An interpretative phenomenological analysis of the lived experience of people with multimorbidity in low- and middle-income countries.

People living with multimorbidity (PLWMM) have multiple needs and require long-term personalised care, which necessitates an integrated people-centred approach to healthcare. However, people-centred care may risk being a buzzword in global health and cannot be achieved unless we consider and prioritise the lived experience of the people themselves. This study captures the lived experiences of PLWMM in low- and middle-income countries (LMICs) by exploring their perspectives, experiences, and aspirations.We analysed 50 semi-structured interview responses from 10 LMICs across three regions-South Asia, Latin America, and Western Africa-using an interpretative phenomenological analysis approach.The bodily, social, and system experiences of illness by respondents were multidirectional and interactive, and largely captured the complexity of living with multimorbidity. Despite expensive treatments, many experienced little improvements in their conditions and felt that healthcare was not tailored to their needs. Disease management involved multiple and fragmented healthcare providers with lack of guidance, resulting in repetitive procedures, loss of time, confusion, and frustration. Financial burden was exacerbated by lost productivity and extreme finance coping strategies, creating a vicious cycle. Against the backdrop of uncertainty and disruption due to illness, many demonstrated an ability to cope with their conditions and navigate the healthcare system. Respondents' priorities were reflective of their desire to return to a pre-illness way of life-resuming work, caring for family, and maintaining a sense of independence and normalcy despite illness. Respondents had a wide range of needs that required financial, health education, integrated care, and mental health support.In discussion with respondents on outcomes, it appeared that many have complementary views about what is important and relevant, which may differ from the outcomes established by clinicians and researchers. This knowledge needs to complement and be incorporated into existing research and treatment models to ensure healthcare remains focused on the human and our evolving needs.

Exploring Non-Toxic Lower Dimensional Perovskites for Next-Generation X-Ray Detectors.

Owing to their extraordinary photophysical properties, organometal halide perovskites are emerging as a new material class for X-ray detection. However, the existence of toxic lead makes their commercialization questionable and should readily be replaced. Accordingly, several lead alternatives have been introduced into the framework of conventional perovskites, resulting in various new perovskite dimensionalities. Among these, Pb-free lower dimensional perovskites (LPVKs) not only show promising X-ray detecting properties due to their higher ionic migration energy, wider and tunable energy bandgap, smaller dark currents, and structural versatility but also exhibit extended environmental stability. Herein, first, the structural organization of the PVKs (including LPVKs) is summarized. In the context of X-ray detectors (XDs), the outstanding properties of the LPVKs and active layer synthesis routes are elaborated afterward. Subsequently, their applications in direct XDs are extensively discussed and the device performance, in terms of the synthesis method, device architecture, active layer size, figure of merits, and device stability are tabulated. Finally, the review is concluded with an in-depth outlook, thoroughly exploring the present challenges to LPVKs XDs, proposing innovative solutions, and future directions. This review provides valuable insights into optimizing non-toxic Pb-free perovskite XDs, paving the way for future advancements in the field.

A dilemma of patients: poor quality administration of tertiary care hospitals: a cross-sectional study.

Introduction: The study focuses on healthcare delivery standards in Pakistan's tertiary care hospitals. Poor accountability and a lack of financial and human resources are the main contributing factors to a hospital's substandard performance and low patient satisfaction rates. Feedback surveillance forms are the Achilles tendon in the quality improvement of a facility, and this practice is, unfortunately, not widely practiced in the hospitals of Pakistan. Through this paper and experience, the authors hope to shed light on the need for regular feedback surveys and implementing their results to improve healthcare quality. Settings and Design: A prospective, observational study of seven tertiary care hospitals in Pakistan. Materials and Methods: The data was collected using a survey form. Each survey form was filled out by a team comprising three public health professionals who observed the hospital and its functioning without interfering with its workings. The questionnaire was developed with the help of Tools for Assessing the Operationality of District Health Systems: Health Facility Questionnaire designated in the respective facilities. The analysis was then draughted as a qualitative narrative review. Finally, the review was broken down into an assessment of the hospital's outpatient clinic setting, inpatient department, emergency department and other departments. Results: The survey was conducted at seven public sector hospitals in three major cities of Pakistan. The survey focused on administrative and nonmedical parameters of healthcare facilities. Overall, the hospitals of Lahore and Islamabad lacked mass casualty apparatus and cleanliness, and staff behaviour can be improved. The hospitals in Rawalpindi have mass casualty apparatuses in place. However, they need improvement in accessibility services and hygiene and staff attitude. Conclusions: The survey showed that all the hospitals had good access and accessibility, and the directions were clearly marked for the visitors. The hospital staff is knowledgeable about the hospital, but their behaviour needs to be improved. Also, the quality of the cleanliness and waiting areas is fair but needs improvements. Finally, regular cheques via regular feedback and quality assessments can improve healthcare delivery.

