The Position of the Cytokine Profile and Cytolysis Enzymes in Patients with Viral Hepatitis before Tooth Extraction

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Рахматуллаева O., Шомуродов K., Хаджиметов A., Садикова X., & Назаров Z. (2021). The Position of the Cytokine Profile and Cytolysis Enzymes in Patients with Viral Hepatitis before Tooth Extraction. in Library, 21(1), 6558–6567. извлечено от https://inlibrary.uz/index.php/archive/article/view/14281
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Аннотация

It is known that in chronic liver diseases, secondary immunodeficiency is formed, which is of great importance for the dental system and the entire body as a whole. Therefore, it becomes clear the importance of studying the state of the protective system of oral tissues in chronic viral liver pathology, which requires timely and constant correction. The aim of this study was to evaluate the activity of proinflammatory cytokines and cytolytic enzymes in patients  with  chronic  viral  hepatitis  before  tooth  extraction.  The  level  of  cytokine  IL-1  in patients  with  CVI  before  tooth  extraction  was  on  average  43.97±3.56  pg  /  ml,  whereas  in healthy people the studied indicator was on average 5.41 ± 0.42 pg / ml. The patients showed an increase in the level of IFN in the blood serum by an average of 6.2 times, the level of interleukin-18, belonging to the IL-1 family, was statistically significantly increased by 2.4 times  in  patients  with  CVI,  compared  with  the  control  group.  The  features  of  CVH  are dissociations  between  the  levels  of  proinflammatory  cytokines  IL-1,  IL-6,  IL-18  and interferon.  This  indicates  the  disintegration  of  the  inflammatory  process  occurring  in  the periodontal tissues and with the transition to a chronic course of the disease. Changes in the level of IL-1, IL-6, IL-18 and interferon in the blood serum of patients with CVI from normal parameters before tooth extraction is an indicator of the severity of the inflammatory process in the liver, as evidenced by changes in the dynamics of cytolytic enzymes.

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Annals of R.S.C.B., ISSN: 1583-6258, Vol. 25, Issue 1, 2021, Pages. 6558 – 6567
Received 15 December 2020; Accepted 05 January 2021.


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The Position of the Cytokine Profile and Cytolysis Enzymes in Patients

with Viral Hepatitis before Tooth Extraction

O.U.Rakhmatullaeva

1

, Kh.E.Shomurodov

2

, A.A.Hadjimetov

3

, X.Kh.Sadiqova

4

,

Z.Z.Nazarov.

5

Tashkent State Dental Institute

Abstract.

It is known that in chronic liver diseases, secondary immunodeficiency is formed,

which is of great importance for the dental system and the entire div as a whole. Therefore,
it becomes clear the importance of studying the state of the protective system of oral tissues
in chronic viral liver pathology, which requires timely and constant correction. The aim of
this study was to evaluate the activity of proinflammatory cytokines and cytolytic enzymes in
patients with chronic viral hepatitis before tooth extraction. The level of cytokine IL-1 in
patients with CVI before tooth extraction was on average 43.97±3.56 pg / ml, whereas in
healthy people the studied indicator was on average 5.41 ± 0.42 pg / ml. The patients showed
an increase in the level of IFN in the blood serum by an average of 6.2 times, the level of
interleukin-18, belonging to the IL-1 family, was statistically significantly increased by 2.4
times in patients with CVI, compared with the control group. The features of CVH are
dissociations between the levels of proinflammatory cytokines IL-1, IL-6, IL-18 and
interferon. This indicates the disintegration of the inflammatory process occurring in the
periodontal tissues and with the transition to a chronic course of the disease. Changes in the
level of IL-1, IL-6, IL-18 and interferon in the blood serum of patients with CVI from normal
parameters before tooth extraction is an indicator of the severity of the inflammatory process
in the liver, as evidenced by changes in the dynamics of cytolytic enzymes.

Keywords

: viral hepatitis, tooth extraction, cytokines, enzymes.

