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Table of Contents
April-June 2022
Volume 6 | Issue 2
Page Nos. 159-294
Online since Friday, June 17, 2022
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REVIEW ARTICLES
Molecular facets and biochemical cross-talk of angiogenesis: Potential therapeutic targets
p. 159
Jinnenahalli Raju Yodhaanjali, Raghu Ram Achar
DOI
:10.4103/bbrj.bbrj_248_21
Angiogenesis is a well conserved biological process for vascular growth and development. A canonical approach towards angiogenesis as provided insight in understanding the molecular and biochemical mechanism which differs in cancer angiogenesis. Vascular sprouting is a critical process in cancer metastasis and invasion, cancer cells release certain growth factors that can activate downstream signalling pathways to initiate VEGFR2 gene transcription further instigating angiogenesis via VEGFR2 receptors. Furthermore, paracrine signalling through these growth factor can directly bind to VEFGR2 causing its activation. There are several factors that has been procured by cancerous cells to sustain its survival. Over a period, studies have shown that there are various downstream signalling pathways taking part in cancer prognosis as most of the signalling pathways aim to inhibit endogenous VEGFR2 inhibitory molecules such as Thrombospondin. Cancer is a multifactorial disease and therefore hypoxia, changes in cellular pH, metabolic reprogramming, mutations in proto-oncogenes and tumour suppressor genes have been the contributory factors for cancer cell growth. Understanding the biochemical and molecular mechanism have paved its way in unsnarling the potential therapeutic targets. In addition, the role of adhesion molecules has also been studies they act as an adaptor molecule for an example αvβ6 in hippo pathway activates VEGFR for tip cell activity. Thereafter, focusing on these aspects of angiogenesis can provide several targets that would be used for developing and designing inhibitory antagonist, oncogene targeting drugs or anti-cancer drugs.
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Itraconazole and posaconazole from antifungal to antiviral drugs
p. 164
Falah Hasan Obayes AL-Khikani
DOI
:10.4103/bbrj.bbrj_242_21
The extended spectrum of antifungal triazole such as posaconazole (POS) and itraconazole (ITZ) shows the active efficacy for prophylaxis and treatment of an invasive fungal infection that may cause various infections such as respiratory diseases. Active azoles' derivatives, especially POS and ITZ, with high biological efficacy and low toxicity have made new advances in azoles' compounds as antimicrobials. Recently, some studies focused on the potential antimicrobial action of POS and ITZ against some viruses such as influenza A virus, Ebola virus, and enteroviruses. In general, new treatment research is needed due to the continued expansion of viral diseases and the exponential growth in mortality rates. By discussing the most recent information about the antiviral action of POS and ITZ against certain viral infections, as well as attempting to gain a deep understanding of the major properties, mechanisms of action, immune system responses, and antimicrobial activity of POS and ITZ, this review may serve as an impetus for researchers working in the field of medical microbiology and antiviral drug design. Since the antiviral activity of POS and ITZ against various viruses by different mechanisms of actions including enveloped viral infection, besides its other unique properties such as prophylactic feature and host immunomodulatory effects, as a result of our review, it appears that POS and ITZ, as effective antifungi drugs, may offer the possibility of developing a novel therapeutic alternative or synergistic treatment for certain viruses.
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ORIGINAL ARTICLES
Impact of Proinflammatory Cytokines: (Interleukin 6, Interleukin 1α, and Interleukin 1β) on Biochemical Parameters in Severe Acute Respiratory Syndrome Coronavirus 2 Patients in Iraq
p. 170
Ismael Raheem Al-Muhana, Mohanad Mohsin Ahmed, Ishaq Raheem Al-Muhana, Baraa Akeel AL-Hasan
DOI
:10.4103/bbrj.bbrj_249_21
Background:
The cytokine storm and specific biochemical results were both observed during Coronavirus disease 2019 (COVID-19) infection. The aim of this study was to see if there was any correlation between biochemical findings and cytokine levels.
Methods:
A total of 65 COVID-19 patients, including 32 males and 33 females with ages between (16 and 90 years) were enrolled in this study. Between December 2020 and February 2021, these patients were admitted to Al-Amal Specialized Hospital or ward of COVID-19 care in Al-Sader Hospital. These patients were classified into severe/critical (43 cases), mild/moderate (22 cases) according to the guidelines released by National Health World depending on SpO
2
percentage. The biochemical indices were measured using FUJI DRI-CHEM NX500 automated clinical chemistry analyzer (FUJIFILM, Japan). The proinflammatory cytokine (interleukin-6 [IL-6], IL-1α, and IL-1β) were measured using ELISA technique.
Results:
IL-6 serum levels were negatively correlated with SpO2 (P = 0.002, R = - 0.372) and serum albumin (P = 0.034, R = - 0.301). IL-1α serum levels showed significant negative correlation with serum albumin levels (P = 0.039, R = - 0.259). Furthermore, a positive correlation found between IL-1β serum with serum levels of both AST and LDH (P = 0.049; R = 0.255; P = 0.054; R = 0.320 respectively).
Discussion:
Increased IL-6 serum levels have a direct impact on SpO2 percentage and serum albumin. Whereas the elevated levels of both IL-1α and IL-1β are a possible cause of acute inflammation and liver damage in COVID-19.