Designing a novel chimeric multi-epitope vaccine subunit against Staphylococcus argenteus through artificial intelligence approach integrating pan-genome analysis, in vitro identification, and immunogenicity profiling.

Staphylococcus argenteus is a newly identified pathogen that causes respiratory tract infections, skin infections, such as cellulitis, abscesses, and impetigo, and currently, there is no licensed vaccine available against it. To develop a vaccine against S. argenteus, a bacterial pan-genome analysis was applied to identify potential vaccine candidates. A total of 4908 core proteins were retrieved and utilized for identifying four proteins, including SG38 Panton-Valentine leukocidin LukS-PV protein, SG62 staphylococcal enterotoxin type A protein, SG39 enterotoxin B protein, and SG43 enterotoxin type C3 protein as potential vaccine candidates. Epitopes were predicted for these proteins using different types of B and T-cell epitope prediction tools, and only those with a non-toxic profile, antigenic, non-allergenic, and immunogenic were selected. The selected epitopes were linked to each other to form a multi-epitope vaccine construct, which was further linked to the PADRE sequence (AKFVAAWTLKAAA) and 50s ribosomal L7/L12 protein to enhance the vaccine's antigenicity. The three-dimensional structure of the vaccine construct was assessed to determine its binding affinity with key Toll-like receptor 9 (TLR-9) and Toll-like receptor 5 (TLR-5) immune cell receptors. Our findings demonstrate that the vaccine exhibits favorable binding interactions with these immune cell receptors, indicating its potential efficacy. Molecular dynamic simulations further confirmed the accessibility of vaccine epitopes to the host immune system, substantiating its ability to elicit protective immune responses. Taken together, this study highlights the promising candidacy of the modeled vaccine construct for future in vivo and in vitro experimental investigations.Communicated by Ramaswamy H. Sarma.

Phonon-Mediated Quasiparticle Lifetime Renormalizations in Few-Layer Hexagonal Boron Nitride.

Understanding the collective behavior of the quasiparticles in solid-state systems underpins the field of nonvolatile electronics, including the opportunity to control many-body effects for well-desired physical phenomena and their applications. Hexagonal boron nitride (hBN) is a wide-energy-bandgap semiconductor, showing immense potential as a platform for low-dimensional device heterostructures. It is an inert dielectric used for gated devices, having a negligible orbital hybridization when placed in contact with other systems. Despite its inertness, we discover a large electron mass enhancement in few-layer hBN affecting the lifetime of the π-band states. We show that the renormalization is phonon-mediated and consistent with both single- and multiple-phonon scattering events. Our findings thus unveil a so-far unknown many-body state in a wide-bandgap insulator, having important implications for devices using hBN as one of their building blocks.

The HDAC2/YY1/c-Myc signaling axis regulates lung cancer cell migration and proliferation.

