Novel targets and therapies for keloid Naik, P. P.
Clinical and experimental dermatology,
March 2022, 2022-Mar, 2022-03-00, 20220301, Volume:
47, Issue:
3
Journal Article
Peer reviewed
Summary
Keloids are the result of aberrant tissue scarring typically occurring in injured skin, and are caused by the overgrowth of granulation tissue or collagen type III during the healing process. ...There is a genetic component, thus a predisposition can be genetically transmitted. Keloids are difficult to treat because of their postexcisional recurrence, and they have an impact on patient quality of life due to psychological distress caused by cosmetic concerns and functional disability. Treatment ranges from classic corticosteroid therapy to multimodal approaches such as injections, cryotherapy, laser, radiation, radiofrequency ablation and extracorporeal shockwave therapy. Recent discoveries into the pathogenesis of keloid have enabled clinicians to expand the therapeutic options for treatment. The aim of this paper was to review the literature, clarify the general concept of keloid development, and assess emerging treatment options such as stem cell therapy, mitomycin C, bleomycin, interferon, botulinum toxin type A, calcium channel blockers, angiotensin‐converting enzyme inhibitors and fat grafting, and the evolutionary advancement towards epigenetic modifications and gene therapy.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
Psychiatryai.com is a prototype Artificial Intelligence (AI) and Data Science (DS) platform and research project developed for my Evidence-Based Healthcare (EBHC) course at University of ...Oxford in MSc studies (Kellogg College). This is a singular, multi-disciplinary, and beta-testing project in Computing Science, Psychiatry, and Mental Health for oral presentation at EPA 2023.
Objectives
AI and DS in Psychiatry and Mental Health have emerged as important research areas in the post Covid-19 pandemic era. This prototype University project (Psychiatryai.com) was launched on 22nd November 2021. It aims to develop a free, secure, and open access platform in
near
real-time about psychiatry and mental health evidence-based research - for healthcare professionals, doctors, and researchers in psychiatry. The project also aims to integrate findings from the Goldacre Review (2022) into practice and develop novel computing solutions utilising AI and DS, and present findings.
Methods
A WordPress site (Psychiatryai.com) was developed with syndicated RSS feeds across 330 psychiatry topics and refreshed by data servers hourly, 24 hours a day, 7 days a week. A total of 43 WordPress plugins were utilised to develop this secure platform. The site is powered by intuitive data modelling and analytics in near real-time and available in open access coding format for peer-review, future development, and research. The primary sources of live evidence for the project are PubMed and University of Helsinki, Finland. The server performance data analytics will be available for poster presentation at EPA 2023. This includes full statistical results and discussion since its inception and launch (including traffic, MESH tags, and PubMed ID), and robust technical analysis and performance outcomes - available freely online to promote research in psychiatry and mental health.
Results
Knowledge Synthesis and Dissemination:
Total Words: 4356886 *
Live Psychiatry and Mental Health Citations from PubMed: Exceeds 325000
Total Evidence Alerts Published: 54391 *
Total Algorithms/Topics: 330
Total site visitors: 8023 *
* Since launch of Psychiatryai.com on 22 November 2021 inclusive to 31 October 2022
Conclusions
Psychiatryai.com was able to demonstrate succesful development of an effective and viable platform to study AI and DS in Psychiatry and Mental Health, as evidenced by results table. The platform has also incorporated findings from the Goldacre Review (2022) and aims to continue to collect valuable insights towards
full
real-time data analytics and dissemination of peer-reviewed current evidence in the future. The emergence of these technologies will be useful in settings such as disaster psychiatry, psychiatry e-training and research, and e-mental health awareness/promotion ahead.
Disclosure of Interest
P. Naik Consultant of: Dr Paras Naik (Psychiatryai.com) Non-profit University Project
Globally, food waste (FW) is found to be one of the major constituents creating several hurdles in waste management. On the other hand, the energy crisis is increasing and the limited fossil fuel ...resources available are not sufficient for energy needed for emerging population. In this context, biohydrogen production approach through valorization of FW is emerging as one of the sustainable and eco-friendly options. The present review explores FW sources, characteristics, and dark fermentative production of hydrogen along with its efficiency. FW are highly biodegradable and rich in carbohydrates which can be efficiently utilized by anaerobic bacteria. Based on the composition of FW, several pretreatment methods can be adapted to improve the bioavailability of the organics. By-products of dark fermentation are organic acids that can be integrated with several secondary bioprocesses. The versatility of secondary products is ranging from energy generation to biochemicals production. Integrated approaches facilitate in enhanced energy harvesting along with extended wastewater treatment. The review also discusses various parameters like pH, temperature, hydraulic retention time and nutrient supplementation to enhance the process efficiency of biohydrogen production. The application of solid-state fermentation (SSF) in dark fermentation improves the process efficiency. Dark fermentation as the key process for valorization and additional energy generating process can make FW the most suitable substrate for circular economy and waste based biorefinery.
