Dopamine D1- and D2-like receptors oppositely regulate lifespan via a dietary restriction mechanism in Caenorhabditis elegans.

BACKGROUND: Despite recent progress in understanding the molecular mechanisms regulating aging and lifespan, and the pathways involved being conserved in different species, a full understanding of the aging process has not been reached. In particular, increasing evidence suggests an active role for the nervous system in lifespan regulation, with sensory neurons, as well as serotonin and GABA signaling, having been shown to regulate lifespan in Caenorhabditis elegans (C. elegans). However, the contribution of additional neural factors, and a broad understanding of the role of the nervous system in regulating aging remains to be established. Here, we examine the impact of the dopamine system in regulating aging in C. elegans. RESULTS: We report that mutations of DOP-4, a dopamine D1-like receptor (D1R), and DOP-2, a dopamine D2-like receptor (D2R) oppositely affected lifespan, fast body movement span, reproductive lifespan, and developmental rate in C. elegans. Activation of D2R using aripiprazole, an antipsychotic drug, robustly extended both lifespan and healthspan. Conversely, inhibition of D2R using quetiapine shortened worm lifespan, further supporting the role of dopamine receptors in lifespan regulation. Mechanistically, D2R signaling regulates lifespan through a dietary restriction mechanism mediated by the AAK-2-DAF-16 pathway. The DAG-PKC/PKD pathway links signaling between dopamine receptors and the downstream AAK-2-DAF-16 pathway to transmit longevity signals. CONCLUSIONS: These data demonstrated a novel role of dopamine receptors in lifespan and dietary restriction regulation. The clinically approved antipsychotic aripiprazole holds potential as a novel anti-aging drug.

Quetiapine Shortens the Lifespan of Caenorhabditis elegans through DOP-2, DAF-2 and RSKS-1.

Recent studies implicate a key role of dopamine signaling in lifespan regulation. Our previous study found that quetiapine, an atypical antipsychotic drug that has antagonistic activity on dopamine D2-like receptors (D2Rs), shortened the lifespan of Caenorhabditis elegans (C. elegans). However, the detailed mechanism of this effect was not clear. In the present study, we evaluate the effect of quetiapine on aging and explore its underlying molecular mechanism. The results show that quetiapine shortened healthspan in C. elegans. The lifespan-shortening effect is dependent on DOP-2, a D2R expressed in worms. Quetiapine shortens lifespan through the C. elegans insulin and IGF-1 receptor DAF-2, but not the downstream Akt pathway. Quetiapine-induced lifespan reduction is dependent on RSKS-1, a key protein kinase that functions in mTOR signaling. In addition, the quetiapine effect is also related to mitochondrial function. These findings further support the key role of dopamine signaling in lifespan regulation and promote our insight into the mechanism of action of antipsychotic drugs.

Pharmacological Treatment of Alzheimer's Disease: Insights from Drosophila melanogaster.

Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer's disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular ß-amyloid (Aß) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD.

Metformin protects PC12 cells and hippocampal neurons from H2 O 2 -induced oxidative damage through activation of AMPK pathway.

Metformin, a first line anti type 2 diabetes drug, has recently been shown to extend lifespan in various species, and therefore, became the first antiaging drug in clinical trial. Oxidative stress due to excess reactive oxygen species (ROS) is considered to be an important factor in aging and related disease, such as Alzheimer's disease (AD). However, the antioxidative effects of metformin and its underlying mechanisms in neuronal cells is not known. In the present study, we showed that metformin, in clinically relevant concentrations, protected neuronal PC12 cells from H2 O2 -induced cell death. Metformin significantly ameliorated cell death due to H2 O2 insult by restoring abnormal changes in nuclear morphology, intracellular ROS, lactate dehydrogenase, and mitochondrial membrane potential induced by H2 O2 . Hoechst staining assay and flow cytometry analysis revealed that metformin significantly reduced the apoptosis in PC12 cells exposed to H2 O2 . Western blot analysis further demonstrated that metformin stimulated the phosphorylation and activation of AMP-activated protein kinase (AMPK) in PC12 cells, while application of AMPK inhibitor compound C, or knockdown of the expression of AMPK by specific small interfering RNA or short hairpin RNA blocked the protective effect of metformin. Similar results were obtained in primary cultured hippocampal neurons. Taken together, these results indicated that metformin is able to protect neuronal cells from oxidative injury, at least in part, via the activation of AMPK. As metformin is comparatively cheaper with much less side effects in clinic, our findings support its potential to be a drug for prevention and treatment of aging and aging-related diseases.