Lung cancer is among the most aggressive types of malignant tumors that contributes to cancer-associated deaths worldwide with a high occurrence and fatality rate. Histone deacetylase 2 (HDAC2), prevent the aberrant transcription of a number of genes that are primarily responsible for controlling the cell cycle, cell proliferation, and signaling pathways in numerous cancers. Previous studies reported the role of HDACs and YY1 in the growth and development of several cancers. Although, it is noteworthy that remarkable efforts have been taken for the treatment of lung cancer using molecularly targeted therapies and chemotherapeutic agents, but the outcome is still poor for this critically persistent cancer. Therefore, the aim of the present study is to identify an efficacious, novel therapeutic biomarkers for the successful diagnosis of lung cancer at the early stage of the disease and the molecular insights involved. In the present study, qPCR and western bot data revealed that the expression level of HDAC2 and YY1 were upregulated in the cell lines and tumor samples of lung cancer patients. Moreover, MTT, qPCR, western blot, cell cycle analysis, and migration assays showed that inhibition of HDAC2 reduced YY1 expression, similarly, depletion of YY1 using knockdown approach inhibited the proliferation, migration, invasion, and blockage of the cell cycle by suppressing c-Myc in lung cancer cell lines. In conclusion, the current study findings support the notion that HDAC2's anticancer role was attributed through YY1 regulation by targeting c-Myc and could act as potential novel candidate biomarker for the lung cancer diagnosis.

Doxorubicin induced ROS-dependent HIF1α activation mediates blockage of IGF1R survival signaling by IGFBP3 promotes cardiac apoptosis.

Doxorubicin (Dox) causes the generation of intracellular reactive oxygen species (ROS) and inactivates insulin-like growth factor 1 (IGF1) signaling, leading to cardiomyocyte apoptosis. IGF-binding protein 3 (IGFBP3) is the most abundant circulating IGF1 carrier protein with high affinity, which has been reported to mediate ROS-induced apoptosis. Hypoxia-inducible factor 1α (HIF1A), an upstream protein of IGFBP3 is regulated by prolyl hydroxylase domain (PHD) through hydroxylation. In this study, we investigated the role of IGFBP3, HIF1A, and PHD in Dox-induced cardiac apoptosis.Cells challenged with 1 µM Dox for 24 h increased ROS generation, augmented intracellular and secreted IGFBP3 levels, and reduced IGF1 signaling. Further, we showed that Dox enhanced the extracellular association of IGF1 with IGFBP3. Moreover, echocardiography parameters, especially ejection fraction (EF) and fractional shortening (FS) were significantly reduced in ventricle tissue of Dox challenged rats. Notably, siRNA approach against IGFBP3 or an anti-IGFBP3 antibody rescued Dox-induced cardiac apoptosis, mitochondrial ROS, and the decrease in the IGF1 signaling activity. Furthermore, silencing HIF1A either using siRNA or inhibitor downregulated intracellular IGFBP3, rescued apoptosis, mitochondrial generation, and reduction in IGF1 signaling. Finally, western blot data revealed that ROS scavenger reversed Dox-induced cardiac apoptosis, increased levels of HIF1A and secreted IGFBP3, and decreased IGF1 survival signaling and PHD expression.These findings suggest that Dox-induced ROS generation suppressed PHD, which might stabilize nuclear HIF1A protein, leading to increased IGFBP3 expression and secretion. This in turn results in enhanced extracellular association of the latter with IGF1 and blocks IGF1 pro-survival signaling and may result in inducing cardiac apoptosis.

Worldwide outcomes of nasal transposition of the split lateral rectus muscle for strabismus associated with 3rd-nerve palsy.

BACKGROUND/AIMS: To determine success rate and complications associated with nasal transposition of the split lateral rectus muscle (NTSLR) for treating strabismus from 3rd-nerve palsy. METHODS: An international, multicentre, registry of patients with unilateral 3rd-nerve palsy treated with NTSLR was created. Patients with concurrent surgery on the contralateral eye were excluded. Primary outcome was horizontal alignment within 15 prism dioptres (PD) of orthotropia. Incidence of technical difficulties and vision-threatening complications by 6 months post-procedure were reported. RESULTS: Ninety-eight patients met inclusion criteria. Median age was 33.5 years (IQR 10.75-46). Aetiologies included congenital (31%), neoplastic (16%) and traumatic (15%). Twenty-five per cent of patients had prior ipsilateral strabismus surgery. Median exotropia decreased from 70PD preoperatively (IQR 50-90) to 1PD postoperatively (IQR 0-15.5), with a success rate of 69%. Performing concurrent superior oblique muscle tenotomy (SOT) was independently associated with success (p=0.001). Technical challenges occurred in 30% of cases, independently associated with a history of ipsilateral strabismus surgery (p=0.01). Eleven per cent of patients had vision-threatening complications, independently associated with more posterior placement of the split lateral rectus (LR) muscle (p<0.001), and most commonly transient serous choroidal effusion. Surgical placement of the split LR muscle within 4.25 mm of the medial rectus (MR) muscle insertion reduced this risk. CONCLUSION: NTSLR significantly improved primary position alignment altered by 3rd-nerve palsy. Concurrent SOT and placement of the split LR muscle ≤4.25 mm posterior to the MR muscle insertion optimised outcomes. NTSLR proved technically challenging when prior ipsilateral strabismus surgery had been performed.

