Nonsynonymous mutations in VEGF receptor binding domain alter the efficacy of bevacizumab treatment.

Vascular endothelial growth factor (VEGF) mediated angiogenesis is crucial for tumor progression. Isoforms of VEGF bind to different VEGF receptors (VEGFRs) to initiate angiogenesis specific cellular signaling. Inhibitors that target both the receptors and ligands are in clinical use to impede angiogenesis. Bevacizumab, a monoclonal antibody (mAb) approved by the Food and Drug Administration (FDA), binds in the VEGF receptor binding domain (RBD) of all soluble isoforms of VEGF and inhibits the VEGF-VEGFR interaction. Bevacizumab is also used in combination with other chemotherapeutic agents for a better therapeutic outcome. Understanding the intricate polymorphic character of VEGFA gene and the influence of missense or nonsynonymous mutations in the form of nonsynonymous polymorphisms (nsSNPs) on RBD of VEGF may aid in increasing the efficacy of this drug. This study has identified 18 potential nsSNPs in VEGFA gene that affect the VEGF RBD structure and alter its binding pattern to bevacizumab. The mutated RBDs, modeled using trRosetta, in addition to the changed pattern of secondary structure, post translational modification and stability compared to the wild type, have shown contrasting binding affinity and molecular interaction pattern with bevacizumab. Molecular docking analysis by ClusPro and visualization using PyMol and PDBsum tools have detected 17 nsSNPs with decreased binding affinity to bevacizumab and therefore may impact the treatment efficacy. Whereas VEGF RBD expressed due to rs1267535717 (R229H) nsSNP of VEGFA has increased affinity to the mAb. This study suggests that genetic characterization of VEGFA before bevacizumab mediated cancer treatment is essential in predicting the appropriate efficacy of the drug, as the treatment efficiency may vary at individual level.

Perspectives on reforming the tobacco tax administration system in Bangladesh to enhance public health.

BACKGROUND: Taxation is the most cost-effective instrument to regulate the consumption of tobacco products. However, weak tax administration can compromise the effectiveness of taxation. This paper aimed to understand the process of the current tobacco tax administration system in Bangladesh, identify gaps and outline the policy priorities to strengthen the tobacco tax administration process in Bangladesh. METHODS: A sequential qualitative study was conducted in two linked phases: (a) document review and evidence synthesis; and (b) 20 key informant interviews and one workshop with relevant stakeholders to validate the findings generated from both phases. RESULTS: The complex tax system combined with weak tax administration leads to tax evasion in Bangladesh. The processes of procuring and collecting banderoles and tax stamps vary between cigarette and biri companies, and across large and small tax-paying companies. The use of banderoles at the factory level is maintained manually, and there is no system to routinely verify the authenticity of banderoles. Many unregistered small-scale tobacco manufacturing units often reuse the banderoles on new packs. Shortage of staff with inadequate training at the National Board of Revenue restricts adequate tobacco market monitoring. Electronic tax stamps and banderoles combined with a secure digital tracking and tracing system should be introduced to better monitor the supply, distribution and sale of tobacco products. Training needs to be provided to develop capacity of relevant officials. CONCLUSION: The tobacco tax administration needs to be strengthened to increase the government's tobacco tax revenue and protect public health.

True brachial artery aneurysm: A systematic review.