Population genomics identifies patterns of genetic diversity and selection in chicken.

BACKGROUND: There are hundreds of phenotypically distinguishable domestic chicken breeds or lines with highly specialized traits worldwide, which provide a unique opportunity to illustrate how selection shapes patterns of genetic variation. There are many local chicken breeds in China. RESULTS: Here, we provide a population genome landscape of genetic variations in 86 domestic chickens representing 10 phenotypically diverse breeds. Genome-wide analysis indicated that sex chromosomes have less genetic diversity and are under stronger selection than autosomes during domestication and local adaptation. We found an evidence of admixture between Tibetan chickens and other domestic population. We further identified strong signatures of selection affecting genomic regions that harbor genes underlying economic traits (typically related to feathers, skin color, growth, reproduction and aggressiveness) and local adaptation (to high altitude). By comparing the genomes of the Tibetan and lowland fowls, we identified genes associated with high-altitude adaptation in Tibetan chickens were mainly involved in energy metabolism, body size maintenance and available food sources. CONCLUSIONS: The work provides crucial insights into the distinct evolutionary scenarios occurring under artificial selection for agricultural production and under natural selection for success at high altitudes in chicken. Several genes were identified as candidates for chicken economic traits and other phenotypic traits.

Genetic diversity and natural selection in wild fruit flies revealed by whole-genome resequencing.

We characterized 26 wild fruit flies comparative population genomics from six different altitude and latitude locations by whole genome resequencing. Genetic diversity was relatively higher in Ganzi and Chongqing populations. We also found 13 genes showing selection signature between different altitude flies and variants related to hypoxia and temperature stimulus, were preferentially selected during the flies evolution. One of the most striking selective sweeps found in all high altitude flies occurred in the region harboring Hsp70Aa and Hsp70Ab on chromosome 3R. Interestingly, these two genes are involved in GO terms including response to hypoxia, unfolded protein, temperature stimulus, heat, oxygen levels. Mutation in HPH gene, a candidate gene in the hypoxia inducible factor pathway, might contributes to hypoxic high-altitude adaptation. Intriguingly, some of the selected genes, primarily utilized in humans, were involved in the response to hypoxia, which could imply a conserved molecular mechanisms underlying high-altitude adaptation between insects and humans.

14-3-3 Proteins Are on the Crossroads of Cancer, Aging, and Age-Related Neurodegenerative Disease.

14-3-3 proteins are a family of conserved regulatory adaptor molecules which are expressed in all eukaryotic cells. These proteins participate in a variety of intracellular processes by recognizing specific phosphorylation motifs and interacting with hundreds of target proteins. Also, 14-3-3 proteins act as molecular chaperones, preventing the aggregation of unfolded proteins under conditions of cellular stress. Furthermore, 14-3-3 proteins have been shown to have similar expression patterns in tumors, aging, and neurodegenerative diseases. Therefore, we put forward the idea that the adaptor activity and chaperone-like activity of 14-3-3 proteins might play a substantial role in the above-mentioned conditions. Interestingly, 14-3-3 proteins are considered to be standing at the crossroads of cancer, aging, and age-related neurodegenerative diseases. There are great possibilities to improve the above-mentioned diseases and conditions through intervention in the activity of the 14-3-3 protein family.