Highly Efficient Inherent Linearly Polarized Electroluminescence from Small-Molecule Organic Single Crystals.

Small-molecule organic single crystals (SCs) with an inherent in-plane anisotropic nature enable direct linearly polarized light emission without the need for spatially separated polarizers and complex optical structures. However, the device performance is severely restricted by the starvation of appropriate SC emitters and the difficulty in the construction of efficient SC electroluminescence (EL) devices, leading to a low external quantum efficiency (EQE) of usually smaller than 1.5%. Here, highly efficient inherent linearly polarized light-emitting diodes (LP-LEDs) are demonstrated by exploiting 2,6-diphenylanthracene (DPA) SCs as intrinsically polarized emitters. The LP-LEDs exhibit a 2.5-fold enhanced maximum EQE of 3.38%, which approaches the theoretical limit for the DPA SC-based EL device and is the highest among organic SC-based LEDs reported thus far. More importantly, a high degree of polarization (DOP) up to 0.74 is achieved for the intrinsically polarized EL emission of the DPA SC-based LP-LEDs. By leveraging the highly efficient LP-LED, an interchip polarized optical communication system consisting of organic SCs is demonstrated for the first time. This work creates a solid foundation for the exploitation of a vast new library of small-molecule organic SCs for LP-LEDs and carries broad implications for polarized optics and relevant optoelectronic devices.

Caproic Acid-Producing Bacteria in Chinese Baijiu Brewing.

Caproic acid can be used as spices, preservatives, animal feed additives, and biofuels. At the same time, caproic acid plays an important role in Chinese Baijiu. It is the precursor substance for the synthesis of ethyl caproate, which directly affects the quality of Chinese Baijiu. Caproic acid-producing bacteria are the main microorganisms that synthesize caproic acid in Chinese Baijiu, and the most common strain is Clostridium kluyveri. Caproic acid-producing bacteria synthesize n-caproic acid through reverse ß-oxidation to extend the carboxylic acid chain. This method mainly uses ethanol and lactic acid as substrates. Ethanol and lactic acid are converted into acetyl-CoA, and acetyl-CoA undergoes a series of condensation, dehydrogenation, dehydration, and reduction to extend the carboxylic acid chain. This review addresses the important issues of caproic acid-producing bacteria in the brewing process of Baijiu: the common caproic acid-producing bacteria that have been reported metabolic pathways, factors affecting acid production, biological competition pathways, and the effect of mixed bacteria fermentation on acid production. It is hoped that this will provide new ideas for the study of caproic acid-producing bacteria in Chinese Baijiu.

Protective effects of CHIP overexpression and Wharton's jelly mesenchymal-derived stem cell treatment against streptozotocin-induced neurotoxicity in rats.