INTRODUCTION

With any surgical intervention in the oral cavity, an unsatisfactory level of oral hygiene and
inflammatory periodontal diseases significantly increase the risk of general infectious
complications caused by pathogenic periodontal microflora.An important role in the
development of complications during surgical manipulations in the oral cavity is played not
only by microbial toxins, but also by viral intoxication. Viral hepatitis both in our country
and abroad occupies a significant place in the general human pathology, causing significant
socio-economic damage to society. Among the important problems of modern practical
dentistry are the issues of improving the diagnosis, prevention and treatment of complications
after tooth extraction in patients with chronic viral hepatitis, which remain relevant to the
present time and have great social significance. As is known, after tooth extraction, the filling
of the wound space with granulation tissue begins approximately four days after the injury.
At this time, macrophages, fibroblasts, and new capillaries appear in the wound. Blood
vessels provide the delivery of oxygen and nutrients to the cells of the new stroma.
Macrophages are the main source of growth factors that stimulate fibroblasts and
angiogenesis. Cytokines produced at this stage of wound healing mainly affect fibroblast
proliferation and / or collagen production, as well as extracellular matrix production.


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Annals of R.S.C.B., ISSN: 1583-6258, Vol. 25, Issue 1, 2021, Pages. 6558 – 6567
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Interleukin-1 (IL-1), being the most important mediator of the development of inflammation,
has a wide range of biological activity and stimulates the functions of almost all cells
involved in protective reactions, including cells of the central nervous, endocrine and
hematopoietic systems. Cytokine synthesis begins in response to tissue damage or infection.
The main cells that produce IL-1 in the div are monocytes and macrophages, as well as
cells that share a common origin with macrophages. IL-1 is also produced by fibroblasts,
lymphocytes, NK cells, keratinocytes, endothelial cells, and neutrophils. The IL-1 action can
be implemented both at the system level and at the local level. Since almost all cells in the
div have receptors for IL-1, this cytokine very quickly activates almost all types of cells
involved in the formation of a local inflammatory response. At the systemic level, IL-1
causes activation of the neuro-endocrine system, affects immunopoiesis, immunostimulation,
synthesis of acute-phase proteins in the liver, and stimulation of bone marrow hematopoiesis.
At the local level, IL-1 can regulate the functions of virtually all cell types involved in local
inflammation and repair. The role of IL-1 and other cytokines in the development of local
inflammation and wound healing is currently of great interest to researchers. The increased
production of IL-1 in the early stages of wound healing serves to trigger the cascade of
synthesis of other cytokines and growth factors, as well as to regulate and coordinate the
functions of cells involved in the wound process. IL-1 can stimulate the growth and
metabolism of connective tissue, as well as the re-epithelization of wounds. The main causes
of wound healing complications in these cases are ischemia, neuropathy, and infections.
When the wound heals, a massive formation of new blood vessels occurs in the granulation
tissue. The main causes of delayed wound healing in inflammatory processes, especially in
the combination of its pathology of viral etiology, are prolonged inflammation on the one
hand, and a decrease in reparative processes in wounds on the other. At the same time, there
is a dysregulation of the production of chemotactic factors for white blood cells, which leads
to a prolonged presence of neutrophils and macrophages in the wound and an elongation of
the inflammatory phase of the wound process. Thus, IL-1 is one of the most important
cytokines that regulate the local inflammatory process and wound healing.

Interleukin-18 (IL-18) belongs to the interleukin-1 family, it is also, like interleukin-1, a
mediator of inflammation. Interleukin-18 (IL-18) occupies a special position among
immunoregulatory mediators, as it is one of the key cytokines involved in the formation of
innate and acquired immune responses. Having the ability to stimulate the production of IFN-
y adhesion molecules and apoptosis factors. IL-18 is involved in the activation of cytotoxic
T-lymphocytes, NK cells, macrophages, and dendritic cells and contributes to the formation
of an effective anti-infective immune response. Nevertheless, the most pronounced activity of
IL-18 is considered to be the ability to stimulate the differentiation of the Th1 type and their
production of IFN-y, which ultimately leads to the activation of the cellular link of the
immune response, which is necessary in the case of infectious processes (viral and bacterial).
Currently, the coordinating role of proinflammatory IL-18 as an additional stimulator of
interferon production (primarily interferon-γ), which largely determines the antiviral defense
of the div, has been established.IL-18 is involved in the antiviral defense of the div, in
particular, in the formation of an immune response against hepatitis B virus antigens. The
protective immune response during viral hepatitis B (HBV) is associated with the induction


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of the cellular link of the immune system and is implemented through type 1 T helper cells.
The presentation of the antigen and the determination of the type of immune response is
carried out by antigen-presenting cells, in particular, dendritic cells (DC). The direction of
immune responses is determined by the profile of cytokines produced by DC. Important in
the pathogenesis of chronic viral hepatitis B are proinflammatory cytokines (INF-Y, IL-1,
TNF) and, in particular, IL-18. IL-18 has been shown to inhibit viral hepatitis replication in
the liver of transgenic mice. On the other hand, an increase in the level of endogenous IL-18
in chronic liver diseases is associated with the activation of mechanisms of immune damage
to the liver mediated through the fas ligand.