Artemisinin Attenuated Hydrogen Peroxide (H2O2)-Induced Oxidative Injury in SH-SY5Y and Hippocampal Neurons via the Activation of AMPK Pathway.

Oxidative stress is believed to be one of the main causes of neurodegenerative diseases such as Alzheimer's disease (AD). The pathogenesis of AD is still not elucidated clearly but oxidative stress is one of the key hypotheses. Here, we found that artemisinin, an anti-malarial Chinese medicine, possesses neuroprotective effects. However, the antioxidative effects of artemisinin remain to be explored. In this study, we found that artemisinin rescued SH-SY5Y and hippocampal neuronal cells from hydrogen peroxide (H2O2)-induced cell death at clinically relevant doses in a concentration-dependent manner. Further studies showed that artemisinin significantly restored the nuclear morphology, improved the abnormal changes in intracellular reactive oxygen species (ROS), reduced the mitochondrial membrane potential, and caspase-3 activation, thereby attenuating apoptosis. Artemisinin also stimulated the phosphorylation of the adenosine monophosphate -activated protein kinase (AMPK) pathway in SH-SY5Y cells in a time- and concentration-dependent manner. Inhibition of the AMPK pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells. Similar results were obtained in primary cultured hippocampal neurons. Cumulatively, these results indicated that artemisinin protected neuronal cells from oxidative damage, at least in part through the activation of AMPK. Our findings support the role of artemisinin as a potential therapeutic agent for neurodegenerative diseases.

Gene expression patterns determine the differential numbers of dorsocentral macrochaetes between Musca domestica and Drosophila melanogaster.

The evolutionary differences in sensory bristle patterns on the thorax of dipterans are an excellent model for studying the patterns of evolutionary development. We observed that Drosophila melanogaster has two pairs of the large bristles, called macrochaetes, in the dorsocentral (DC) region of the notum, while Musca domestica retains six DC macrochaetes. To explore possible mechanism by which these two dipteran species have different numbers of DC bristles, we compared the corresponding protein sequences, the gene expression levels and the spatial expression patterns of five genes (scute, pnr, ush, hairy, and emc) for bristle development between two species. We also checked the overexpression of scute and emc in transgenic flies. The results demonstrated a strong conservation of five protein sequences between these two species. The mRNA expression of the five genes differed significantly between D. melanogaster and M. domestica. The gene expression patterns exhibited a species-specific pattern during the larval development stage. It suggests that the function of these genes has been conserved in regulating the development of macrocheates between housefly and fruit fly, whereas the gene expression levels, especially spatial expression patterns lead to species-specificity in DC bristles.

DNA methylation is not involved in dietary restriction induced lifespan extension in adult Drosophila.

Dietary restriction (DR) is widely regarded as a viable intervention to extend lifespan and healthspan in diverse organisms. The precise molecular regulatory mechanisms are largely unknown. Epigenetic modifications are not stable upon DR and also keep changing with age. Here, we employed whole genome bisulfite sequencing to determine the DNA methylation changes upon DR in adult Drosophila. Our results indicate that although a low level of DNA methylation exists in the adult Drosophila genome, there is no significant difference in DNA methylation levels upon DR when compared to unrestricted flies. This suggests that other epigenetic components such as histone modifications might be altered by DR.

Intestinal Homeostasis and Longevity: Drosophila Gut Feeling.

The association between intestinal homeostasis and life span has caught the attention of the research community worldwide. There have been multiple evidences which support the role of gut homeostasis in aging. The Drosophila gastrointestinal tract is very similar to the mammalian gut, and therefore it can directly be used as a model to understand the association between gut microbiota, immune system, and aging in humans. In current review we have discussed the importance of gut microbiota in aging. Also we have highlighted the importance of host immune system and gut aging. Since the increased microbial load in the gut activates the host immune system, the dysregulated microbiota can have direct implications in gut aging. The proliferation and renewal of intestinal stem cells can also affect gut aging. Another important aspect that we have discussed is the communication between the gut and the other organ systems which affect the overall aging process. Altogether we propose that the Drosophila gut can be a good model to improve our understanding of human gut aging.