Objective: To identify and critically appraise literature on true brachial artery aneurysm, exploring its demographic characteristics, aetiologies, clinical manifestations and different methods of repair along with complication rates to determine future treatment strategies. METHODS: The systematic review was conducted at Liaquat National Hospital, Karachi, from September 30, 2021, to November 30, 2022, in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Literature was searched on MEDLINE, EMBASE and Cochrane databases for relevant studies in English language or with English translation published till May 31, 2022. The key words used for the search were "brachial artery aneurysm". Data was noted on a proforma and was subjected to descriptive analysis. RESULTS: Of 113 articles, 6 (5.3%) were retrospective studies, 7 (6.1%) were case series and 100 (88.4%) were case reports. The total number of patients involved was 157 with mean age 43.1±23.4 years (range: 2 months to 84 years). The gender was mentioned for 152(96.8%) patients; 111(73%) males and 41(27%) females. The mean diameter of true brachial artery aneurysm was 36.2 ±17.5mm and 106(67.5%) patients presented with localised swelling, 65(41.4%) with pain, 41(26.1%) with distal ischaemic symptoms, and 28(17.8%) with median nerve compression. True brachial artery aneurysms were more common in renal failure patients having a history of arteriovenous fistula creation in the affected limb and were on immunosuppressant drugs due to renal transplant 81(51.5%). Less common causes included primary/idiopathic 27(17.1%), trauma 13(8.2%), connective tissue disorders 8(5%) and vasculitis 7(4.5%). The treatment of choice was aneurysmectomy in 142(90.4%) cases, with revascularisation of limb primarily with reversed great saphenous vein graft 79(50.3 %), followed by end-to-end anastomosis of brachial artery 17(10.8%) and synthetic grafting 17(10.8%). Endovascular intervention was performed in 6(3.8%) cases to exclude true brachial artery aneurysm, and to re-establish adequate blood flow to the associated limb. Conclusion: True brachial artery aneurysm, although a rarity, may lead to significant neurological and vascular problems if ignored. Arteriovenous fistula and immunosuppression are identified as two significant risk factors in the development of true brachial artery aneurysm. Therefore, an effective long-term follow up in renal failure patients is recommended to prevent its complications. Open surgical repair has been the most preferred mode of treatment, but further significant studies are needed to explore and compare different modes of surgical intervention, like open versus endovascular, to plan future treatment strategies.

Effects of beetroot (Beta vulgaris) supplements on selective enzymatic and non-enzymatic antioxidants in iron deficiency anemia.

Iron deficiency anemia (IDA) is not only associated with iron deficiency but has shown strong association with the over production of free radicles and deficiency of antioxidant enzymes. The result of this imbalance is oxidative stress (OS) which is now considered as an important associated factor with various diseases. Treating IDA in most of cases with oral iron supplements results in more OS as iron is a transition metal. A more suitable alternate for iron supplementation is Beta vulgaris supplement, which being herbal in origin is far less associated with side effects. We studied effects of beta vulgaris supplements on enzymatic and non-enzymatic antioxidants in IDA patients. A significant increase in all study parameters were observed after treatment (p <0.05). When pre-supplemental values of super oxide dismutase (SOD) and reduced glutathione (GSH-PX) of IDA were compared with post-supplemental values, they were significantly low (p <0.05). A positive correlation was noted between the two antioxidants and hemoglobin (Hb) values suggesting a direct relationship between antioxidant status and Hb levels. Non enzymatic antioxidants included vitamin A,C and E. We also found a significant improvement (p <0.05) of these vitamins when compared with their initial values and the control group. Our study shows improvement of antioxidant status of anemic patients with 12 week supplementation of Beta vulgaris.

Evaluating the transmission feasibility of SARS-CoV-2 Omicron (B.1.1.529) variant to 143 mammalian hosts: insights from S protein RBD and host ACE2 interaction studies.

In comparison to previously known severe respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, the newly emerged Omicron (B.1.1.529) variant shows higher infectivity in humans. Exceptionally high infectivity of this variant raises concern of its possible transmission via other intermediate hosts. The SARS-CoV-2 infectivity is established via the association of spike (S) protein receptor binding domain (RBD) with host angiotensin I converting enzyme 2 (hACE2) receptor. In the course of this study, we investigated the interaction between Omicron S protein RBD with the ACE2 receptor of 143 mammalian hosts including human by protein-protein interaction analysis. The goal of this study was to forecast the likelihood that the virus may infect other mammalian species that coexist with or are close to humans in the household, rural, agricultural, or zoological environments. The Omicron RBD was found to interact with higher binding affinity with the ACE2 receptor of 122 mammalian hosts via different amino acid residues from the human ACE2 (hACE2). The rat (Rattus rattus) ACE2 was found to show the strongest interaction with Omicron RBD with a binding affinity of -1393.6 kcal/mol. These distinct strong binding affinity of RBD of Omicron with host ACE2 indicates a greater potential of new host transmissibility and infection via intermediate hosts. Though expected but the phylogenetic position of the mammalian species may not dictate the Omicron RBD binding to the host ACE2 receptor suggesting an involvement of multiple factors in guiding host divergence of the variant.