Conclusions:
This study further confirms the growing evidence on the direct role of proinflammatory cytokines in the biochemical changes shown in COVID-19.
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Evaluation of biofilm formation and antibiotic resistance pattern in extended-spectrum β-lactamase-producing
escherichia coli
strains
p. 175
Nabi Jomehzadeh, Khadijeh Ahmadi, Zahra Nasiri
DOI
:10.4103/bbrj.bbrj_270_21
Background:
The increasing prevalence of multidrug-resistant (MDR)
Escherichia coli
strains, especially extended-spectrum beta-lactamase (ESBL)-producing strains, has become a global health concern. This study was aimed to determine the frequency of
bla
CTX-M
,
bla
TEM
, and
bla
SHV
genes among
E. coli
isolates from urinary tract infection (UTI) and evaluate their antibiotic resistance pattern.
Methods:
Totally 98
E. coli
isolates were recovered from urine samples of UTI-diagnosed patients. Antibiotic resistance and ESBL production were evaluated by disk diffusion and combined disk methods according to the Clinical Laboratory Standards Institute guidelines. The biofilm formation ability of isolates was assessed using the tube adherence method. ESBL-positive isolates were screened for
bla
TEM
,
bla
CTX-M
, and
bla
SHV
genes by polymerase chain reaction.
Results:
Among the examined isolates, 25 (25.5%) were detected as ESBL producers and harbored at least one of the studied genes. The
bla
CTX-M
was the predominant (44%) gene, followed by
bla
TEM
(24%) and
bla
SHV
(8%). The isolates revealed variable resistance levels to all antimicrobials, out of which 55.1% were conferred a high resistance rate to different antibiotic classes and considered MDR. Phenotypically, 42.85% of the isolates were biofilm formers, of which the majority (38%) formed moderate biofilms.
Conclusions:
This study showed that the ESBL-positive isolates were more resistant to some first-line antibiotics, and this highlights the necessity to control and monitor the prescribed antibiotics used for empirical treatment for UTI patients.
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Screening the
in-vitro
Antibacterial Activity of Different Naturally Produced Coal and Coal Mediated Commercial Products on Clinically Isolated Pathogens
p. 180
Shawda Shafiq Shreya, Tamanna Islam, Touhida Ishma, Irin Sultana Polin, Fahim Monwar Nazia, Mrityunjoy Acharjee
DOI
:10.4103/bbrj.bbrj_273_21
Background:
The rise of microbial illnesses caused by drug-resistant microflora is one of the most serious public health concerns, therefore identifying novel antimicrobial agents is crucial in combating multidrug-resistant bacterial strains.
Methods:
Present Investigation designated to assess the microbiological status of some naturally produced coal and coal mediated commercial products collected from Barapukuria Coal Mine Dinajpur and different retailer in Dhaka city, respectively through conventional cultural and biochemical tests. Moreover, the anti-bacterial potential of both categories of coal samples was also aimed to be checked by the agar well diffusion method and minimal inhibitory concentration (MIC) assay.
Results:
Out of 10 samples, total viable bacteria was estimated at high range in all the samples excluding the charcoal. In case of specific bacteria, only
Staphylococcus
spp. was found in both types of samples while
Klebsiella
spp. was found in coal mediated commercial products. Both categories of samples showed their anti-bacterial activity with satisfactory range of zone diameter (9 mm–26 mm). However, the naturally produced coal was unable to show their anti-bacterial activity against
Bacillus
spp.,
Shigella
spp. and
Vibrio
spp. through agar well diffusion methods. Meanwhile, the minimal concentration of all the samples was successfully quantified as MIC value at which the bacterial growth was retarded. In case of naturally produced coal, the lowest concentration 4 mg/ml was recorded for wooden coal powder against
Escherichia coli
while the maximum concentration was estimated at 34 mg/ml. Conversely, the MIC value was varied between 4 mg/ml to 24 mg/ml in case of coal mediated commercial products.
Conclusion:
The results of this study suggest that the naturally produced coal and coal-mediated products have excellent antibacterial characteristics which indicating their economic potential for treating various infectious disorders.
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“Asymptomatic”
plasmodium falciparum
parasitemia and micronutrient deficiencies among pregnant women in Oyo State
p. 185
Mufutau Mosunmade Azeez, Frederick Olusegun Akinbo
DOI
:10.4103/bbrj.bbrj_255_21
Background:
Plasmodium falciparum
parasitemia coupled with nutritional deficiencies, especially relating to micronutrients in pregnancy, may be a recipe for adverse pregnancy outcomes. This study was conducted to determine the prevalence of asymptomatic
P. falciparum
infection and some micronutrient deficiencies among pregnant women in Oyo State.
Methods:
Three hundred and sixteen pregnant women aged 16–45 years and 100 apparently healthy nonpregnant women of the same age range serving as controls from the 3 senatorial districts of Oyo State were enrolled in this study after obtaining their consent. Blood samples were collected and examined for
P. falciparum
using RDT kit and Giemsa-stained film microscopy while the selected micronutrients – calcium, iron, copper, and zinc – were assayed with atomic absorption spectrophotometer.
