeal carcinoma, preventative PEG improved the tolerance of chemoradiotherapy,reduce the incidence of adverse events.

Roseomonas arcticisoli sp. nov., isolated from Arctic tundra soil.

A pale pink, Gram-reaction-negative, non-motile, aerobic bacterium, designated MC 3624T, was isolated from a tundra soil near Ny-Ålesund, Svalbard Archipelago, Norway (78° N). Growth occurred at 10-37 °C (optimum 25-30 °C) and at pH 6.0-9.0 (optimum pH 8.0). The predominant fatty acids were C16 : 0 (17.7 %), C18 : 1ω7c 11-methyl (13.4 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (10.1 %) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) (38.3 %). The major respiratory quinone was ubiquinone-10, and the main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and an unidentified aminolipids. The DNA G+C content was 68.9 mol%. Carotenoids of the spirilloxanthin series were produced. The nearest neighbour to the novel strain was Roseomonas wooponensis WW53T (94.36 % 16S rRNA gene sequence similarity). On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MC 3624T represents a novel species of the genus Roseomonas, for which the name Roseomonas arcticisoli sp. nov. is proposed. The type strain is MC 3624T (=CCTCC AB 2014278T=LMG 28637T).

Undibacterium arcticum sp. nov., isolated from arctic alpine soil.

A Gram-stain-negative, aerobic, motile rod-shaped bacterium, designated 6-67T, was isolated from a soil sample collected from Longyearbyen, Svalbard. Its taxonomic position was investigated by genotypic, phenotypic and chemotaxonomic analyses. This isolate grew at 4-28 °C (optimum, 20 °C), at pH 5.0-9.0 (optimum, pH 7.0) and with 0-0.2 % (w/v) NaCl. Strain 6-67T contained Q-8 as a major respiratory quinone and MK-7 as a minor component; the major fatty acids were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and C16 : 0. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified phospholipids and one unidentified aminophospholipid. The polyamines were putrescine and 2-hydroxyputrescine. 16S rRNA gene sequence analysis indicated that the novel strain 6-67T belonged to the family Oxalobacteraceae within the class Betaproteobacteria. The DNA G+C content of strain 6-67T was 56.21 mol%. On the basis of phylogenetic, physiological and chemotaxonomic data, strain 6-67T is considered to represent a novel species of the genus Undibacterium, for which the name Undibacterium arcticum sp. nov. is proposed. The type strain is 6-67T (=CCTCC AB 2015162T=KCTC 42986T).

Draft Genome Sequence of "Paramesorhizobium deserti" A-3-ET, a Strain Highly Resistant to Diverse ß-Lactam Antibiotics.

Here, we report the draft genome sequence of "Paramesorhizobium deserti" A-3-E(T), a strain isolated from the Taklimakan Desert of Xinjiang, China, which is resistant to multiple ß-lactam antibiotics and other antibiotics (kanamycin, erythromycin, streptomycin, etc.) as well.

Complete genome sequence of Kocuria flava strain HO-9041, a heavy metal removal bacterium from Xinjiang.

Kocuria flava HO-9041 isolated from the air of Xinjiang of China, is a Gram-positive, aerobic, coccoid, nonencapsulated, non-halophilic, and non-endospore-forming, in the genus Kocuria, and it shows the ability to remove heavy metal. Here, we report the finished and annotated genome sequence of this organism.

Chryseobacterium frigidum sp. nov., isolated from high-Arctic tundra soil, and emended descriptions of Chryseobacterium bernardetii and Chryseobacterium taklimakanense.

A yellow, Gram-reaction-negative, non-motile, aerobic bacterium, designated D07T, was isolated from a tundra soil near Ny-Ålesund, Svalbard archipelago, Norway (78° N). Growth occurred at 4-37 °C (optimum 28-30 °C) and at pH 6.0-9.0 (optimum pH 7.0-8.0). The strain produced flexirubin-type pigments. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain D07T belonged to the genus Chryseobacterium in the family Flavobacteriaceae. The 16S rRNA gene sequence of this strain showed 93.83 and 93.31 % sequence similarity, respectively, to those of Chryseobacterium contaminans C26T and Chryseobacterium taklimakanense X-65T. Strain D07T contained anteiso-C15 : 0 (25.91 %), iso-C15 : 0 (16.05 %), iso-C16 : 0 3-OH (9.64 %), iso-C16 : 0 (9.42 %) and iso-C14 : 0 (7.36 %) as the predominant cellular fatty acids, MK-6 as the major respiratory quinone and phosphatidylethanolamine, five unknown aminolipids and three unknown lipids as the main polar lipids. The DNA G+C content was 49.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain D07T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium frigidum sp. nov. is proposed. The type strain is D07T ( = CCTCC AB 2011160T = KCTC 42897T). Emended descriptions of Chryseobacterium bernardetii and Chryseobacterium taklimakanense are also provided.

Sphingoaurantiacus polygranulatus gen. nov., sp. nov., isolated from high-Arctic tundra soil, and emended descriptions of the genera Sandarakinorhabdus, Polymorphobacter and Rhizorhabdus and the species Sandarakinorhabdus limnophila, Rhizorhabdus argentea and Sphingomonas wittichii.