Berberine Protects Human Retinal Pigment Epithelial Cells from Hydrogen Peroxide-Induced Oxidative Damage through Activation of AMPK.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the elderly with less effective treatment, especially for dry AMD (90% of AMD). Although the etiology of this disease is not well elucidated, increasing evidences indicate that excessive reactive oxygen species (ROS) impairing the physiological functions of retinal pigment epithelium (RPE) cells may be one of the main causes. Therefore, it could be a great strategy to find some drugs that can effectively protect RPE cells from oxidative damage which is desired to treat and slow the process of AMD. In the present study, a well-known traditional Chinese medicine berberine (BBR) was found to suppress hydrogen peroxide (H2O2)-induced oxidative damage in D407 cells, a human RPE cell line. Pre-treatment of D407 cells with BBR significantly suppressed H2O2-induced cell apoptosis by restoring abnormal changes in nuclear morphology, preventing the decline of mitochondrial membrane potential, reducing lactate dehydrogenase release and inhibiting caspase 3/7 activities induced by H2O2. Western blot analysis showed that BBR was able to stimulate the phosphorylation/activation of AMPK in a time- and dose-dependent manner in D407 cells, while treatment of cells with AMPK pathway inhibitor Compound C, or knockdown of the AMPK by specific siRNA blocked the effect of BBR. Similar results were obtained in primary cultured human RPE cells. Taken together, these results demonstrated that BBR was able to protect RPE cells against oxidative stress via the activation of AMPK pathway. Our findings also indicate the potential application of BBR in AMD treatment.

Tanshinone IIA Attenuates Insulin Like Growth Factor 1 -Induced Cell Proliferation in PC12 Cells through the PI3K/Akt and MEK/ERK Pathways.

The insulin like growth factor 1 (IGF-1) and its receptor (IGF-1R) facilitate tumor proliferation and progression. Tanshinone IIA (TSN) is an active diterpene quinone isolated from the roots of the herbal plant Salvia miltiorrhiza. TSN inhibits the proliferation of various types of cancer cells but its role in the IGF-1R-induced proliferation of pheochromocytoma (PC12) cells and the potential mechanisms are largely unknown. This study aims to investigate the anti-proliferative effect of TSN in PC12 cells and its role on IGF-1R signaling transduction. PC12 cells were treated with IGF-1 with or without TSN, methyl thiazolytetrazolium (MTT) assay, and cell counting kit-8 and flow cytometry were used to evaluate the proliferation of PC12 cells. The role of TSN on the apoptosis of PC12 cells were detected by flow cytometry as well. The effects of TSN and IGF-1 on the phosphorylation of IGF-1R, protein kinase B (Akt), extracellular-signal related kinase 1/2 (ERK1/2) and other downstream targets were analyzed by Western blotting analysis. Our results showed that IGF-1 promoted the growth of PC12 cells in a dose-dependent manner and increased the phosphorylation of IGF-1R, whereas TSN attenuated the effect of IGF-1. Interestingly, TSN did not induce cell apoptosis in PC12 cells. Moreover, TSN attenuated the phosphorylation of Akt and ERK1/2 induced by IGF-1, and the phosphorylation of glycogen synthase kinase-3ß, forkhead box O3a (FOXO3a) and c-Raf were also inhibited by TSN. Furthermore, TSN inhibited cell growth induced by IGF-1 and blocked the activation of IGF-1R in SH-SY5Y cells. Taken together, TSN has an inhibitory effect on the proliferation of PC12 cells via down-regulation of the phosphorylated IGF-1R and its downstream signaling.