Results:
P. falciparum
was detected in 82 out of the 316 pregnant women studied representing a percentage prevalence of 25.95 while the prevalence rate was 1% (1 out of 100) among the nonpregnant control women (
P
< 0.0001). Factors that significantly impacted on
P. falciparum
prevalence were pregnancy status, age, gestational age, parity, and seasonal variations. Out of the 316 pregnant women studied, 27 (8.5%) and 35 (11.1%) were deficient in calcium and iron, respectively. However, 13 of the 82 parasitemic pregnant women (15.85%) had calcium micronutrient deficiency, with only 14 out 234 (5.98%) observed in nonparasitemic pregnant women (
P
< 0.0001). While 10 (12.19%) had iron deficiency among the parasitemic pregnant women, 25 (10.68%) had iron deficiency among the nonparasitemic pregnant women. The only parasitemic nonpregnant control out of the 100 had calcium and iron micronutrient deficiencies (100%) as against 24.24% and 20.24%, respectively, in nonparasitemic controls. Copper and zinc micronutrient deficiencies were not observed among the study subjects.
Conclusion:
Continuous health education with emphasis on compliance to dietary instructions and malaria prevention measures, monitoring parasitemic pregnant women till delivery, and including malaria testing in the routine laboratory tests for antenatal care are hereby advocated.
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Antibiotic Susceptibility Profile and Plasmid Analysis of Micro-Organisms Associated with Ocular Infections
p. 193
Valentine Nnachetam Unegbu, Chris Anyamene, Frederick Odibo
DOI
:10.4103/bbrj.bbrj_274_21
Background:
This study was undertaken to determine the antimicrobial susceptibility profile and plasmid analysis of micro-organisms associated with ocular infections.
Methods:
Ocular specimens were collected from 500 patients. Subsequent identification was done based on morphology and biochemical tests. Susceptibility pattern of the isolates was done using the disk diffusion method. The presence of plasmids was determined using the agar gel electrophoresis technique. Plasmid curing was carried out by treating the MAR isolates with sodium dodecyl sulfate at concentration of 10%.
Results:
Conjunctivitis was the most prevalent ocular infection of 105 (39.8%).
S. aureus
was the most prevalent pathogen 63 (23.9%) followed by CoNS 36 (13.6%).
S. aureus
was 100% sensitive to vancomycin and chloramphenicol. CoNS was also 100% sensitive to ciprofloxacin, vancomycin, and chloramphenicol.
K pneumoniae
was 100% sensitive to gentamicin and amoxicillin-clavulanic acid while
N. gonorrhoeae
was 100% sensitive to gentamicin, ciprofloxacin, ceftriaxone, amoxicillin-clavulanic acid, and cefotaxime. The overall MAR bacteria was 38 (16.2%). Plasmid analysis revealed the presence of 1–3 plasmid bands of sizes 6.21–16.22 Kbp from the MAR isolates. Plasmid curing revealed that the gene coding for resistant seen in this study was plasmid mediated.
Conclusions:
The prevalence of ocular infection was high with conjunctivitis being the dominant. The dominant bacteria species were
S. aureus
and CoNS. The overall MAR bacteria proportion was relatively high. The presence of plasmids was responsible for the resistance of the isolates to antibiotics.
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Her2neu Expression of Gastric and Lower Esophageal Carcinoma and its Correlation with Clinicopathological Findings in Tertiary Care Hospital in Eastern India
p. 203
Dipsikha Chakraborty, Sanchita Ghosh, Bhawna Bhutoria Jain, Saurav Kumar Ghosh, Ayandip Nandi
DOI
:10.4103/bbrj.bbrj_295_21
Background:
Gastric carcinomas are the fifth most common cancer worldwide and cause the second most common cancer-related deaths. Human epidermal growth factor receptor 2 (HER-2/Neu)(c-erbB2) protein overexpression in gastric cancer has been correlated to poor outcomes and a more aggressive disease. Targeted therapy against HER-2/Neu has attracted much attention recently. Comprehensive data regarding Her2neu expression in gastric carcinoma in Southeast Asia shows highly variable results and often lacks standardization.
Aim/Objective:
In this study, we study the expression of HER-2/Neu marker in lower esophageal and gastric carcinoma and compare it with various clinicopathological parameters and are known to have prognostic significance.
Methods:
One hundred and fifty cases of gastric/gastroesophageal adenocarcinomas (intestinal type) were included in the study over 2 years, and immunohistochemistry was done to evaluate Her2neu expression. Scoring was done according to the American Society of Clinical Oncology/College of American Pathologists guideline, and the finding was correlated with clinicopathological parameters.
Results:
The age of patients ranged from 41 years to 80 years. Gastric tumors were more common in the age group 61–70 years with mean age of 65.5 years. Gastric tumors are more common in males than females. (M:F = 3.16:1) Most common type of specimen received was partial gastrectomy (38%). Anorexia (46%) and pain abdomen (46%) were the most common presenting symptoms. Gastric tumors were common in tubular subtypes (76%) followed by mucinous subtypes (16%). Most common histopathological grading was moderately differentiated gastric adenocarcinoma (64%). Most gastric tumors were located at antropyloric area of the stomach (42%). The highest frequency of cases presented at an tumor, node, metastasis (TNM) stage that is pT
2
N
2
M
x
(32.3%). Her2neu expression was found to be score 0 in most (62%) cases, only 10% of cancers were positive (3+), 14% were equivocal (2+), and another 14% were 1+ (negative). When we correlated clinicopathological parameters such as age,sex,tumour site,gross appearance,size,depth of invasion,TNM stage,Lymphovascular invasion,perineural invasion etc. with HEr2neu expression; no statistically significant correlation was found.