The effects of age, origin, and biological sex on rodent mast cell (BMMC and MC/9) and basophil (RBL-2H3) phenotype and function.

Mast cells initiate allergic inflammatory immune responses and play a role in disease by releasing various inflammatory and immunomodulatory mediators. Several mast cell-lines and primary cultured cells have been used as mast cell models with inconsistent results among research groups. Bone marrow-derived mast cells (BMMC) cultured from mouse bone marrow progenitor cells are often used as a representative model of mucosal mast cell behaviour, however their reported phenotype is variable due to inconsistent culture protocols. RBL-2H3 is a rat basophilic histamine-releasing cell line that has some characteristics of both mast cells and basophils but is not a true representation of either cell type. The murine mast cell line MC/9 is an IL-3-dependent mucosal mast cell model but has limited mast cell characteristics. In this study, we have compared the response of BMMC (derived from C57BL/6 male or female mice), two sources of RBL-2H3 (purchased directly from ATCC and a lab curated culture), and MC/9 (ATCC) at several critical stages to some common stimuli (IgE/Ag, A23187) and analyzed mast cell morphology, expression level of common mast cell surface markers (CD117 and FcεRI), protease expression, and function (growth kinetics, viability, ROS production, degranulation, cytokine release and FcεRI signaling). The objective of this study was to provide insight into the effects of culture conditions, biological sex, and age of the cells on variability among reported phenotypes and, to determine optimal conditions for activation of these cells. Our data show that factors that are often overlooked such as source, age and biological sex of mast cells play an integral role in phenotypic outcomes and may account for the reported variability in their function.

Facile extraction of berberine from different plants, separation, and identification by thin-layer chromatography, high-performance liquid chromatography, and biological evaluation against Leishmaniosis.

The extraction of berberine was carried out from Berberis vulgaris, Berberis aquifolium, and Hydrastis canadensis plants using ethanol and water (70:30, v/v). The extracted berberine was characterized by ultraviolet-visible and Fourier-transform infrared spectroscopy. The purity of berberine was ascertained by thin-layer chromatography using n-propanol-formic acid-water (95:1:4) and (90:1:9) solvents. hRf values were in the range of 44-49 with compact spots (diameter 0.2-0.4 cm). HPLC was carried out using ammonium acetate buffer and acetonitrile in gradient mode with Zodiac (4.6 × 150 mm, 3 µm) column. The flow rate was 1.0 mL/min and detection was at 220 nm. The values of separation and resolution factors of the standard and the extracted berberine were in the range of 1.13-1.16 and 1.40-1.71, respectively. A comparison has shown that both thin-layer chromatography and high-performance liquid chromatography (HPLC) methods found applications in different situations and requirements. The extracted berberine samples were used to treat Leishmaniosis and the results showed better activity of berberine in comparison to the standard drug Amphotericin B. Briefly, the reported research is a novel and may be used to extract berberine from plants, separation and identification of berberine by thin layer chromatography and HPLC and to treat Leishmaniosis.

RF-Enabled Deep-Learning-Assisted Drone Detection and Identification: An End-to-End Approach.