Diabetic neuropathy is a common complication of diabetes mellitus, posing a challenge in treatment. Previous studies have indicated the protective role of mesenchymal stem cells against several disorders. Although they can repair nerve injury, their key limitation is that they reduce viability under stress conditions. We recently observed that overactivation of the carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP) considerably rescued cell viability under hyperglycemic stress and played an essential role in promoting the beneficial effects of Wharton's jelly-derived mesenchymal stem cells (WJMSCs). Thus, the present study was designed to unveil the protective effects of CHIP-overexpressing WJMSCs against neurodegeneration using in vivo animal model based study. In this study, western blotting observed that CHIP-overexpressing WJMSCs could rescue nerve damage observed in streptozotocin-induced diabetic rats by activating the AMPKα/AKT and PGC1α/SIRT1 signaling pathway. In contrast, these signaling pathways were downregulated upon silencing CHIP. Furthermore, CHIP-overexpressing WJMSCs inhibited inflammation induced in the brains of diabetic rats by suppressing the NF-κB, its downstream iNOS and cytokines signaling nexus and enhancing the antioxidant enzyme system. Moreover, TUNEL assay demonstrated that CHIP carrying WJMSCs suppressed the apoptotic cell death induced in STZ-induced diabetic group. Collectively, our findings suggests that CHIP-overexpressing WJMSCs might exerts beneficial effects, which may be considered as a therapeutic strategy against diabetic neuropathy complications.

High-Luminance Microsized CH3NH3PbBr3 Single-Crystal-Based Light-Emitting Diodes via a Facile Liquid-Insulator Bridging Route.

Micro-/nanosized organic-inorganic hybrid perovskite single crystals (SCs) with appropriate thickness and high crystallinity are promising candidates for high-performance electroluminescent (EL) devices. However, their small lateral size poses a great challenge for efficient device construction and performance optimization, causing perovskite SC-based light-emitting diodes (PSC-LEDs) to demonstrate poor EL performance. Here, we develop a facile liquid-insulator bridging (LIB) strategy to fabricate high-luminance PSC-LEDs based on single-crystalline CH3NH3PbBr3 microflakes. By introducing a blade-coated poly(methyl methacrylate) (PMMA) insulating layer to effectively overcome the problems of leakage current and possible short circuits between electrodes, we achieve the reliable fabrication of PSC-LEDs. The LIB method also allows us to systematically boost the device performance through crystal growth regulation and device architecture optimization. Consequently, we realize the best CH3NH3PbBr3 microflake-based PSC-LED with an ultrahigh luminance of 136100 cd m-2 and a half-lifetime of 88.2 min at an initial luminance of ∼1100 cd m-2, which is among the highest for organic-inorganic hybrid perovskite LEDs reported to date. Moreover, we observe the strong polarized edge emission of the microflake-based PSC-LEDs with a high degree of polarization up to 0.69. Our work offers a viable approach for the development of high-performance perovskite SC-based EL devices.

Carboxyl terminus of HSP70-interacting protein attenuates advanced glycation end products-induced cardiac injuries by promoting NFκB proteasomal degradation.

Advanced glycation end products (AGEs), which are highly reactive molecules resulting from persistent high-glucose levels, can lead to the generation of oxidative stress and cardiac complications. The carboxyl terminus of HSP70 interacting protein (CHIP) has been demonstrated to have a protective role in several diseases, including cardiac complications; however, the role in preventing AGE-induced cardiac damages remains poorly understood. Here, we found that elevated AGE levels impaired cardiac CHIP expression in streptozotocin-induced diabetes and high-fat diet-administered animals, representing AGE exposure models. We used the TUNEL assay, hematoxylin and eosin, Masson's trichrome staining, and western blotting to prove that cardiac injuries were induced in diabetic animals and AGE-treated cardiac cells. Interestingly, our results collectively indicated that CHIP overexpression significantly rescued the AGE-induced cardiac injuries and promoted cell survival. Moreover, CHIP knockdown-mediated stabilization of nuclear factor κB (NFκB) was attenuated by overexpressing CHIP in the cells. Furthermore, co-immunoprecipitation and immunoblot assay revealed that CHIP promotes the ubiquitination and proteasomal degradation of AGE-induced NFκB. Importantly, fluorescence microscopy, a luciferase reporter assay, electrophoretic mobility shift assay, and subcellular fractionation further demonstrated that CHIP overexpression inhibits AGE-induced NFκB nuclear translocation, reduced its binding ability with the promoter sequences of the receptor of AGE, consequently inhibiting the translocation of the receptor AGE to the cell membrane for its proper function. Overall, our current study findings suggest that CHIP can target NFκB for ubiquitin-mediated proteasomal degradation, and thereby potentially rescue AGE-induced cardiac damages.