Conclusion:
Overexpression of HER-2/Neu in gastric carcinoma can help to identify patients with reduced survival and to identify eligible candidates for targeted therapy. A larger sample size and follow-up for a longer period might shed more light on the role of the above markers in gastric carcinoma.
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DNA binding and cleavage study of novel ruthenium (II)-polypyridine-5-(3-pyridyl)-4H-1,2,4-triazole-3-thiol complex on
Escherichia Coli
genomic DNA
p. 208
Santhiya Santhiya, Sheeba Daniel
DOI
:10.4103/bbrj.bbrj_302_21
Background:
Transition metal complexes especially Ruthenium-Polypyridyl complexes interact with multidentate ligands considered as a new therapeutic agent to make the possible DNA probes and conformers due to several interests owing to their potential applications. The aim of the present work is to concentrate on the binding and cleavage activity of [Ru(bpy)
2
(pytrzSH)
2
]
2+
(complex 1) and [Ru(phen)
2
(pytrzSH)
2
]
2+
(complex 2) (bpy = 2,2′-bipyridine, phen = 1,10-phenanthroline, pytrzSH = 5-(3-pyridyl)-4H-1,2,4-triazole-3-thiol) on
Escherichia coli
genomic DNA (gDNA).
Materials and Methods:
DNA binding and cleavage activity is carried out using ultraviolet-Visible spectral technique and Agarose gel electrophoresis method at three different concentrations against the standard genomic DNA isolated from
E. coli
bacteria.
Results:
The changes in the absorbance and wavelength upon incremental addition of the complexes on gDNA clearly depict the binding nature of complexes. The binding constant values for ligand centered and metal to ligand charge transfer transitions obtained from the Benesi Hildebrand plots are found to be 1.560 × 10
4
and 9.586 × 10
4
M
−1
for complex 1 and 3.594 × 10
4
and 9.801 × 10
5
M
−1
for complex 2. The results revealed that complex 2 shows better binding property than complex 1 on
E. coli
gDNA. The extent of DNA cleavage activity of the synthesized complexes on
E. coli
gDNA is determined from the band intensities, complex 2 shows full cleavage in all the three concentrations, whereas complex 1 exhibits full cleavage at 100 μg/mL. The cleaving ability depends on the nature of the ligands present in the complexes.
Conclusion:
The synthesized [Ru(bpy)
2
(pytrzSH)
2
]
2+
(complex 1) and [Ru(phen)
2
(pytrzSH)
2
]
2+
(complex 2) bind with the
E. coli
gDNA through electrostatic and intercalative modes. The [Ru(phen)
2
(pytrzSH)
2
]
2+
complex 2 shows better cleavage activity than [Ru(bpy)
2
(pytrzSH)
2
]
2+
complex 1.
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Characterization of markers of chloroquine resistance in
plasmodium falciparum
among pregnant women in Oyo State: Any hope of chloroquine resistance reversal?
p. 216
Mufutau Mosunmade Azeez, Frederick Olusegun Akinbo
DOI
:10.4103/bbrj.bbrj_3_22
Background:
Chloroquine (CQ) which is one of the 4-aminoquinolines was once the mainstay of malaria treatment before it was officially withdrawn due to widespread resistance to it by
Plasmodium
species. It is one of the cheapest, safest, easily produced antimalarial compounds and has one of the longest half-lives among the antimalarial drugs which are also safe for use in pregnancy. Reversal of CQ resistance back to sensitivity has been documented after a period of withdrawal, and this may be a great relief in achievement of effective antimalarial chemotherapy at a relatively cheaper cost in Nigeria. This study investigated the characterization of markers of CQ resistance in
Plasmodium falciparum
infection among pregnant women in Oyo State following several years of official CQ withdrawal for treatment in Nigeria.
Materials and Methods:
Thick and thin blood films were made from venous blood collected from 316 consenting pregnant women and dispensed into ethylenediaminetetraacetic acid bottles after initial screening with SD Bioline RDT kit. The blood films were processed for malaria microscopy using 10% Giemsa stain. Dry blood spots on Whatman no. 1 filter paper were used for parasite DNA extraction and subsequent detection of CQ resistance markers using restriction fragment length polymorphism.
Results:
Eighty-two out of the 316 samples were positive for
P. falciparum
and subjected to molecular analysis for the detection of
Pfcrt
and
Pfmdr1
mutant genes. Out of the 82 positive cases, 75 and 80 expressed mutant
Pfcrt
and
Pfmdr1
genes, respectively, while 73 expressed both
Pfcrt
and
Pfmdr1
genes.
Conclusion:
The high prevalence of the two major molecular markers of CQ resistance in this study, portends a concern in achieving resurgence of sensitivity after years of official withdrawal, thus official malaria management protocols should be strictly adhered to by ensuring testing before drug use while also avoiding self-medication.