The security and privacy risks posed by unmanned aerial vehicles (UAVs) have become a significant cause of concern in today's society. Due to technological advancement, these devices are becoming progressively inexpensive, which makes them convenient for many different applications. The massive number of UAVs is making it difficult to manage and monitor them in restricted areas. In addition, other signals using the same frequency range make it more challenging to identify UAV signals. In these circumstances, an intelligent system to detect and identify UAVs is a necessity. Most of the previous studies on UAV identification relied on various feature-extraction techniques, which are computationally expensive. Therefore, this article proposes an end-to-end deep-learning-based model to detect and identify UAVs based on their radio frequency (RF) signature. Unlike existing studies, multiscale feature-extraction techniques without manual intervention are utilized to extract enriched features that assist the model in achieving good generalization capability of the signal and making decisions with lower computational time. Additionally, residual blocks are utilized to learn complex representations, as well as to overcome vanishing gradient problems during training. The detection and identification tasks are performed in the presence of Bluetooth and WIFI signals, which are two signals from the same frequency band. For the identification task, the model is evaluated for specific devices, as well as for the signature of the particular manufacturers. The performance of the model is evaluated across various different signal-to-noise ratios (SNR). Furthermore, the findings are compared to the results of previous work. The proposed model yields an overall accuracy, precision, sensitivity, and F1-score of 97.53%, 98.06%, 98.00%, and 98.00%, respectively, for RF signal detection from 0 dB to 30 dB SNR in the CardRF dataset. The proposed model demonstrates an inference time of 0.37 ms (milliseconds) for RF signal detection, which is a substantial improvement over existing work. Therefore, the proposed end-to-end deep-learning-based method outperforms the existing work in terms of performance and time complexity. Based on the outcomes illustrated in the paper, the proposed model can be used in surveillance systems for real-time UAV detection and identification.

Curcumin and Plumbagin Synergistically Target the PI3K/Akt/mTOR Pathway: A Prospective Role in Cancer Treatment.

Cancer development is associated with the deregulation of various cell signaling pathways brought on by certain genetic and epigenetic alterations. Therefore, novel therapeutic strategies have been developed to target those pathways. The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) (PI3K/Akt/mTOR) pathway is one major deregulated pathway in various types of cancer. Several anticancer drug candidates are currently being investigated in preclinical and/or clinical studies to target this pathway. Natural bioactive compounds provide an excellent source for anticancer drug development. Curcumin and plumbagin are two potential anticancer compounds that have been shown to target the PI3K/Akt/mTOR pathway individually. However, their combinatorial effect on cancer cells is still unknown. This study aims to investigate the synergistic effect of these two compounds on the PI3K/Akt/mTOR pathway by employing a sequential molecular docking and molecular dynamics (MD) analysis. An increase in binding affinity and a decrease in inhibition constant have been observed when curcumin and plumbagin were subjected to sequential docking against the key proteins PI3K, Akt, and mTOR. The MD simulations and molecular mechanics combined with generalized Born surface area (MM-GBSA) analyses validated the target proteins' more stable conformation when interacting with the curcumin and plumbagin combination. This indicates the synergistic role of curcumin and plumbagin against cancer cells and the possible dose advantage when used in combination. The findings of this study pave the way for further investigation of their combinatorial effect on cancer cells in vitro and in vivo models.

Treatment of superior mesenteric artery mycotic aneurysm by synthetic vascular graft: A case report.

Superior mesenteric artery (SMA) aneurysm is a rare disease, especially if it is mycotic (infective) in origin. It is difficult to detect the problem during its initial natural course and usually presents in late phase due to its complications such as rupture, dissection, haemorrhage, and mesenteric ischaemia. Initially, the patient present with non-specific symptoms like vague colicky abdominal pain, nausea, vomiting, discomfort, malaise, and low-grade fever but prompt workup and intervention can lead to definitive diagnosis and uneventful outcome. This report describes the case of a 60-year-old male patient who presented with non-specific abdominal symptoms and, on workup, was diagnosed with superior mesenteric artery mycotic aneurysm. It was successfully treated surgically by resection of aneurysm and reconstruction of superior mesenteric artery by inter-positional Polytetrafluoroethylene (PTFE) synthetic vascular graft.

Effect of prior radiation on stage, differentiation, and survival in bladder cancer.