Knowledge, Attitudes, and Practices of Hand Hygiene, Mask Use, and Social Distancing among Public Hospital and Polyclinic Nurses in Barbados during the Coronavirus 2019 Pandemic.

BACKGROUND: Nurses are essential members of the healthcare workforce and were among the first-line carers for patients in community and hospital settings during the COVID-19 pandemic. As a result, they were at a heightened risk of infection, resulting in several reported deaths among nursing staff. Several preventive measures were adopted to contain the spread of the COVID-19 virus. This study aims to explore the knowledge, attitudes, and practices (KAP) of nurses regarding hand hygiene, mask wearing, and social distancing measures in healthcare settings in Barbados during the COVID-19 pandemic. METHOD: An online survey of nurses working in public hospitals and polyclinics (public primary care clinics) in Barbados from March 2021 to December 2021 was conducted. A nonsystematic convenience sampling method was employed to recruit nurses who were readily available and willing to participate. A questionnaire captured the sociodemographic information and knowledge and practices related to hand hygiene, the use of face masks, and social distancing. Each correct response received one mark. Overall knowledge scores were categorized as poor (<60%), average (60-80%), or good (>80-100%). RESULTS: Of the 192 participants, the majority were female (82.8%) and had >5 years of experience (82%). The findings revealed that 45.8% had poor knowledge of hand hygiene, and that the knowledge of 43.8% of respondents was average. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 2.1 times increased odds (95% confidence interval 1.0, 4.2) of having good knowledge compared to other nursing categories. Regarding mask wearing, 53.6% of nurses had average knowledge, and 27.1% had good knowledge. Multivariable logistic regression showed that, after adjustment for age and gender, registered nurses had 3.3 times increased odds (95% confidence interval 1.5, 7.4) of having good knowledge compared to nursing assistants. A total of 68.6% of respondents followed the correct steps of handwashing every time, and 98.3% wore a mask in public places. More than half of the nurses (51.2%) kept a safe distance from others to avoid spreading SARS-CoV-2; one-third were in a crowded place(s) in the past three months, and 55.8% usually followed guidelines for social isolation as recommended by the WHO. CONCLUSIONS: The study identified knowledge deficiencies related to hand hygiene and wearing masks among nurses. It is imperative to provide additional training on infection control measures.

Self-reported side effects of COVID-19 vaccines among health professions students in India.

Studies focusing on the safety and common side effects of vaccines play a crucial role in enhancing public acceptance of vaccination. Research is scarce regarding the usage of COVID-19 vaccines and the side effects experienced by health professions students in India and other countries. This study aimed to document self-reported side effects associated with COVID-19 vaccination among medical and dental students of six medical and dental colleges and teaching hospitals in four states (Tamil Nadu, Madhya Pradesh, Gujarat, and West Bengal) of India. A cross-sectional survey using purposive sampling of medical and dental students was conducted from 26 April to 26 May 2021. Data was collected using a Google Forms questionnaire capturing information regarding receiving COVID-19 vaccines, side effects and symptoms, onset and duration of symptoms, use of treatment to alleviate symptoms, awareness of haematologic risks associated with vaccination, and side effects from previous (non-COVID-19) vaccinations. The majority (94.5%) of participants received both doses of the Covishield/AstraZeneca COVID-19 vaccine. Among participants (n = 492), 45.3% (n = 223) reported one or more side effects. The most frequently reported side effects were soreness of the injected arm (80.3%), tiredness (78.5%), fever (71.3%), headache (64.1%), and hypersomnia (58.7%). The two most common severe symptoms were fever (14.8%) and headache (13%). Most side effects appeared on the day of vaccination: soreness of the injection site (57%), fever (43.1%), and tiredness (42.6%). Most reported symptoms persisted for one to three days-soreness of the injection site (53%), fever (47.1%), and headache (42.6%). Logistic regression showed that women were almost 85% less likely to report side effects. The study's findings corroborate the safety of the Covishield/AstraZeneca vaccine's first dose, evidenced by the relatively minor and transient nature of the side effects. However, the study underscores the necessity for ongoing research to assess the long-term impacts of COVID-19 vaccines, especially in the context of booster doses, thereby contributing to the global understanding of vaccine safety and efficacy.