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Comparing pili producing gene (mtp-flp) in susceptible and resistant dormant
Mycobacterium tuberculosis
strains with active clinical isolates
p. 224
Zahra Nasirzadeh, Parissa Farnia, Jamileh Nowroozi, Poopak Farnia, Ali Akbar Velayati
DOI
:10.4103/bbrj.bbrj_326_21
Background:
Pili producing genes in different life cycles of
Mycobacterium tuberculosis
(
M. tuberculosis
) were assessed.
M. tuberculosis
has two life cycles: dormant and active states. We aimed to assess the pili producing genes such as curli pili of
M. tuberculosis
(mtp) encoded by the mtp gene (Rv3312A) and fimbrial low-molecular-weight protein encoded by flp gene (Rv3656c) which were compared and analyzed.
Methods:
Two hundred
M. tuberculosis
isolates were investigated both at active and dormant states for production and expression of pili. The dormant
M. tuberculosis
was achieved by incubation in a sealed tube (modified Wayne method). The susceptibility of
M. tuberculosis
was evaluated on genes, rpob, inh, katg, and gyra by using multiplex polymerase chain reaction (PCR) and single-strand conformational polymorphism methods. The PCR–restriction fragment length polymorphism was used to express pili genes mtp and flp and then the PCR products was digested using restriction enzyme Fnu4HI, XmaI, and MspJI and AciI, TagII, and HaeII, respectively. The transmission electron microscopy was also used to detect pili in different isolates. The result was compared and analyzed using H37RV as a gold standard.
Results:
The mtp and flp PCR products were 263 and 122 bp in the studied strains irrespective of
M. tuberculosis
different life cycles, respectively. The PCR products were analyzed on 8% Polyacrylamide gel electrophoresis (PAGE), and in the 180/200 (20%), producing five fragments of 25,40,45,63,90 bp with the Fun4HI and two fragments of 126,138 bp with the XmaI and uncut with the MspJI for mtp gen were obtained at the dormant and active states of
M. tuberculosis
(
P
< 0.05). Similarly in flp gene producing three fragments of 22,35,65 bp with AciI and two fragments of 35.87 bp with TagII and two fragments of 38.84 bp with HaeII were obtained (P < 0.05). In contrast to genotyping analysis, the electron microscopy examination showed protruding of pili from
M. tuberculosis
, especially in dormant mycobacterium (15/100; 15%), that was multidrug resistance and extensive drug resistance isolates (
P
> 0.05).
Conclusion:
Pili were shown by electron microscopy, although at the gene expression, the insignificant difference was observed at the dormant strains in comparison to active states. Therefore, we may conclude that other genes might be involved in pili production of
M. tuberculosis
that needs further investigation. Although, the resistance phenomena might influence the pili producing gene expression that showed in our results.
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A comparative molecular docking study of crocetin with multiple receptors for the treatment of alzheimer's disease
p. 230
Dhanashree Sharadchandra Kherade, Vrushali Sachin Tambe, Anupa Dnyaneshwar Wagh, Prajakta Bhushan Kothawade
DOI
:10.4103/bbrj.bbrj_6_22
Background:
Crocetin, an active constituent derived from
Crocus sativus L.
and
Gardenia jasminoides
, has shown to have multiple pharmacological activities such as memory booster, anti-oxidants, anti-inflammatory, and neuroprotective actions. Clinical trials on Saffron extract and a preclinical trial of Crocetin for neurodegenerative diseases directs probable use of Crocin in Alzheimer's disease (AD). The Crocin metabolizes into Crocetin after administration. The affinity of Crocetin to different receptor for AD on the basis of molecular docking has not yet been investigated. The present study was aimed to identify the affinity of Crocetin with different receptors involved in Alzheimer's pathogenesis by docking. Autodock Tools (MGL Tools), PYMOL, AutoDock Vina, Discovery studio 2021 client and SwissADME were used. Molecular docking simulation showed significant binding affinity of Crocetin to various receptors. It was found to bind significantly with different receptors like Vitamin D receptor (binding energy-7.9 kcal/mol), Receptor for advanced glycation end products (binding energy-7.5 kcal/mol) and NOD-like receptor pyrin domain-containing-3 (binding energy-7.4 kcal/mol). The results obtained suggest the usefulness of Crocetin in AD.
Context:
In this study, we have investigated the binding affinity of Crocetin on different receptors related to AD by performing molecular docking studies.
Aim:
Determination of binding affinity of Crocetin with different receptors involved in AD.
Settings and Design:
Auto dock vina, Pymol, Discovery studio, Auto dock Tools, Chemsketch, Swiss ADME.
Methods:
Molecular docking.
Results:
The Crocetin was found to have significant binding affinity to different receptors such as Vitamin D receptor (binding energy-7.9 kcal/mol), receptor for advanced glycation end products (binding energy-7.5 kcal/mol), and NOD-like receptor pyrin domain-containing-3 (binding energy-7.4 kcal/mol).