PURPOSE: Clinically significant differences in radiation-related bladder tumors are not well-characterized, and survival analyses are needed. In this study, we aimed to utilize a national cancer database to evaluate the effect of prior radiation on tumor characteristics and survival in bladder cancer patients. METHODS: The Surveillance, Epidemiology, and End Results (SEER) 9 database was queried to identify patients diagnosed with bladder cancer as a second malignancy. Patients having undergone radiation prior to developing bladder cancer were selected for comparative analysis. Logistic regression was used to generate odds ratios to evaluate differences in differentiation, stage, grade, and tumor size. Kaplan-Meier analysis and Cox non-proportional hazards regression models were used to assess the association between previous radiation and bladder cancer survival. RESULTS: A total of 25,408 patients were identified, of which 14,570 patients had sufficient data for analysis. Of these, 5968 (41.0%) received radiation for their primary malignancy. Prior radiation conferred a lower risk of developing moderately- or poorly-differentiated bladder tumors and muscle invasive or node-positive disease. An increased risk of squamous cell carcinoma was noted (OR 1.43, CI 1.06-1.93). Prior radiation led to an increased risk of bladder cancer-specific (HR 1.13, CI 1.03-1.24) mortality at 5 years. The greatest effect of prior radiation was an increased risk of bladder cancer-specific mortality for carcinoma in situ at 5 years (OR 2.37, CI 1.45-3.86). CONCLUSION: Prior radiation is associated with lower grade and stage of bladder tumors in addition to worse cancer-specific survival.

Internalization of benzylisoquinoline alkaloids by resting and activated bone marrow-derived mast cells utilizes energy-dependent mechanisms.

OBJECTIVE AND DESIGN: Drug delivery to inflammatory cells is dependent upon poorly understood, complex endocytic processes. Berberine (BBR), a benzylisoquinoline alkaloid, binds to heparin and targets glycosaminoglycan-rich granules in mast cells (MC), but the mechanism of BBR internalization is unknown. METHODS: BMMC were treated with various concentrations of BBR for different amounts of time and BBR internalization was assessed by flow cytometry and fluorescence microscopy. BMMC were pretreated with endocytic inhibitors or a growth factor (IL-3) prior to BBR exposure to access mechanisms of its internalization. RESULTS: After 24 h, 48 ± 0.8% of BMMC internalized BBR and this process was dependent upon temperature and the presence of glucose in the medium. Methanol fixation reduced BBR internalization, suggesting the involvement of an energy-dependent active transport mechanism. To determine mode of internalization, BBR was encapsulated into Lipofectamine TM lipoplexes since these are known to circumvent classical endocytic pathways. Incorporating BBR into lipoplexes decreased BBR internalization by 26% and 10% (10 µg/ml and 100 µg/ml Lipo-BBR respectively) by BMMC. BBR endocytosis was significantly reduced by Latrunculin B (88%), Cytochalasin B (87%), Chloroquine (86.5%) and 3-methyladenine (91%), indicating that actin polymerization, lysosomal pH and lysosomal self-degradation via the autophagy pathway was involved. In contrast, IL-3 treatment significantly enhanced BBR endocytosis (54% by 40 ng/ml IL-3) suggesting that IL-3 signaling pathways play a role in internalization. CONCLUSIONS: Our data suggests that internalization of BBR by resting and IL-3-activated BMMC utilizes an energy-dependent pathway that is dependent upon glucose metabolism and temperature. Furthermore, this process requires actin polymerization and lysosomal trafficking. These data suggest internalization of benzylisoquinoline compounds is an active and complex process.

Rapid chiral separation of potential antibiotics using supercritical fluid chromatography.

WHO is searching most active antibiotics due to the bacterial resistance problem. The activities of the racemic antibiotics may be augment by preparing optically active antibiotics by the chiral separation. Chiral separation of potential antibiotics such as cefotaxime and ofloxacin was studied using amylose-based packing chiral stationary phases (CSPs) such as Chiralpak IA and Chiralpak IG. Supercritical fluid chromatography (SFC) was employed to carry out this study. Both immobilized CSPs such as Chiralpak IA and IG have sown remarkable selectivity for the reported drugs by using SFC. The values of retention factor (k) for ofloxacin enantiomers were 9.63 and 11.81, followed by 2.94 and 5.96 for cefotaxime enantiomers. The values of separation factor (α) for both the reported drugs were 1.22 and 2.03, respectively Similarly, the values of resolution factor (Rs) for both the enantio-selective drugs were 1.49 and 2.06, separately and respectively. The chiral recognition mechanism was developed and it was observed that the π-π interactions are playing a major role. The developed method is effective, reproducible, eco-friendly, and may be used to discriminate the enantiomers of the reported drugs in any sample.

Chiral separation of ß-blockers by supercritical fluid chromatography using Chiralpak-IG and Chiralpak IBN-5 columns.