Display omitted
•Carbohydrate rich food waste (FW) has high potential for biohydrogen production.•Biohydrogen production from FW treatment also addresses waste management.•Biorefineries and circular economy can be developed through FW valorization.•Lab scale to pilot scale experiences with dark fermentation were documented.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The sickle hemoglobin (HbS) point mutation has independently undergone evolutionary selection at least five times in the world because of its overwhelming malarial protective effects in the ...heterozygous state. In 1949, homozygous Hb S or sickle cell disease (SCD) became the first inherited condition identified at the molecular level; however, since then, both SCD and heterozygous Hb S, sickle cell trait (SCT), have endured a long and complicated history. Hasty adoption of early mass screening programs for SCD, recent implementation of targeted screening mandates for SCT in athletics, and concerns about stigmatization have evoked considerable controversy regarding research and policy decisions for SCT. Although SCT is a largely protective condition in the context of malaria, clinical sequelae, such as exercise-related injury, renal complications, and venous thromboembolism can occur in affected carriers. The historical background of SCD and SCT has provided lessons about how research should be conducted in the modern era to minimize stigmatization, optimize study conclusions, and inform genetic counseling and policy decisions for SCT.
Tight junction (TJ) proteins are essential for mediating interactions between adjacent cells and coordinating cellular and organ responses. Initial investigations into TJ proteins and junctional ...adhesion molecules (JAM) in cancer suggested a tumor-suppressive role where decreased expression led to increased metastasis. However, recent studies of the JAM family members JAM-A and JAM-C have expanded the roles of these proteins to include protumorigenic functions, including inhibition of apoptosis and promotion of proliferation, cancer stem cell biology, and epithelial-to-mesenchymal transition. JAM function by interacting with other proteins through three distinct molecular mechanisms: direct cell-cell interaction on adjacent cells, stabilization of adjacent cell surface receptors on the same cell, and interactions between JAM and cell surface receptors expressed on adjacent cells. Collectively, these diverse interactions contribute to both the pro- and antitumorigenic functions of JAM. In this review, we discuss these context-dependent functions of JAM in a variety of cancers and highlight key areas that remain poorly understood, including their potentially diverse intracellular signaling networks, their roles in the tumor microenvironment, and the consequences of posttranslational modifications on their function. These studies have implications in furthering our understanding of JAM in cancer and provide a paradigm for exploring additional roles of TJ proteins.
Mitogen-activated protein kinases (MAPKs) are expressed in platelets and are activated downstream of physiological agonists. Pharmacological and genetic evidence indicate that MAPKs play a ...significant role in hemostasis and thrombosis, but it is not well understood how MAPKs are activated upon platelet stimulation. Here, we show that apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP3K family, is expressed in both human and murine platelets. ASK1 is rapidly and robustly activated upon platelet stimulation by physiological agonists. Disruption of Ask1 (Ask1−/−) resulted in a marked functional defect in platelets. Ask1−/− platelets showed an impaired agonist-induced integrin αIIbβ3 activation and platelet aggregation. Although there was no difference in Ca2+ rise, platelet granule secretion and thromboxane A2 (TxA2) generation were significantly attenuated in Ask1−/− platelets. The defective granule secretion observed in Ask1−/− platelets was a consequence of impaired TxA2 generation. Biochemical studies showed that platelet agonists failed to activate p38 MAPK in Ask1−/− platelets. On the contrary, activation of c-Jun N-terminal kinases and extracellular signal-regulated kinase 1/2 MAPKs was augmented in Ask1−/− platelets. The defect in p38 MAPK results in failed phosphorylation of cPLA2 in Ask1−/− platelets and impaired platelet aggregate formation under flow. The absence of Ask1 renders mice defective in hemostasis as assessed by prolonged tail-bleeding times. Deletion of Ask1 also reduces thrombosis as assessed by delayed vessel occlusion of carotid artery after FeCl3-induced injury and protects against collagen/epinephrine-induced pulmonary thromboembolism. These results suggest that the platelet Ask1 plays an important role in regulation of hemostasis and thrombosis.