Tanshinone IIA inhibits Leu27IGF-II-induced insulin-like growth factor receptor II signaling and myocardial apoptosis via estrogen receptor-mediated Akt activation.

Different stress condition stimulates the expression level of insulin-like growth factor receptor II (IGF-IIR) in cardiomyoblasts that lead to apoptosis. Tanshinone IIA (TSN), a pharmacologically active component from Danshen, has been shown cardioprotective effects against cardiac apoptosis induced by several stress conditions. Therefore, this study was conducted to assess the cardioprotective effects of TSN IIA mediated through the estrogen receptor (ER) in order to inhibit the Leu27IGF-II-enhanced IGF-IIR-mediated cardiac apoptosis. The estrogenic activity of TSN IIA was examined after myocardial cells were pretreated with the ER antagonist, and inhibited the phospho-inositide-3 kinase (PI3K). Here, we found that TSN IIA significantly induced ER that phosphorylated Akt. Further, Akt activation considerably suppressed the Leu27IGF-II induced IGF-IIR expression level and the downstream effectors, including Gαq and calcineurin as well as mitochondrial dependent apoptosis proteins including Bad, cytochrome c, and active caspase-3 that result in cardiac apoptosis resistance. However, the western blot analysis, JC-1 staining, and terminal deoxynucleotide transferase-mediated dUTP nick end labeling assay revealed that TSN IIA attenuated Leu27IGF-II-induced IGF-IIR mediated cardiac apoptosis was reversed by an ER antagonist such as ICI 182780, and PI3K inhibition. All these findings demonstrate that TSN IIA exerts estrogenic activity, which can activate PI3K-Akt pathway, and thereby inhibits Leu27IGFII induced IGF-IIR mediated cardiac apoptosis. Thus, TSN IIA can be considered as an effective therapeutic strategy against IGF-IIR signaling cascade to suppress cardiac apoptosis.

Prevalence of Overweight and Obesity in People With Severe Mental Illness: Systematic Review and Meta-Analysis.

Aims: 1) To determine the pooled prevalence of overweight and obesity in people with severe mental illness (SMI), overall and by type of SMI, geographical region, and year of data collection; and 2) to assess the likelihood of overweight and obesity, in people with SMI compared with the general population. Methods: PubMed, Medline, EMBASE, and PsycINFO databases were searched to identify observational studies assessing the prevalence of obesity in adults with SMI. Screening, data extraction and risk of bias assessments were performed independently by two co-authors. Random effect estimates for the pooled prevalence of overweight and obesity and the pooled odds of obesity in people with SMI compared with the general population were calculated. Subgroup analyses were conducted for types of SMI, setting, antipsychotic medication, region of the world, country income classification, date of data collection and sex. We assessed publication bias and performed a series of sensitivity analyses, excluding studies with high risk of bias, with low sample size and those not reporting obesity according to WHO classification. Result: 120 studies from 43 countries were included, the majority were from high income countries. The pooled prevalence of obesity in people with SMI was 25.9% (95% C.I. = 23.3-29.1) and the combined pooled prevalence of overweight and obesity was 60.1% (95% C.I. = 55.8-63.1). Sub-Saharan Africa (13.0%, 95%C.I. = 6.7-25.1) and South Asia (17.7%, 95%C.I. = 10.5-28.5) had the lowest prevalence of obesity whilst North Africa and the Middle East (35.8%, 95%C.I. = 23.8-44.8) reported the highest prevalence. People with SMI were 3.04 more likely (95% C.I. = 2.42-3.82) to have obesity than the general population, but there was no difference in the prevalence of overweight. Women with schizophrenia were 1.44 (95% C.I. = 1.25-1.67) times more likely than men with schizophrenia to live with obesity; however, no gender differences were found among those with bipolar disorder. Conclusion: People with SMI have a markedly high prevalence and higher odds of obesity than the general population. This may contribute to the very high prevalence of physical health conditions and mortality in this group. People with SMI around the world would likely benefit from interventions to reduce and prevent obesity.

