ABSTRACT
Aim/Introduction: Inoperable HCC patients with multifocal lesions and malignant portal vein thrombosis (PVT) have poorer prognosis with limited treatment options. 188Re-N-DEDC lipiodol is an emerging agent for such cases due to its simple and on-site labelling procedure, cost-effectiveness and least radiation induced side effects. We aimed to explore the response assessment, safety and efficacy of 188Re-N-DEDC-lipiodol in multifocal HCC with/without PVT. Material(s) and Method(s): Radiologically and biochemically confirmed HCC patients with/without PVT having ECOG performance status <=2 and Child Pugh score A /B were recruited. Baseline serum alpha-fetoprotein (AFP) was obtained for biochemical correlation and follow-up. After lipiodol labelling & QC checks, therapeutic activity of 188Re-N-DEDC/lipiodol were injected under fluoroscopic guidance through femoral branch in super-selective artery of tumor. Post-therapy planar and SPECT/CT imaging were performed at 2, 6, 12, 24, 48 and 72hrs to see tumoral retension. Response was assessed at 2 months post-therapy by mRECIST criteria and S. AFP level. Clinical & biochemical toxicities were graded by CTCAE v5.0. Result(s): Thirty-One (31) patients (27 male;4 female) with mean age 55.9 +/- 9.78 years have been recruited for therapy. Overall mean injected activity of 188Re-N-DEDC lipiodol was 2.9+/-0.9GBq (78.4+/-24.2mCi). The median follow-up period was of 6 months. One patient was lost to follow-up due to prevailing COVID situations and 3 patient died before follow-up due to internal variceal bleeding, so radiological and biochemical response were assessed only in 27/31 patients by mRECIST criteria and serum AFP tumor marker level respectively. Radiologically, objective response rate was seen in 12/27 patients (~45%) and disease control rate was seen in 20/27 patients (~74%). 6/27 patients had non-AFP producing tumor i.e. serum AFP were normal at baseline and follow-ups while in remaining 21 patients, biochemical objective response rate was seen in 11/21 patients (~52%) and disease control rate was 14/21 patients (~67%). Post-therapy clinical toxicities (Nausea, Vomiting, Fever, abdominal pain) were observed in most of the patients for 2-3 days and were treated symptomatically. One patient showed grade 3 liver toxicity & progressive worsening of LFT, 20 patients showed grade 1 derangements in liver enzymes & 6 patients showed grade 2 derangements in liver enzymes. Hematological toxicities were seen in 4 patients (<=Grade 2 in 2 patients & grade 3 in two patients). Conclusion(s): In patients of HCC with/without PVT, trans-arterial Re188-N-DEDC/lipiodol therapy proved to be safe and effective with good disease control.
ABSTRACT
Background: Glycyrrhiza uralensis, also known as liquorice, is a herbal remedy that is traditionally used worldwide for treating respiratory ailments and ameliorating breathing. Objective: The objective of this systematic study was to investigate active ingredients of Glycyrrhiza uralensis and determine its mode of action in silico against severe and acute respiratory complications of respiratory ailments through network pharmacology and molecular docking studies. Methods: TCMSP database search helped retrieve the compounds of Glycyrrhiza uralensis and their protein targets, especially related to respiratory ailments. Subsequently, the protein-protein association was attained as a network by using the STITCH database. Cytoscape and its ClueGO plugin were used to study gene ontology (GO) enrichment. In addition, seven natural compounds were docked in the active site of four different molecular targets;JUN-FOS, COX2, MAPK14 and IL-6, to identify the binding mechanism of ligands under study. Results: TCMSP database search resulted in the retrieval of 280 compounds of Glycyrrhiza uralensis (including formononetin, naringenin, sitosterol, isorhamnetin, kaempferol, quercetin and Glycyrrhizin) and 135 protein targets. A careful study of targets showed that 26 prospective targets (including JUN, FOS, IL6, MAPK14 and PTGS2) related to respiratory ailments were identified. Gene ontology (GO) enrichment analysis resulted in the retrieval of 176 GO terms, which were associated with respiratory ailments. This study proposed that Glycyrrhiza uralensis acts against respiratory ailments through various proteins, such as JUN, FOS, IL6, MAPK14 and PTGS2. Docking results revealed that among all studied ligands, the flavonoid-based compounds isorhamnetin and kaempferol form stronger complexes with JUN-FOS-DNA, MAPK-14, and IL-6 proteins (Cscore=6.81, 4.27, and 4.77, respectively) and the saponin based compound glycyrrhizin (Cscore=13.07) demonstrated stronger binding affinity towards COX2 enzyme. Conclusion: Conclusively, isorhamnetin, kaempferol and glycyrrhizin in Glycyrrhiza uralensis may regulate several signaling pathways through JUN-FOS-DNA, MAPK-14, and IL-6, which might play a therapeutic role against respiratory ailments.