•ASK1 regulates TxA2 generation through p38 MAPK-dependent phosphorylation of cPLA2.•Because of impaired platelet function, Ask1−/− mice are protected from arterial thrombosis and pulmonary thromboembolism.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
In the present paper a series of triphenylphosphine complexes containing mixed ligands like 2-aminothiazole (Ath) and 2-aminotriazole (Atz) have been prepared. The complexes are of the formula MCl
3
...((Pph
3
)(Ath)
2
and MCl
3
((Pph
3
)(Atz)
2
, M = Ru(III), Ce(III) and La(III). These complexes were characterized by different spectral techniques. Additionally, the computational study has been performed using density functional theory (DFT) and the calculation is used to examine the electronic structure of the synthesized complexes. The biological activities of all the synthesized complexes were evaluated and the comparative account in properties between the triphenylphosphine metal complexes containing 2-aminothiazole and 2-aminotriazole ligands has been made. The DNA-binding property of these metal complexes was investigated using electronic absorption spectroscopy and fluorescence spectroscopy. The antibacterial and antifungal activity against bacterial species (Gram −ve bacteria:
Escherichia coli
,
Salmonella typhi
) and (Gram +ve bacteria: (
Staphylococcus aureus
and
Bacillus subtilis
) and fungi (
Aspergillus niger
and
Candida albicans
). The antioxidant study was carried out against the 2,2-diphenyl-1-picrylhydrazyl radical (DPPH
·
) which showed that the metal complexes are good antioxidant, as compared to BHT. Further, the in-silico molecular docking study was performed to predict the possible binding sites of the metal complexes.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The genetic and molecular basis of sickle cell disease (SCD) has long since been characterized but the pathophysiological basis is not entirely defined. How a red cell hemolytic disorder initiates ...inflammation, endothelial dysfunction, coagulation activation and eventually leads to vascular thrombosis, is yet to be elucidated. Recent evidence has demonstrated a high frequency of unprovoked/recurrent venous thromboembolism (VTE) in SCD, with an increased risk of mortality among patients with a history of VTE. Here, we thoroughly review the molecular basis for the prothrombotic state in SCD, specifically highlighting emerging evidence for activation of overlapping inflammation and coagulation pathways, that predispose to venous thromboembolism. We share perspectives in managing venous thrombosis in SCD, highlighting innovative therapies with the potential to influence the clinical course of disease and reduce thrombotic risk, while maintaining an acceptable safety profile.
This article reports world averages of measurements of
b
-hadron,
c
-hadron, and
τ
-lepton properties obtained by the Heavy Flavor Averaging Group using results available through summer 2016. For the ...averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters,
C
P
violation parameters, parameters of semileptonic decays, and Cabbibo–Kobayashi–Maskawa matrix elements.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is believed that activation of c-Src bound to the integrin β3 subunit initiates outside-in signaling. The involvement of αIIb in outside-in signaling is poorly understood.
We have previously shown ...that CIB1 specifically interacts with the cytoplasmic domain of αIIb and is required for αIIbβ3 outside-in signaling. Here we evaluated the role of CIB1 in regulating outside-in signaling in the absence of inside-out signaling.
We used αIIb cytoplasmic domain peptide and CIB1-function blocking antibody to inhibit interaction of CIB1 with αIIb subunit as well as Cib1-/- platelets to evaluate the consequence of CIB1 interaction with αIIb on outside-in signaling.
Fibrinogen binding to αIIbβ3 results in calcium-dependent interaction of CIB1 with αIIb, which is not required for filopodia formation. Dynamic rearrangement of cytoskeleton results in CIB1-dependent recruitment of FAK to the αIIb complex and its activation. Disruption of the association of CIB1 and αIIb by incorporation of αIIb peptide or anti-CIB1 inhibited both FAK association and activation. Furthermore, FAK recruitment to the integrin complex was required for c-Src activation. Inhibition of c-Src had no effect on CIB1 accumulation with the integrin at the filopodia, suggesting that c-Src activity is not required for the formation of CIB1-αIIb-FAK complex.
Our results suggest that interaction of CIB1 with αIIb is one of the early events occurring during outside-in signaling. Furthermore, CIB1 recruits FAK to the αIIbβ3 complex at the filopodia where FAK is activated, which in turn activates c-Src, resulting in propagation of outside-in signaling leading to platelet spreading.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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