In the acute phase of inflammation, the synthesis of more than 40 proteins increases, which,
depending on the nature of the stimulus, have pro-inflammatory or anti-inflammatory
properties. C-reactive protein, the main protein of the acute phase of inflammation, binds
various pathogenic factors and decay products of damaged cells, promotes opsonization of
these substances and activates the complement system. From this point of view, the increase
in the synthesis of acute phase proteins under the influence of IL-6 can be considered a
protective mechanism that limits tissue damage. Increased IL-6 production is often associated
with tissue damage: infections, immune hypersensitivity reactions, and autoimmune diseases.
IL-6 is one of the main mediators of such clinical and laboratory manifestations of tissue
damage, leukocytosis, an increase in the blood level of proteins of the acute phase of
inflammation and a decrease in the level of albumin. IL-6 stimulates the development of
plasmocytosis and hypergammaglobulinemia, and also activates the hypothalamic-pituitary-
adrenal system.

It is known that in chronic liver diseases, secondary immunodeficiency is formed, which is of
great importance for the dental system and the entire div as a whole. Therefore, it becomes
clear the importance of studying the state of the protective system of oral tissues in chronic
viral liver pathology, which requires timely and constant correction. In the available
literature, there are few publications on the state of periodontal tissues and oral mucosa in
patients with viral hepatitis, but studies of the cytokine profile and the enzyme status of blood
in surgical patients before tooth extraction were not studied at all, which was the reason for
choosing this research topic. The aim of this study was to evaluate the activity of
proinflammatory cytokines and cytolytic enzymes in patients with chronic viral hepatitis
before tooth extraction.

RESEARCH MATERIALS AND METHODS

58 patients with chronic viral hepatitis were examined. The studies were conducted in strict
accordance with the requirements of biomedical ethics in accordance with the Geneva
Convention on Human Rights (1997) and the Helsinki Declaration of the World Medical
Association (2000), based on the permission of the local ethics committee. In the group with
chronic hepatitis, patients were divided by gender as follows: men-58%, women-42%, the
average age of patients was 35.6±10.7 years. All patients received written voluntary informed
consent to participate in the study. Inclusion criteria: verified diagnosis of chronic viral
hepatitis B and C detected by polymerase chain reaction (PCR) using a test system, patients


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who did not receive antiviral therapy. Exclusion criteria: patients under 18 years of age with
concomitant viral hepatitis D or other diseases that cause liver damage, HIV infection, a
history of pulmonary tuberculosis, autoimmune, oncological diseases, as well as pregnant
women. In order to determine the control values of the studied parameters of the hemostasis
system, 16 practically healthy individuals aged 25 to 45 years, who gave informed consent to
the examination, did not differ from patients by sex and age, did not have a history, the
results of biochemical and serological studies of viral hepatitis, as well as other liver diseases,
were examined. The following instrumental studies were used: ultrasound examination of the
abdominal organs, clinical and laboratory methods (determination of total and direct
bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline
phosphatase, gammaglutamyltranspeptidase (GGTP), homocysteine, total protein and protein
fractions, cholesterol, amylase, urea, creatinine. Indication of HCV-PHK, determination of
the virus genotype, the level of viral load by polymerase chain reaction (PCR). The indicated
cytokines IL-1,6,18 and Y-interferon in blood serum were determined by the method of
enzyme immunoassay using reagent kits (manufacturer of CJSC Vector-Best, Russia).The
optical density measurement and calculation of the results were carried out on a COBAS-411
photometer according to the attached instructions, the results were expressed in pg / ml.
Cnfnbcnbxtcrbq f analysis was carried out using modern statistical analysis packages:
statgraphicsPlusfor Windows version 4.0, Statisticafor Windows version 8.0. Statistical
methods of descriptive statistics, correlation analysis, and establishing the reliability of the
difference between the data in the main and control groups based on the calculation of the
Student's criterion were used. The data in the text and tables are given as M±m(mean value ±
standard error of the mean value). The results with a significance level of <0.05 (95%
confidence interval) were taken as reliable.