Evaluation of Short-Term Side Effects Following the First Dose of COVID-19 Vaccines Among Physicians and Dentists: A Cross-Sectional Study from India.

Background: Efficacy and safety are fundamental for the development of successful COVID-19 vaccines. Vaccine-associated side effects influence vaccine hesitancy. This study investigated the prevalence, severity, and onset of side effects following the first dose of COVID-19 vaccines among physicians and dentists working in various healthcare settings across India. Methods: A cross-sectional survey collected self-report data from April to June 2021 on side effects following the first dose of the vaccine. An online validated questionnaire using the Google Docs® platform was circulated via email and social media platforms. Results: More than 40% of participants experienced at least one side effect after the first dose of vaccination; the most common were mild and resolved within three days after vaccination. More than 91% of respondents received the Covishield (AstraZeneca) vaccine; the most prevalent adverse effects were soreness of the injected arm (78.9%), tiredness (71.1%), and fever (54.9%). Logistic regression showed that women were almost 60% less likely to report side effects. Conclusion: Findings supported the safety of the first dose of the COVID-19 vaccine based on relatively few self-limiting side effects, mainly soreness of the injected arm and tiredness. Further research is needed to determine the long-term safety of COVID-19 vaccines, especially after booster doses.

Inhibitor GSK690693 extends Drosophila lifespan via reduce AKT signaling pathway.

Aging is a process involving physiological changes that lead to the decline of biological functions of various tissues and organs of the body. Therefore, it is crucial to find anti-aging drugs that can intervene with the changes induced because of aging and slow down the degeneration of the biological functions. Among many signaling pathways linked with aging and aging-related diseases, PI3K-AKT signaling pathway has attracted major attention in aging biology. In this research paper, we have demonstrated that AKT inhibitor GSK690693 can extend lifespan in Drosophila irrespective of start of the treatment from the beginning of life or the mid-life. Effect of GSK690693 for lifespan extension has been primarily related to the improvements in oxidative resistance, intestinal integrity and increased autophagy, but not in physical activity or starvation resistance. Furthermore, GSK690693 treatment reduced the activation of AKT and ERK, consequently activating FOXO, GSK-3ß and apoptosis to modulate longevity of flies. Remarkably, GSK690693 did not induce hyperglycemia after treatment. The results indicate that GSK690693 may become an effective compound for anti-aging intervention.

Impact of COVID-19 pandemic on radiology education, training, and practice: A narrative review.

Radiology education and training is of paramount clinical importance given the prominence of medical imaging utilization in effective clinical practice. The incorporation of basic radiology in the medical curriculum has continued to evolve, focusing on teaching image interpretation skills, the appropriate ordering of radiological investigations, judicious use of ionizing radiation, and providing exposure to interventional radiology. Advancements in radiology have been driven by the digital revolution, which has, in turn, had a positive impact on radiology education and training. Upon the advent of the corona virus disease 2019 (COVID-19) pandemic, many training institutions and hospitals adhered to directives which advised rescheduling of non-urgent outpatient appointments. This inevitably impacted the workflow of the radiology department, which resulted in the reduction of clinical in-person case reviews and consultations, as well as in-person teaching sessions. Several medical schools and research centers completely suspended face-to-face academic activity. This led to challenges for medical teachers to complete the radiology syllabus while ensuring that teaching activities continued safely and effectively. As a result, online teaching platforms have virtually replaced didactic face-to-face lectures. Radiology educators also sought other strategies to incorporate interactive teaching sessions while adopting the e-learning approach, as they were cognizant of the limitations that this may have on students' clinical expertise. Migration to online methods to review live cases, journal clubs, simulation-based training, clinical interaction, and radiology examination protocolling are a few examples of successfully addressing the limitations in reduced clinical exposure. In this review paper, we discuss (1) The impact of the COVID-19 pandemic on radiology education, training, and practice; (2) Challenges and strategies involved in delivering online radiology education for undergraduates and postgraduates during the COVID-19 pandemic; and (3) Difference between the implementation of radiology education during the COVID-19 pandemic and pre-COVID-19 era.