Chiral separation of ß-blockers is performed by utilizing the supercritical fluid chromatographic method. The chiral columns utilized were Chiralpak IG and Chiralpak IBN-5. The finest mobile phase was CO2 -0.2% TEA in methanol (60:40). The values atenolol enantiomers retention factors were 6.39 and 8.98. These values for propranolol enantiomers were 3.39 and 4.06. These values for betaxolol enantiomers were 4.08 and 4.68. The separation and resolution factor values for atenolol, propranolol, and betaxolol were 1.41 and 3.33, 1.19 and 2.23, and 1.15 and 1.87, separately and respectively. By comparison, it was observed that Chiralpak IG column is better than Chiralpak IBN-5 column. Supercritical fluid chromatography has been found as the best analytical technique due to its high speed, being eco-friendly, and being economic. The various most probable interactions responsible for the chiral resolution are hydrogen bonding, dipole-dipole interactions, steric effect, and π-π interactions. The reported methods are effective, efficient, and reproducible and may be used to separate and identify atenolol, propranolol, and betaxolol in any unknown samples.

Chiral separation of calcium channel antagonists by SFC and HPLC using different immobilized chiral stationary phases.

Supercritical fluid chromatography and high-performance liquid chromatography techniques are popular for the chiral separations of different drugs and pharmaceuticals. Therefore, this article describes a comparative study of the chiral separation of some calcium channel antagonists such as verapamil, gallopamil, and nisoldipine. The columns used were Chiralpak IG and Chiralpak ID (250 mm × 4.6 mm, 5.0 µm). The separation was achieved by using a variety of mobile phases in both techniques. The retention, separation, and resolution factors in SFC were in the range of 1.36-7.30, 1.09-1.72, and 1.16-3.47, while these values in the case of HPLC were 1.03-2.42, 1.12-1.35, and 0.49-2.46. The complete resolution of gallopamil and verapamil was achieved successfully. The chiral recognition was controlled by hydrogen bondings, π-π interactions, dipole induced dipole interactions, van der Waal forces, and steric effects. SFC was found to be a better technique than HPLC because of quick separation, good separation power, economic, environment-friendly, and green technology.

A comparative study of chiral separation of proton pump inhibitors by supercritical fluid chromatography and high-performance liquid chromatography.

A comparative study of chiral separation of pantoprazole and rabeprazole is carried out using supercritical fluid chromatography and high-performance liquid chromatography. The columns used were Chiralpak IA and Chiralpak IE. The best mobile phase in supercritical fluid chromatography was carbon dioxide-0.2% triethylamine in methanol (60:40) and 0.1% triethylamine in n-hexane-ethanol (50:50) in high-performance liquid chromatography. For supercritical fluid chromatography, values of the retention factor of pantoprazole enantiomers were 3.97 and 4.88. These values for rabeprazole enantiomers were 6.10 and 7.52. The values of separation and resolution factor for pantoprazole and rabeprazole were 1.23 and 1.23 and 2.20 and 3.36, respectively. Similarly, for high-performance liquid chromatography, the values of retention factor for enantiomers of pantoprazole were 4.02 and 7.32. These values for rabeprazole enantiomers were 5.32 and 7.88, respectively. The values of separation and resolution factor for pantoprazole and rabeprazole were 1.82 and 1.48 and 9.22 and 6.58, respectively. A comparison was carried out, which confirmed supercritical fluid chromatography as the best method due to its fastness, eco-friendly, and inexpensiveness. The reported methods are effective, efficient, and reproducible and may be used to separate and identify pantoprazole and rabeprazole in any unknown samples.

Quercetin and Resveratrol Differentially Decrease Expression of the High-Affinity IgE Receptor (FcεRI) by Human and Mouse Mast Cells.