RESEARCH RESULTS AND DISCUSSION

As is known, the pathogenesis of chronic viral hepatitis (CVI) is based on deep violations of
the immune response with an imbalance in the quantitative and qualitative composition of
immunocompetent cells, with a violation of their functional activity and cellular cooperation.
The features of the immune response have a relationship with the ratio of cytokines produced
by immunocompetent cells, so in the study of the pathogenesis of chronic viral hepatitis, a
qualitative and quantitative assessment of the cytokine profile is of great importance. The
results of numerous studies indicate that cytokines play an important role in the control of
viral replication, damage processes, inflammatory infiltration, regeneration, and liver fibrosis.

To diagnose and predict the course of chronic hepatitis of viral etiology, we used the
definition of AlAT, AsAT CRP. The presence of cytolytic syndrome was judged by the
change in the AlAT level, which was on average 139.52±9.78 IU/l in patients with CVI,
while the AlAT values in the comparison group were 18.63±1.74 IU/ l, and by the AsAT
level, the concentration of which was 118.41±9.78 IU/l in patients with CVI, compared to
15.42±1.13 IU/l in the group of healthy individuals. A similar dynamics was observed with
respect to the C-reactive protein, where its concentration exceeded the initial indicator by 25
times.


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A sufficient range of cytokines was studied to characterize the immune response in patients
with CVH. It included a group of proinflammatory cytokines produced in response to the
direct action of the virus: IL-1, IL-6, IL-18, and a regulator of immune inflammation: Y-
Interferon.

Since the intensity of viral replication is not always associated with the severity of the
inflammatory response and clinical manifestations of viral hepatitis, we studied the cytokine
profile in patients with CVI, which is presented in Table 1. Interleukin-1 (IL-1) is known to
be one of the main cytokines responsible for the development of a local inflammatory
response and an acute phase response at the level of the entire div. IL-1 is a multifunctional
cytokine that plays a key role in the development and regulation of non-specific defense and
is one of the first to be included in the div's defense response when exposed to pathogenic
factors. IL-1, produced by phagocytes in the lesion site, triggers the synthesis of acute liver
phase proteins (CRP) and participates in the neuro-endocrine stimulation of protein synthesis.

The analysis of the results of the studies presented in Table-1 showed that the level of
cytokine IL-1 in patients with CVI before tooth extraction was on average 43.97±3.56 pg /
ml, while in healthy people the studied indicator was on average 5.41 ± 0.42 pg / ml. In our
opinion , the highest production of IL-1 in the blood serum of the examined patients with
CHB is associated with the activation of macrophages. The results obtained confirm the
literature data on the increase of this cytokine in patients with CHB as a mediator reflecting
the intensity of inflammation.

Table 1

Values of biochemical parameters and proinflammatory cytokines in

patients with viral hepatitis before tooth extraction


Indicators

Healthy person
n=16

Patients

with

viral

hepatitis
n=58

1 ASAT ( U/l)

15,42±1,13

118,41±9,78*

2 Alat (U/l)

18,63±1,74

139,52±10,24*

3 CRP (mg/l)

0,75±0,06

18,63±1,33*

IFN-γ (PG/ml)

3,86±0,28

23,84±1,21*

IL-18 (PG/ml)

173,58±10,21

421,62±11,75*

IL-1β (PG/ml)

5,41 ± 0,42

43,97±3,56*

IL-6 ( PG/ml)

5,13± 0,39

48,71±3,48*

Note: * - the significance of differences P< 0.05 relative to the indicators
comparison groups
As is known, IL-1 and IL-6 are involved in the implementation of many local and systemic
manifestations of the inflammatory response. IL-6 is an acute phase protein and at the same
time causes the synthesis of acute phase proteins in the liver. IL-6 contributes to both


