Publications by authors named "A V Bazhin"

147 Publications

Experimental postoperative ileus: is Th2 immune response involved?

Int J Med Sci 2021 16;18(13):3014-3025. Epub 2021 Jun 16.

Department of General, Visceral, and Transplantation Surgery, University Hospital, LMU Munich, 81377, Munich, Germany.

Postoperative ileus (POI) is a frequent complication arising after gastrointestinal surgery but pathogenesis of POI is still not fully understood. While Th1 immune cells are implicated in POI, the involvement of Th2 cells has not yet been clarified. Given the impact of reactive oxygen species (ROS) in the regulation of Th1 and Th2 balance, we hypothesized that not only Th1 but also Th2 immune response can be involved in the development of experimental POI. The intestinal transit test was performed using carbon gum arabic. Electron microscopy was employed to assess tissue morphology and the presence of immune cells. Cytokines, IgE and ROS were measured. Immune cells from Peyer's patches were analyzed by Flow Cytometry and toluidine blue staining was used for detection of mast cells. Transcriptional factors were analyzed by Western blot. POI is associated with an increase in both Th2 cytokines and Th2 cells. We have further demonstrated that POI induces a Th2-dependent activation of memory and non-memory B cells. This was accompanied by an increase in a number of mast cells in the colon of POI mice as well by an increased IgE and histamine plasma levels. We found that POI-induced accumulation of ROS was associated with an increased expression of the transcriptional factors HMBGI, NF-κB, and p38. This increased expression seemed to be associated with a Th2 response. Th2 immune response can be involved in the activation of mast cells in POI, which was associated with ROS mediated activation of NF-κB and p38 MAPK signaling pathway.
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http://dx.doi.org/10.7150/ijms.59354DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241774PMC
June 2021

Influence of the Microbiota of the Cryolithozone Paleoecosystems on the Behavioral Functions of the Nervous System of Chickens Gallus gallus.

Bull Exp Biol Med 2021 May 26;171(2):234-237. Epub 2021 Jun 26.

Federal Research Center Tyumen Scientific Center, Siberian Division of Russian Academy of Sciences, Tyumen, Russia.

We studied the influence of microorganisms isolated from permafrost on the psychophysiological parameters of birds. Significant effect of the microbiota of the paleoecosystems of the cryolithozone on locomotor activity, psycho-emotional state, and psychophysiological lateralization of brain function of Gallus gallus chickens. The involvement of both the autonomic and the higher central nervous systems in this regulatory process via synthesis of neuropeptides by symbionts is discussed.
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http://dx.doi.org/10.1007/s10517-021-05201-8DOI Listing
May 2021

Identification of the Neurokinin-1 Receptor as Targetable Stratification Factor for Drug Repurposing in Pancreatic Cancer.

Cancers (Basel) 2021 May 30;13(11). Epub 2021 May 30.

Department of General, Visceral and Transplantation Surgery, University Hospital, Ludwig-Maximilians-University Munich, 81377 Munich, Germany.

The SP/NK1R-complex plays an important role in tumor proliferation. Targeting of the neurokinin-1 receptor in previous studies with its antagonist aprepitant (AP) resulted in anti-tumoral effects in colorectal cancer and hepatoblastoma. However, there is still a lack of knowledge regarding its effects on pancreatic cancer. Therefore, we treated human pancreatic ductal adenocarcinoma (PDAC) cell lines (Capan-1, DanG, HuP-T3, Panc-1, and MIA PaCa-2) and their cancer stem cell-like cells (CSCs) with AP and analyzed functional effects by MTT-, colony, and sphere formation assays, respectively; moreover, we monitored downstream mechanisms by flow cytometry. NK1R inhibition resulted in dose-dependent growth reduction in both CSCs and non-CSCs without induction of apoptosis in most PDAC cell lines. More importantly, we identified striking AP dependent cell cycle arrest in all parental cells. Furthermore, gene expression and the importance of key genes in PDAC tumorigenesis were analyzed combining RT-qPCR in eight PDAC cell lines with publicly available datasets (TCGA, GEO, CCLE). Surprisingly, we found a better overall survival in patients with high NK1R levels, while at the same time, NK1R was significantly decreased in PDAC tissue compared to normal tissue. Interestingly, there is currently no differentiation between the isoforms of NK1R (truncated and full; NK1R-tr and -fl) in any of the indicated public transcriptomic records, although many publications already emphasize on important regulatory differences between the two isoforms of NK1R in many cancer entities. In conclusion, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies. Furthermore, we presume PDAC patients with high expressions of NK1R-tr might benefit from treatment with AP to improve chemoresistance. Therefore, analysis of splice variants might potentially lead to a stratification of PDAC patients for NK1R-directed therapies.
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http://dx.doi.org/10.3390/cancers13112703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198055PMC
May 2021

Portable bioluminescent platform for in vivo monitoring of biological processes in non-transgenic animals.

Nat Commun 2021 05 11;12(1):2680. Epub 2021 May 11.

Institute of Chemical Sciences and Engineering (ISIC), Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.

Bioluminescent imaging (BLI) is one of the most powerful and widely used preclinical imaging modalities. However, the current technology relies on the use of transgenic luciferase-expressing cells and animals and therefore can only be applied to a limited number of existing animal models of human disease. Here, we report the development of a "portable bioluminescent" (PBL) technology that overcomes most of the major limitations of traditional BLI. We demonstrate that the PBL method is capable of noninvasive measuring the activity of both extracellular (e.g., dipeptidyl peptidase 4) and intracellular (e.g., cytochrome P450) enzymes in vivo in non-luciferase-expressing mice. Moreover, we successfully utilize PBL technology in dogs and human cadaver, paving the way for the translation of functional BLI to the noninvasive quantification of biological processes in large animals. The PBL methodology can be easily adapted for the noninvasive monitoring of a plethora of diseases across multiple species.
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http://dx.doi.org/10.1038/s41467-021-22892-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113525PMC
May 2021

The predictive value of tumor infiltrating leukocytes in Hepatocellular Carcinoma: A systematic review and meta-analysis.

Eur J Surg Oncol 2021 May 4. Epub 2021 May 4.

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. Electronic address:

Background: For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS).

Material And Methods: A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3, CD8, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis.

Results: Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3, CD8, NK-cell infiltration predicted better survival (OS, DFS and RFS; p < 0.05). Higher Treg and Neutrophil infiltration predicted lower OS and DFS. For Macrophages and B cells no difference in survival could be found.

Discussion: As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.
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http://dx.doi.org/10.1016/j.ejso.2021.04.042DOI Listing
May 2021
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