ABSTRACT
The COVID-19 pandemic has badly affected the human health and exerted a negative impact on national and global economies. The understanding, observations and responses of the general public during COVID pandemic may help in discussion about healthiness risk and encourage acquiescence with standard guiding principles. Therefore, the study was aimed to measure the Knowledge, Attitude and Practice (KAP) of an individual regarding the COVID-19. However, the present learning was in the setting of a web based cross sectional study conducted to evaluate the KAP among the general public via the dissemination of online Performa. In this context, a questionnaire was designed that was comprised into various scoring divisions to calculate the KAP. The KAP response was achieved from 842 persons and of this strength, 344 were male and 498 responses were attained from females. The Percentages and the frequencies were reported and calculated for each of the response and the chi-square test was applied to find the association (considering pvalue >0.05 as significant). The questionnaire was executed to the age of 22 years and above. On the basis of revealed knowledge (K1-7), the result of K3 and K7 were found highly significant (p-0.001), whilst the K4 response was significant (P≥0.05). The rest Ks were reported non-significant. Likewise, attitude (A1-5) was reported with high percentage in females and overall it was revealed highly significant (p- 0.002) in A5 response. In general, attitudes among genders were found comparatively encouraging and meaningful. Moreover, practices (P1-4) regarding COVID-19 showed week response to the sub divisions of P1-4 but, P2 and P3 were showed highly significant i.e. p-0.00 in both cases. Hence, majority of the general public presented good response against KAP regarding the COVID-19 pandemic. Additionally, incorporation of good practices and knowledge in life can enhance and maintain the population health. In this respect, the policymakers of government organizations have performed well in pointing the grass root populations having no education and un-aware workers via health promotional activities. © 2022
ABSTRACT
Background: Unani System of Medicine (USM) is one of the traditional systems of medicine practiced in India and the Indian subcontinent. It is a holistic system of health care based on inceptive principles applied by Hippocrates, Galen, and Ibn-e-Sina, the founders of present-day medicine. USM encompasses a distinct way of looking at the human body and it considers health to be the result of natural dynamic harmonious balance within the body. USM also recognizes the presence of inherent wisdom which is responsible for controlling all physiological functions, maintenance of health, restoration of health, and self-healing. This intrinsic ability of the body to restore health and the mechanism that activates the body's healing process is called Tabi'at/ physis. The ultimate goal of prevention of disease can be obtained by optimization of tabi'at/physis, increasing the host defense. It can be achieved through the implication of asbab-e-sitta zarooriyah which includes some Unani Regimenal Therapies also, fostering change in lifestyle habits resulting in good health. Aims: In this raging pandemic all the therapeutic strategies are based on destroying the agent, breaking the means of transmission and immunization. Although we are leaving behind a huge gap in maintaining the host defense even though it has a crucial role in disease dynamics. In this paper, we have attempted to highlight the concept of tabi'at/Physis and its optimization to prevent this disease and its transmission.
ABSTRACT
The pandemic Coronavirus (Covid-19) is continuously growing and spreading at the highest rate in all over the world. So, it is necessary to produce the new medicinal agents against this virus. The aim of the present study is to design a potent compound against COVID-19. Based on 3C-like main protease and recently developed solved structure (PDB ID: 6Y2F), a series of remdesivir analogs are designed and analyzed by employing molecular modeling against the SARS-CoV-2 by insilico approach. The molecular dynamics (MD) simulation for 500ps was performed to check the stability and orientation to inside the binding pocket for analogs R3, R9, R14 and R15. The study results exhibit that compsound R9 has strong interaction or least binding energy (-10.04kcal/mol) as compare to the other analogues due to the presences of methyl bromide and it may be useful to further investigation in vitro testing against Covid-19.