Conclusions:
The present study focuses on docking of Crocetin with different receptors related to the treatment of AD. The Crocetin was found to have a significant binding affinity with different receptors like Vitamin D receptor (binding energy-7.9 kcal/mol), Receptor for advanced glycation end products (binding energy-7.5 kcal/mol), and NOD-like receptor pyrin domain-containing-3 (binding energy-7.9 kcal/mol) while it exhibits moderate binding with receptor-like peroxisome proliferator-activated ϒ receptor (binding energy-7.1 kcal/mol), cannabinoid receptors (binding energy-7.1 kcal/mol) and ryanodine receptor (binding energy-7.0 kcal/mol). It showed the best potential to be developed into an anti-Alzheimer's drug due to its binding with multiple targets. From drug likeliness properties it can be seen that Crocetin can be absorbed by the human body and does not violate the Lipinski rule.
Limitations of Study:
Theoretical predictions are just consultative and have to be carefully verified by
in vivo
experiments.
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Phytochemical and biological studies of
salvia chorasanica
p. 243
Saeed Mollaei, Parina Asgharian
DOI
:10.4103/bbrj.bbrj_59_22
Background:
Salvia chorasanica
is a perennial herb endemic to Iran, which grows wild. Due to the lack of data on
S. chorasanica
, the present work focused on chemical composition, as well as antioxidant and antibacterial properties of essential oil and five extracts from aerial parts of
S. chorasanica
.
Methods:
The analysis of chemical composition was done using gas chromatography (GC), GC–mass spectrometry, and high-performance liquid chromatography–photodiode array. Total phenolic and flavonoid contents and antioxidant activities were determined spectrophotometrically. Furthermore, antibacterial activities were investigated using the disk-diffusion method.
Results:
The essential oil analysis indicated that (-)-spathulenol, (-)-caryophyllene oxide, and (E)-caryophyllene were the major compounds. The extracts analysis indicated that ethyl acetate and methanol extracts had high phenolic compounds, and rosmarinic acid, caffeic acid, and luteolin-7-O-glucoside were identified as main phenolic compounds. The biological results showed that the highest antioxidant activity was obtained in the ethyl acetate extract. n-hexane and dichloromethane extracts were highly active against
Staphylococcus aureus
and
Bacillus pumilus
bacteria.
Conclusions:
It can be concluded that the phytochemical compositions and biological activities of
S. chorasanica
could be changed using different extraction solvents.
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Mobile health: A comparative study of medical and health applications in Iran
p. 249
Lida Fadaizadeh, Mohammad Sanaat, Ebrahim Yousefi, Niloofar Alizadeh
DOI
:10.4103/bbrj.bbrj_31_22
Background:
The use of mobile phones in the field of medicine is rapidly increasing in developed and developing countries. This study aimed to evaluate the performance of the top mobile applications based on superiority from the user's point of view and medical content.
Methods:
Information of each app was recorded in a Google Forms, especially designed for this purpose. The Bazaar App Store, which has two main categories for health: medicine and health and fitness, was used as a source for Persian-language Android applications. The apps of these two domains were installed, and our experts reviewed and rated them in terms of content and technical performance.
Results:
From a total of 3500 applications available in the App Store, 112 apps were selected. Of these, 76.8% were in the field of medicine and 23.2% in the field of health and fitness. The developers of the app consisted of four main groups: (1) nonhealth-care organization, (2) individual app developers, (3) health-care organization, and (4) university or academic research group. The top five major areas of services were: (1) general medical services, (2) addressing medical centers and online appointments, (3) drug information, (4) physical activity and (5) patient follow-up.
Conclusion:
The review of users' scores and comparing it with the scores of specialists showed that although people tend to use telemedicine services, since there is still no formally approved framework for design and scientific content of these applications, most apps operate in the field of general information and services.
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Alpha-pinene preserves human dopaminergic SH-SY5Y cells against 6-hydroxydopamine-induced toxicity through its antioxidant and antiapoptotic properties and gamma-aminobutyric acid type A signaling
p. 255
Mandana Moshrefi, Ali Mohammad Pourrahimi, Mehdi Abbasnejad, Mohammad Hadi Farjoo, Saeed Esmaeili-Mahani
DOI
:10.4103/bbrj.bbrj_51_22
Background:
Parkinson's disease (PD) is one of the most common neurodegenerative disorders which is characterized by progressive loss of dopaminergic neurons in substantia nigra. Therefore, drugs or natural agents that have suppressive effects on dopaminergic cell death may reduce the progression of such disorder. Here, the effect of natural product alpha-pinene was evaluated on 6-hydroxydopamine (6-OHDA)-induced damage in SH-SY5Y human dopaminergic cell line as an
in vitro
model of PD.
Methods:
The cells were incubated by 150 μM 6-OHDA alone or accompanied with different concentration of alpha-pinene (10–180 μM). Cell viability was determined by MTT assay. The amount of intracellular reactive oxygen species (ROS) and mitochondrial membrane potential were measured by fluorescence spectrophotometry. In addition, the components of molecular apoptotic pathway such as cytochrome c release, Bax, Bcl-2, and caspase-3 levels were measured by immunoblotting. Gamma-aminobutyric acid (GABA) antagonist, bicuculline, was used to find the role of GABA Type A (GABAA) receptors in the signaling of alpha-pinene.