An orange, Gram-reaction-negative and aerobic bacterium, designated MC 3718T, was isolated from a tundra soil near Ny-Ålesund, Svalbard archipelago, Norway (78° N). The cells were motile with either a polar or a subpolar flagellum and reproduced by budding or asymmetrical cell division. Growth occurred at 4-37 °C (optimum 28-30 °C) and at pH 6.0-10.0 (optimum pH 9.0). Many cells accumulated poly-ß-hydroxybutyrate granules and contained a single large polyphosphate granule at a pole or in the middle of the cell. Cell walls contained meso-diaminopimelic acid as the diagnostic diamino acid, and ubiquinone 10 was the main respiratory quinone. Strain MC 3718T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c; 29.49 %), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 29.38 %), C17 : 1ω6c (10.15 %), C14 : 0 2-OH (9.05 %) and C16 : 0 (6.84 %) as the major cellular fatty acids. The main polar lipids were two sphingoglycolipids, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, three unknown phospholipids and two unknown polar lipids. Carotenoids were detected. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MC 3718T belonged to the family Sphingomonadaceae. The DNA G+C content was 67.2 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MC 3718T is considered to represent a novel genus and species in the family Sphingomonadaceae, for which the name Sphingoaurantiacus polygranulatus gen. nov., sp. nov. is proposed. The type strain of Sphingoaurantiacus polygranulatus is MC 3718T ( = CCTCC AB 2014274T = LMG 28636T). Emended descriptions of the genera Sandarakinorhabdus, Polymorphobacter and Rhizorhabdus and the species Sandarakinorhabdus limnophila, Rhizorhabdus argentea and Sphingomonas wittichii are also provided.

Flavobacterium collinsense sp. nov., isolated from a till sample of an Antarctic glacier.

A novel rod-shaped, Gram-stain-negative, non-gliding and aerobic strain surrounded by a multilayer capsule, designated 4-T-2T, was isolated from a till sample of Collins glacier front, Antarctica. The bacterium formed yellow, circular, convex and smooth colonies. Growth occurred at 4-28 °C (optimum18-20 °C), at pH 7.0-10.0 (optimum pH 9.0) and with 0-1 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 4-T-2T belonged to the genus Flavobacterium. Strain 4-T-2T shared the highest 16S rRNA gene sequence similarity with the type strain of Flavobacterium algicola (96.7 %). The DNA G+C content of strain 4-T-2T was 36.2 mol%. The only menaquinone was MK-6. The major cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G, iso-C16 : 0 and summed feature 9 (comprising iso-C17 : 1ω9c and/or 10-methyl C16 : 0). Polar lipid profile consisted phosphatidylethanolamine, one unidentified aminolipid, one unidentified aminophospholipid and one unidentified lipid. On the basis of phylogenetic, physiological and chemotaxonomic data, strain 4-T-2T is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium collinsense sp. nov. is proposed. The type strain is 4-T-2T ( = CCTCC AB 2014004T = LMG 28257T).

Pseudorhodobacter collinsensis sp. nov., isolated from a till sample of an icecap front.

A Gram-stain-negative, rod-shaped, aerobic and non-motile strain, designated 4-T-34T, was isolated from a till sample of Collins icecap front, Antarctica, and its taxonomic position was investigated by genotypic, phenotypic and chemotaxonomic analysis. The isolate grew at 4-30 °C (optimum 20-25 °C), at pH 6.0-10.0 and with 0-1.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 4-T-34T belonged to the genus Pseudorhodobacter, with the closest relatives being Pseudorhodobacter wandonensis WT-MW11T (96.9 % 16S rRNA gene sequence similarity), Pseudorhodobacter antarcticus ZS3-33T (96.8 %), Pseudorhodobacter ferrugineus IAM 12616T (96.5 %) and Pseudorhodobacter aquimaris HDW-19T (95.4 %). Strain 4-T-34T contained Q-10 as the only ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified aminophospholipids and two unidentified phospholipids. The DNA G+C content of strain 4-T-34T was 61 mol%. On the basis of phylogenetic, physiological and chemotaxonomic data, strain 4-T-34T is considered to represent a novel species of the genus Pseudorhodobacter, for which the name Pseudorhodobacter collinsensis sp. nov. is proposed. The type strain is 4-T-34T ( = CCTCC AB 2014005T = LMG 28256T).

Roseomonas arctica sp. nov., isolated from arctic glacial foreland soil.

A novel psychrotolerant bacterium, designed strain M6-79T, was isolated from an arctic glacial foreland soil sample collected from Ny-Ålesund in the Svalbard Archipelago, Norway. Cells of strain M6-79T were Gram-stain-negative, rod-shaped and produced a red-pigment. Strain M6-79T was strictly aerobic, non-motile, non-endospore-forming, oxidase-negative and catalase-positive. Based on 16S rRNA gene sequence analysis, strain M6-79T was phylogenetically related to Roseomonas aquatica TR53T (95.2 % 16S rRNA gene sequence similarity), Roseomonas lacus TH-G33T (94.3 %), 'Roseomonas sediminicola' FW-3 (94.3 %), Roseomonas terrae DS-48T (94.1 %) and Roseomonas soli 5N26T (94.1 %). The unique isoprenoid quinone detected in strain M6-79T was Q-9. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unknown aminolipid and one unknown lipid. Strain M6-79T possessed C18 : 1ω7c, C16 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) as the predominant fatty acids, and the DNA G+C content was 71.2 mol%. Combined data from phylogenetic, phenotypic and chemotaxonomic studies revealed that strain M6-79T represents a novel species of the genus Roseomonas, for which the name Roseomonas arctica sp. nov. is proposed. The type strain is strain M6-79T ( = CCTCC AB 2013101T = LMG 28251T).