Inhibition of HDACs Suppresses Cell Proliferation and Cell Migration of Gastric Cancer by Regulating E2F5 Targeting BCL2.

(1) Background: Gastric cancer (GC) is the most common high death-rate cancer type worldwide, with an enhanced prevalence and increased rate of mortality. Although significant evidence on surgery strategy has been generated for the treatment of GC, conclusions are still uncertain regarding profound metastatic or persevering gastric cancer. Therefore, it is essential to develop novel and effective biomarkers or therapeutic targets for the diagnosis of GC. Histone deacetylations (HDACs) are important epigenetic regulators that control the aberrant transcription of critical genes that are mainly involved in cell proliferation, cell migration, regulation of the cell cycle, and different signal pathways. (2) Methods: Expression analysis of HDACs family members and E2F5 in gastric cancer cell lines was determined by RT-PCR and Western blotting. The cell proliferation was determined through an MTT assay. Cell migration was determined using a wound-healing assay. Flow cytometry experiments were used to determine cell-cycle analysis. The statistical software OriginPro 2015 (OriginLab, Northampton, MA, USA) was used to analyze data. A p value of < 0.05 was regarded as significant. (3) Results: The present study shows that E2F5 expression is upregulated in GC cancer cell lines compared to normal cell lines, and is positively associated with the level of HDACs and BCL2. HDACi and knocking down of E2F5 as tumor suppressors inhibited cell proliferation, migration invasion, and blocked the cell cycle in gastric cancer cells by suppressing BCL2. The results conclude that the anticancer mechanism of HDACi was determined by regulating E2F5 via targeting BCL2. (4) Conclusions: Our results suggest that the HDAC-E2F5-BCL2 signaling axis might be a novel potential biomarker in gastric cancer.

E3 ligase activity of Carboxyl terminus of Hsc70 interacting protein (CHIP) in Wharton's jelly derived mesenchymal stem cells improves their persistence under hyperglycemic stress and promotes the prophylactic effects against diabetic cardiac damages.

Recent studies indicate that umbilical cord stem cells are cytoprotective against several disorders. One critical limitation in using stem cells is reduction in their viability under stressful conditions, such as diabetes. However, the molecular intricacies responsible for diabetic conditions are not fully elucidated. In this study, we found that high glucose (HG) conditions induced loss of chaperone homeostasis, stabilized PTEN, triggered the downstream signaling cascade, and induced apoptosis and oxidative stress in Wharton's jelly derived mesenchymal stem cells (WJMSCs). Increased Carboxyl terminus of Hsc70 interacting protein (CHIP) expression promoted phosphatase and tensin homolog (PTEN) degradation via the ubiquitin-proteasome system and shortened its half-life during HG stress. Docking studies confirmed the interaction of CHIP with PTEN and FOXO3a with the Bim promoter region. Further, it was found that the chaperone system is involved in CHIP-mediated PTEN proteasomal degradation. CHIP depletion stabilizes PTEN whereas PTEN inhibition showed an inverse effect. CHIP overactivation suppressed the binding of FOXO3a with bim. Coculturing CHIP overexpressed WJMSCs suppressed HG-induced apoptosis and oxidative stress in embryo derived cardiac cell lines. CHIP overexpressing and PTEN silenced WJMSCs ameliorated diabetic effects in streptozotocin (STZ) induced diabetic rats and further improved their body weight and heart weight, and rescued from hyperglycemia-induced cardiac injury. Considering these, the current study suggests that CHIP confers resistance to apoptosis and acts as a potentiation factor in WJMSCs to provide protection from degenerative effects of diabetes.

CHIP-overexpressing Wharton's jelly-derived mesenchymal stem cells attenuate hyperglycemia-induced oxidative stress-mediated kidney injuries in diabetic rats.