Mast cells (MC) synthesize and store proinflammatory mediators and are centrally important in atopic diseases such as asthma and atopic dermatitis. Quercetin a and resveratrol are plant derived polyphenolic compounds with anti-inflammatory properties that inhibit MC degranulation and mediator release. However, the underlying mechanism of these inhibitory effects on MC is poorly understood and it is unclear whether this is a general effect on all MC phenotypes. We have characterized and compared the effects of quercetin with resveratrol on human (LAD2) and mouse (MC/9 and BMMC) MC mediator release, receptor expression and FcεRI signaling to better understand the mechanisms involved in quercetin and resveratrol-mediated inhibition of MC activation. Quercetin significantly decreased the expression of FcεRI by BMMC and MC/9, although the effects on MC/9 were associated with a significant reduction in cell viability. Quercetin also inhibited antigen-stimulated TNF release by BMMC. Although neither quercetin nor resveratrol significantly altered antigen-stimulated BMMC degranulation or downstream signaling events such as phosphorylation of spleen tyrosine kinase (SYK) or extracellular signal-regulated kinase 1/2 (ERK), resveratrol inhibited ERK phosphorylation and FcεRI- stimulated degranulation in LAD2. Our data suggests that quercetin and resveratrol inhibit human and mouse MC differentially and that these effects are associated with modification of FcεRI expression, signaling (phosphorylation of SYK and ERK) and mediator release.

The Complexity of Sesquiterpene Chemistry Dictates Its Pleiotropic Biologic Effects on Inflammation.

Sesquiterpenes (SQs) are volatile compounds made by plants, insects, and marine organisms. SQ have a large range of biological properties and are potent inhibitors and modulators of inflammation, targeting specific components of the nuclear factor-kappaB (NF-κB) signaling pathway and nitric oxide (NO) generation. Because SQs can be isolated from over 1600 genera and 2500 species grown worldwide, they are an attractive source of phytochemical therapeutics. The chemical structure and biosynthesis of SQs is complex, and the SQ scaffold represents extraordinary structural variety consisting of both acyclic and cyclic (mono, bi, tri, and tetracyclic) compounds. These structures can be decorated with a diverse range of functional groups and substituents, generating many stereospecific configurations. In this review, the effect of SQs on inflammation will be discussed in the context of their complex chemistry. Because inflammation is a multifactorial process, we focus on specific aspects of inflammation: the inhibition of NF-kB signaling, disruption of NO production and modulation of dendritic cells, mast cells, and monocytes. Although the molecular targets of SQs are varied, we discuss how these pathways may mediate the effects of SQs on inflammation.

Infertility Counseling and Misattributed Paternity: When Should Physicians Become Involved in Family Affairs?

Infertility specialists may be confronted with the ethical dilemma of whether to disclose misattributed paternity (MP). Physicians should be prepared for instances when an assumed father's evaluation reveals a condition known for lifelong infertility, for example, congenital bilateral absence of vas deferens (CBAVD). When there is doubt regarding a patient's comprehension of his diagnosis, physicians must consider whether further disclosure is warranted. This article describes a case of MP with ethics analysis that concludes that limited nondisclosure is most consistent with a physician's principled duties to inform, to respect patients' autonomy, and to employ nonmaleficence (including the avoidance of psychosocial harms).

Desire to stay shorter time at the shopping mall: insight from protection motivation (PMT), behavioral inhibition system (BIS), reactance, and expectancy theories.

After withdrawing the movement control order (MCO), new variant (Omicron) of COVID-19 returns as an outbreak again. Therefore, consumers are very much informed by various media to be more cautious in visiting shopping malls and spend less time in there. The purpose of this study was to identify the predictors influencing the desire to stay shorter at the shopping mall. This study was conducted in Malaysia, with the application of three psychological theories and one behavioural theory. This is quantitative research based on an online cross-sectional survey design. Data were collected from 296 respondents, by applying the online snowball sampling method through numerous media platforms i.e., Viber, WhatsApp, Messenger, and other apps in three severely affected cities in Malaysia i.e., Selangor state, Putrajaya, and Kuala Lumpur. SmartPLS was used to analyse the data. Using structural equation modelling, this study result shows risk, protection motivation, and fear have a significant effect on the desire to stay a shorter time at the shopping mall. Social norm moderates the association between fear and the desire to spend a shorter time at the shopping mall. These findings, highlight the need for a more empirical study to design more robust strategies, and a safer and risk-free shopping mall environment.