Results:
The data showed that 6-OHDA produced cell damage, decreased mitochondrial membrane potential, increased intracellular ROS and cytochrome c release, as well as increased Bax/Bcl-2 ratio and caspase-3 activity. Moreover, alpha-pinene (70 μM) significantly inhibited cellular and molecular abnormalities. Blockage of GABAA receptor significantly suppressed the protective effect of alpha-pinene.
Conclusion:
The results suggest that alpha-pinene has a protective effect against dopaminergic toxicity, and at least in part, its antioxidant and antiapoptotic properties are probably involved in such protection.
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Evaluation of mobile phone-based tele-monitoring of cystic fibrosis patients during the COVID-19 pandemic: A 3-year experience in Iran
p. 261
Lida Fadaizadeh, Maryam Hassanzad, Ali Valinejadi, Seyed Mohammad Jafar Taheri, Poopak Farnia, Nima Hassanzad, Hossein Ali Ghaffaripoor, Noushin Baghaei, Mahdieh Arian, Masoumeh Ansari, Zahra Daneshmandi, Elham Sadat Sadati, Parisa Honarpisheh, Mahsa Rekabi, Leila Mohammadpour, Ali Akbar Velayati
DOI
:10.4103/bbrj.bbrj_60_22
Background:
Telemedicine has been used for cystic fibrosis (CF) in a wide range of signs and symptoms even before the COVID 19 pandemic, however, little is known about the health consequences and use of specific health care for cystic CF. This study aimed to evaluate the evolution of clinical trends and data related to mobile based monitoring activities in CF patients at home for 3 years.
Methods:
This is a semi experimental single group study. Forty five CF patients under 7 years' old who were referred to the Masih Daneshvari Hospital between 2018 and 2021 were selected. A mobile phone_based customized Short Message Service (SMS) application used to monitor patients. Remotely monitored variables included the amount and color of sputum, cough, wheezing, and shortness of breath at rest. SPSS using Chi square and Friedman tests.
Results:
The condition of patients based on the number and type of cough increased sputum, decreased appetite, fatty stool, fever and dyspnea, headache, noninvasive ventilation, and drug comfortably remained almost unchanged in the study of the 1st, 2nd, and 3rd years, and the studied parameters did not show a significant difference (P > 0.05). Of course, the number of outpatient visits decreased significantly (P value: 0.02). The respiratory rate and arterial oxygen saturation variables were almost the same in three consecutive annual measurements (P values: 0.544 and 0.639, respectively).
Conclusion:
Telemedicine is a method that is useful in the follow up of chronic diseases such as CF and improves the quality of life and reduces the deterioration of lung function; therefore, there is less need for invasive treatments in the long run, and a fundamental change in referral motivation brings to the hospital.
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Integrated proteomic, transcriptomic, and genomic analysis identifies fibrinogen beta and fibrinogen gamma as key modulators of breast cancer progression and metastasis
p. 266
Hemantkumar Patadia, Ankita Priyadarshini, Ajit Gangawane
DOI
:10.4103/bbrj.bbrj_61_22
Background:
As per the WHO, more than 2 million new cases are diagnosed with breast cancer and more than 685,000 deaths have been reported in 2020. Incidence of recurrence and metastasis has also risen and poses a challenge for developing new therapies with the identification of newer targets.
Methods:
The objective of this study is to analyze and integrate various data across genomic, transcriptomic, and proteomic levels to find promising markers linked with tumor progression and metastasis development in breast cancer. This study begins with the extraction of data of differentially expressed proteins and subsequently analyzes their gene expression changes and genomic alterations to integrate all three omics data. We used curated breast cancer datasets of different proteomic experiments from dbDEPC3.0 and TCGA datasets of the Metastatic Breast Cancer Project to compare gene expressions and genomic alterations. We further used cBioportal, GeneMania, GEPIA2, Reactome, and canSAR computational tools for identifying the most significant genes associated with tumor progression and metastasis.
Results:
Based on false discovery rate, 14 genes were subjected to pathway analysis in Reactome and the top 25 significant pathways were analyzed out of a total of 170 pathways. Our study found fibrinogen gamma (FGG) and fibrinogen beta (FGB) linked to pathways connecting RAS-MAPK, its downstream mutants, integrin signaling, and extracellular matrix remodeling pathways.
Conclusion:
Survival analysis suggested that FGG (
P
= 0.0065) and FGB (
P
= 0.013) have a significant positive correlation along with their stage-wise changes in copy number variations and genomic alterations play a pivotal role in controlling tumor progression and metastasis.
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Detection, clinical features, and laboratory markers of
H.pylori
infection in individuals attended kosti teaching hospital, Sudan
p. 278
Mohammed Eltoum Azoz, Babiker Saad Almugadam, Omer Mohammed Ali Ibrahim, Yousif Mousa Alobaid Ahmed, Amna Ahmed Al Tayeb, Noor Hussin Eshagg, Roaa Azhari Hassan
DOI
:10.4103/bbrj.bbrj_71_22
Background:
Helicobacter pylori
infections are associated with significant morbidity. The study intended to screen
H. pylori
among symptomatic patients and assess the performance of anti-
H. pylori
immunoglobulin G (IgG) test compared to stool Ag test as well as to investigate some clinical and hematology findings in
H. pylori
-seropositive persons.