Artemisinin Improved Neuronal Functions in Alzheimer's Disease Animal Model 3xtg Mice and Neuronal Cells via Stimulating the ERK/CREB Signaling Pathway.

The most common form of dementia is Alzheimer's disease which is characterized by memory loss and cognitive disorders. The pathogenesis of Alzheimer's disease is not known at present but toxicity of amyloid-beta is one of the central hypotheses. Amyloid-beta can stimulate the production of reactive oxygen species (ROS), cause oxidative stress, damage mitochondrial, cause inflammatory reactions and activate apoptosis related factors which lead to the neuronal death. In this study, we found that artemisinin, a first line antimalarial drug used in clinic for decades, improved the cognitive functions in Alzheimer's disease animal model 3xTg mice. Further study showed that artemisinin reduced the deposition of amyloid-beta and tau protein, reduced the release of inflammation factors and apoptosis factors, and thereby reduced the neuronal cell death. Western blot assay showed that artemisinin stimulated the activation of ERK/CREB signaling pathway. Consistent with these results, artemisinin concentration-dependently promoted the survival of SH-SY5Y cell against toxicity of amyloid-beta protein 1-42 induced ROS accumulation, caspase activation and apoptosis. Artemisinin also stimulated the phosphorylation of ERK1/2 and CREB in SH-SY5Y cells in time and concentration-dependent manner. Inhibition of ERK/CREB pathway attenuated the protective effect of artemisinin. These data put together suggested that artemisinin has the potential to protect neuronal cells in vitro as well as in vivo animal model 3xTg mice via, at least in part, the activation of the ERK/CREB pathway. Our findings also strongly support the potential of artemisinin as a new multi-target drug that can be used for preventing and treating the Alzheimer's disease.

Keloids: Current and emerging therapies.

Keloids are pathological scars that grow over time and extend beyond the initial site of injury after impaired wound healing. These scars frequently recur and rarely regress. They are aesthetically disfiguring, can cause pain, itching, discomfort as well as psychological stress, often affecting quality of life. Many treatment modalities, including surgical and non-surgical, have been explored and have been reported to be beneficial; however, none have been absolutely satisfactory or optimal for the treatment of all keloid subtypes to date. This poses a major challenge to clinicians. Often, a combinational therapeutic approach appears to offer the best results with higher patient satisfaction compared to monotherapy. The aetiopathogenesis of keloids is not fully elucidated; however, with recent advances in molecular biology and genetics, insight is being gained on the complex process of scar formation and hence new therapeutic and management options for keloids. In this paper, we explore the literature and summarise the general concepts surrounding keloid development and review both current (corticosteroids, surgical excision, silicone-based products, pressure therapy, radiotherapy, cryotherapy, laser therapy, imiquimod and 5-fluorouracil) and emerging (stem cell therapy, mitomycin C, verapamil, interferons, bleomycin, botulinum toxin type A and angiotensin-converting enzyme inhibitors) treatments. Increased knowledge and understanding in this area may potentially lead to the discovery and development of novel therapeutic options that are more efficacious for all keloid types. LAY SUMMARY: Keloids are problematic scars that are difficult to treat and manage. The aetiopathogenesis of keloids is not clear; however, recent advances in molecular biology and genetics are beginning to shed light on the underlying mechanisms implicated in keloid scar formation which will hopefully lead to the development of treatment options for all keloid types. This review summarises current and emerging therapies.