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exacerbation of chronic and chronic acute inflammatory processes. It increases in the blood
during any inflammatory processes. When determining the concentration of anti-
inflammatory cytokines IL-6 in patients with CVI, there was a significant increase in their
level compared to the control group. If we take into account that IL-6 is synthesized by
activated macrophages in response to inflammation and tissue necrosis, then its high values in
this cohort of patients also confirm the exacerbation of chronic viral pathology during tooth
extraction. It can be assumed that the increased level of proinflammatory cytokines IL-1,6 in
the blood serum of the examined individuals is due to the stimulation of mononuclear
phagocytes and an increased cytotoxic reaction, which results in the elimination of the viral
hepatitis antigen by hepatocytes in patients with CVI. In our opinion, the studied indicators of
the cytokine system can be used as important diagnostic criteria before tooth extraction in
patients with CVI.
The content of proinflammatory cytokine, namely, interferon-alpha (INF-α), which plays a
key role in the antiviral defense of the div, was increased in patients with CVI. IFN-Y is an
endogenous modulator, a type II inductor. According to the literature, IFN-U plays a central
role in the development of chronic inflammation. It enhances the action of TNF-A by a
number of cells. IFN-promotes the production of IL-8, activates the synthesis of acute phase
proteins by liver cells. In chronic viral hepatitis, the observed patients showed an increase in
the level of IFN in the blood serum by an average of 6.2 times, relative to the indicators of
healthy individuals.

The level of interleukin-18, belonging to the IL-1 family, was statistically significantly
increased by 2.4 times in patients with CVI, compared with the control group. An increase in
the proinflammatory cytokine IL-18 characterizes the presence of immune inflammation at
the systemic level due to the stimulation of hepatocytes. At the same time, there was also a
significant increase in C-reactive protein (CRP). Consequently, the predominance of
proinflammatory cytokines in individuals with CVH occurs within the framework of the
acute phase reaction, as evidenced by a 25-fold increase in the concentration of C-reactive
protein. An increase in IL-18 and CRP, as well as liver cytolytic enzymes (AlAT and AsAT),
may indicate immune-mediated damage associated with a high rate of virus mutation, IL-18
gene polymorphism, leading to massive synthesis of pro-inflammatory cytokines by immune-
competent cells and activating cytotoxic effector mechanisms that lead to liver damage
(cytolysis syndrome).

Thus, the increased content of cytokines IL-1, IL-6, IL-18, IFN-Y, and their excessive
activity can become a factor in the progression of the pathological process, which is observed
in most patients with CVI. Excessive concentration of cytokines has a direct damaging effect
on parenchymal cells, i.e. it is associated with cytotoxic and destructive effects observed in
patients with CVI. Studies have shown that as the immune-inflammatory process develops,
cytokines exhibit pro-inflammatory properties; they activate the proliferation of T-
lymphocytes, increase the level of activation of the mononuclear phagocytosis system, and
increase the adhesion of neutrophils to the endothelium. It can be assumed that the increased
level of proinflammatory cytokines is due to the stimulation of mononuclear phagocytes and


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an increased cytotoxic reaction, which results in the elimination of the virus antigen of
infected hepatocytes in patients with CVI.

CONCLUSION

1. An increase in IL-1 in patients with CVI before tooth extraction is an important prognostic
criterion, since it is involved not only in inflammatory processes, but also in destructive
processes.

2. The features of CVH are dissociations between the levels of proinflammatory cytokines
IL-1, IL-6, IL-18 and interferon. This indicates the disintegration of the inflammatory process
occurring in the periodontal tissues and with the transition to a chronic course of the disease,
which indicates the implementation of appropriate preventive measures.

3. It should be noted that changes in the level of IL-1, IL-6, IL-18 cytokinesand interferon in
the blood serum of patients with CVI from normal parameters before tooth extraction is an
indicator of the severity of the inflammatory process in the liver, as evidenced by changes in
the dynamics of cytolytic enzymes.

4.The obtained research results make it possible to use these indicators as important
diagnostic criteria for the progressive course of chronic pathology not only of the liver but
also of periodontal tissues.

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Bazarova D. Some problems of counteracting crimes related to laundering of illegal
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Systems. Volume 11,
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Ismailova, Z., Choriev, R., Ibragimova, G., Abdurakhmanova, S., &Abdiev, N. (2020).
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background image


Annals of R.S.C.B., ISSN: 1583-6258, Vol. 25, Issue 1, 2021, Pages. 6558 – 6567
Received 15 December 2020; Accepted 05 January 2021.