Methods:
One hundred individuals with the clinical suspicion of infection by
H. pylori
and 100 control subjects matched for gender (
χ
2
= 0.026,
P
= 0.873) and age groups (
χ
2
= 5.303,
P
= 0.151) were recruited. Clinical assessment, endoscopy, anti-
H. pylori
IgG test, and stool for cagA Ag were performed to investigate
H. pylori
infection. White blood cells, red blood cells (RBCs), hemoglobin (Hb), and mean corpuscular hemoglobin (MCH) were also analyzed.
Results:
Vomiting and hematemesis were reported in 44% and 8% of the study group, respectively. Whereas, nausea, epigastric pain, and weight loss were observed in all (100%). Notably, gastritis and duodenal ulcer were detected in 100% and 80% of cases, respectively. Based on Immunochromatographic test (ICT), 75% and 78% of the study group were positive for anti-
H. pylori
Ab and cagA Ag of
H. pylori
, respectively. The odd of reported a positive result for
H. pylori
was less likely in females than males as determined by anti-
H. pylori
(odds ratio [OR]: 0.529, 95% confidence interval [CI]: 0.142–1.970,
P
: 0.343) and stool cagA Ag test (OR: 0.364, 95% CI: 0.087–1.532,
P
: 0.168). Compared to the cagA Ag test, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of anti-
H. pylori
test were 77.2%, 85.3%, 78.7%, 84.1%, and 81.9%, respectively. Interestingly, RBCs count, MCH, and Hb were significantly higher in the control compared to study cases,
P
< 0.05.
Conclusions:
Our results highlight the epidemiology of
into H. pylori
, assess the performance of anti
H. pylori
test compared to cagA Ag test, and demonstrate the direct link between some hematologic indices and
H. pylori.
Further studies are necessary to verify these findings.
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Biological implications of deletion p53 by fluorescence
in situ
hybridization in multiple myeloma
p. 284
Vijith Vittal Shetty, Meenakshi Arumugam, Reshma Arun Shetty, Akanksha Ashok Kalal, Nagaraj Venkatesh Kulkarni, Deyyenthody Prashanth Shetty
DOI
:10.4103/bbrj.bbrj_84_22
Background:
Multiple myeloma (MM) is a clonal plasma cell disorder characterized by heterogeneous complex genetic abnormalities. Due to the low proliferative index of plasma cells, conventional cytogenetic (CC) analysis is hampered in MM. Interphase fluorescence
in situ
hybridization (FISH) along with CC enhances the sensitivity of detection. The study aims to investigate the diagnostic yield and prevalence of P53 deletion in patients with MM.
Materials and Methods:
Cytogenetic analysis and FISH were performed on 41 MM patients.
Results:
Our study showed that 55–65 years of age range among all individuals, predominantly affected by the disease. The cytogenetic analysis detected abnormal karyotype in 12% (5/41), normal karyotype in 66% (27/41), and culture failure in 22% (9/41). Abnormal karyotype showed numerical abnormalities such as hyperdiploidy 5% (
n
= 2) and hypodiploidy 7% (
n
= 3%). Chromosomes 5, 9, 11, and 21 were common gains among hyperdiploid cases. Chromosome 7, 17, 22 and Y were the common missing chromosome in hypodiploid cases. P53 gene deletion is a rare genetic event and difficult to identify using CC. FISH analysis of deletion 17p was detected in 15% (6/41). Out of six cases, two cases showed deletion of 17p region, three cases showed monosomy 17, and one case showed amplification signals for chromosome 17. Conclusion: CC along with FISH increases the rate of detection of abnormality in MM cases. P53 being less frequent is uncommon at initial diagnosis; increasing its incidence with advanced stage is considered one of the important prognostic factors in MM.
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Comparison of microalbuminuria, creatinine, and glomerular filtration rate between sickle cell disease patients and healthy individuals
p. 289
Abazar Mahmoud Ismail, Adam Dawoud Abakar, Mubarak Elsaeed Mustafa Elkarsany, Babiker Saad Almugadam
DOI
:10.4103/bbrj.bbrj_67_22
Background:
Sickle cell disease is related to many health issues (such as stroke, severe infections, and sickle cell crisis) and elevated risk of death. This study was aimed to investigate and compare microalbuminuria (MAU), creatinine, and glomerular filtration rate (GFR) between sickle cell disease (SCD) patients and healthy individuals.
Methods:
A total of 156 cases and 156 control subjects were included. MAU, creatinine, GFR, and body mass index (BMI) were measured.
Results:
The estimated levels of MAU and creatinine were significantly higher in cases than controls, but the mean of BMI and GFR was significantly lower in cases than the control group. In patients of sickle cell disease, the mean MAU, GFR, creatinine, and BMI levels in females, rural area residents, and subjects aged 2–13 years were higher than controls,
P
< 0.05. MAU and GFR were also higher (
P
< 0.05) in males and subjects aged 14–25 years of study cases than controls.
Conclusion:
Accordingly, this study indicated the impact of SCD in MAU, creatinine, GFR, and BMI, which are significant in the diagnosis of nephropathy.
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