Accumulating studies have demonstrated the protective roles of mesenchymal stem cells against several disorders. However, one of their crucial limitations is reduced viability under stress conditions, including the hyperglycemia induced by diabetes. The molecular mechanisms involved in diabetes-induced kidney injuries are not fully elucidated. In this study, we found that high glucose (HG) reduced human proximal tubular epithelial cell viability. Further, hyperglycemia induced oxidative stress-mediated apoptosis and fibrosis in HK-2 cells via activation of the mitogen-activated protein kinases (MAPKs) including c-Jun N-terminal kinase JNK and p38 kinase. Carboxyl terminus of HSP70 interacting protein (CHIP) overactivation considerably rescued cell viability under HG stress. Moreover, Western blot analysis, flow cytometry, and MitoSOX staining revealed that hyperglycemia-induced mitochondrial oxidative stress production and apoptosis were attenuated in CHIP-overexpressing Wharton's jelly-derived mesenchymal stem cells (WJMSCs). Co-culture with CHIP-expressing WJMSCs maintained HK-2 cell viability, and inhibited apoptosis and fibrosis by attenuating HG-induced ROS-mediated MAPK activation. CHIP-overexpressing WJMSCs also rescued the decreased kidney weight and hyperglycemia-induced kidney damage observed in streptozotocin-induced diabetic rats. Cumulatively, the current research findings demonstrate that CHIP suppresses hyperglycemia-induced oxidative stress and confers resistance to MAPK-induced apoptosis and fibrosis, and suggests that CHIP protects WJMSCs and the high quality WJMSCs have therapeutic effects against diabetes-induced kidney injuries.

Unusual magnetotransport properties in graphene fibers.

Graphene, purely sp2-hybridized, has already been extensively studied for magnetoelectronics, however, the magnetotransport properties of graphene fibers (GrFib) have not been explored very well to date. Herein, unique magnetotransport properties of graphene fibers are detected. All the GrFib-samples show the highest positive magnetoresistance (MR ∼ 60%) at room temperature (300 K) that gradually decreases (MR ∼ 37%) at low temperature (5 K), indicating quite different behavior for a graphene derivative. The MR of three different morphologies are compared: single graphene sheet (60-100% at 300 K and 100-110% at 5 K under an applied magnetic field of 5 T), graphene foam (GF-100% at 300 K and 158% at 5 K under an applied magnetic field of 5 T), and graphene fiber (60% at 300 K and 37% at 300 K under an applied magnetic field of 5 T), and found that each morphology has a different magnitude of MR under similar magnitude of magnetic field and temperature. Unlike graphene and GF, GrFib shows a decreasing trend of MR at low temperatures, violating commonly used weak anti-localization phenomena in graphene. Technologically, each morphology of graphene has a unique set of magnetotransport properties that can be considered for particular magnetoelectronic devices depending upon the mechanical, electrical, and magnetotransport properties.

Efficacy and safety of Suprachoroidal Triamcinolone Acetonide in cases of resistant diabetic Macular Edema.

OBJECTIVE: To evaluate the safety and efficacy of Suprachoroidal Triamcinolone Acetonide (SCTA) injection in patients with treatment resistant Diabetic Macular Edema (DME). METHODS: This was a prospective non randomized interventional study conducted in the vitreoretinal department of Al Ehsan Welfare Eye Hospital, Lahore, Pakistan from March 2018 to September 2018. A total of 24 eyes of 24 patients were included. Baseline Best Corrected Visual Acuity (BCVA), Intra Ocular Pressure (IOP) and Central Subfield Thickness (CST) was recorded. After SCTA, patient was followed up at one and three months and same clinical parameters were recorded again and results analyzed. RESULTS: Out of 24 patients, 11(45.83%) were males and 13(54.16%) were females. Mean pre injection CST was 636.5 ± 200.11 um. Mean pre injection BCVA was 0.8 ± 0.24 on ETDRS chart. Mean post injection CST at one and three months was 304.54 ± 67.43 and 302.66 ± 66.93 um. Mean post injection BCVA at one and three months was 0.47 ± 0.3 and 0.45 ± 0.27 on ETDRS chart. The results were statistically significant for pre and post injection CST at both one and three months (p-value < 0.00001). Pre and post injection BCVA was also statistically significant (p-value < 0.05). CONCLUSION: Preliminary evidence suggests that SCTA is well tolerated and may help in improving functional and structural outcomes of treatment resistant DME.