6567

http://annalsofrscb.ro

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Isakov, A., Tukhtamishev, B., &Choriev, R. (2020). Method for calculating and
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Davirov, A., Tursunov, O., Kodirov, D., Baratov, D., &Tursunov, A. (2020). Criteria
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and Environmental Science, 2020, 614(1), 012039

[35]

Obidov, B., Choriev, R., Vokhidov, O., &Rajabov, M. (2020). Experimental studies of
horizontal flow effects in the presence of cavitation on erosion-free dampers. IOP
Conference Series: Materials Science and Engineering, 883(1), 012051

[36]

Khasanov, B., Choriev, R., Vatin, N., &Mirzaev, T. (2020). The extraction of the water-
air phase through a single filtration hole. IOP Conference Series: Materials Science and
Engineering, 2020, 883(1), 012206

[37]

Shokhrud F. Fayziev The problem of social stigma during a pandemic caused by
COVID-19 International Journal of Advanced Science and Technology Vol. 29, No. 7,
(2020), pp. 660-664

http://sersc.org/journals/index.php/IJAST/article/view/13965/7188

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FayziyevShokhrudFarmonovich Medical law and features of legal relations arising in
the provision of medical services. International journal of pharmaceutical research
Volume 11, Issue 3, July - Sept, 2019 P. 1197-1200 doi:10.31838/ijpr/2019.11.03.088

http://www.ijpronline.com/ViewArticleDetail.aspx?ID=11016

[39]

Bryanskaya Elena, FayzievShokhrud, Altunina Anna, MatiukhaAlena Topical Issues of
an Expert Report in the Process of Proving in a Criminal Examination. International
Journal of Engineering and Advanced Technology (IJEAT) ISSN: 2249 – 8958,
Volume-9 Issue-1, October 2019 5345-5349 DOI: 10.35940/ijeat.A2946.109119

[40]

https://www.ijeat.org/wp-content/uploads/papers/v9i1/A2946109119.pdf

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FayzievShokhrud (2019) Legal Aspects of Transplantology in the Republic of
Uzbekistan. Systematic Reviews in Pharmacy, ISSN: 0976-2779, Vol: 10, Issue: 2,
Page: 44-47 doi:10.5530/srp.2019.2.08

[42]

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Tulaganova, G.Some issues of observance of international legal norms of fight against
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Research in Dynamical and Control Systems
12(2 Special Issue), с. 143-155

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Ismailova, Z., Choriev, R., Salomova, R., &Jumanazarova, Z. (2020). Use of economic and geographical methods of agricultural development. Journal of Critical Reviews. Innovare Academics Sciences Pvt. Ltd. https://doi.org/10.31838/jcr.07.05.84

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Obidov, B., Choriev, R., Vokhidov, O., &Rajabov, M. (2020). Experimental studies of horizontal flow effects in the presence of cavitation on erosion-free dampers. IOP Conference Series: Materials Science and Engineering, 883(1), 012051

Khasanov, B„ Choriev, R„ Vatin, N.. &Mirzaev, T. (2020). The extraction of the waterair phase through a single filtration hole. IOP Conference Scries: Materials Science and Engineering, 2020, 883(1), 012206

Shokhrud F. Fayziev The problem of social stigma during a pandemic caused by COVID-19 International Journal of Advanced Science and Technology Vol. 29, No. 7, (2020), pp. 660-664 http://sersc.org/ioumals/index.php/IJAST/article/view/13965/7188

FayziyevShokhrudFarmonovich Medical law and features of legal relations arising in the provision of medical services. International journal of pharmaceutical research Volume 11, Issue 3, July - Sept, 2019 P. 1197-1200 doi: 10.31838/ijpr/2019.11.03.088 http://www.ijpronline.com/View ArticleDetail.aspx?lD= I1016

Bryanskaya Elena, FayzicvShokhrud, Altunina Anna, MatiukhaAlcna Topical Issues of an Expert Report in the Process of Proving in a Criminal Examination. International Journal of Engineering and Advanced Technology (IJEAT) ISSN: 2249 - 8958, Volume-9 Issue-1, October 2019 5345-5349 DOI: 10.35940/ijeat.A2946.109119

https://www.iieat.org/wp-content/uploads/papers/v9il/A2946109119.pdf

FayzievShokhrud (2019) Legal Aspects of Transplantology in the Republic of Uzbekistan. Systematic Reviews in Pharmacy, ISSN: 0976-2779, Vol: 10, Issue: 2, Page: 44-47 doi: 10.5530/srp.2019.2.08

http://www.svsrevphann.Org//fulltext/l 96-1575419211 .pdf? 1586863081

Tulaganova, G.Somc issues of observance of international legal norms of fight against legalization of criminal incomes in the Republic of UzbekistanJoumal of Advanced Research in Dynamical and Control Systems 12(2 Special Issue), c. 143-155

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