Biofabrication and biomanufacturing are rapidly transforming how materials,therapeutics,and functional biological constructs are produced.These fields integrate developments in sustainable biomaterials,precision fabri...Biofabrication and biomanufacturing are rapidly transforming how materials,therapeutics,and functional biological constructs are produced.These fields integrate developments in sustainable biomaterials,precision fabrication,biological systems,and data-driven engineering to produce scalable,efficient,and environmentally aligned production pathways.This review highlights recent scientific advances led by researchers in Singapore,focusing on three interconnected pillars:sustainable bio derived materials,enabling fabrication and manufacturing technologies,and emerging applications.We first examine the expanding use of biomass-derived feedstocks,including human hair keratin,aquaculture side-streams,and plant-derived polysaccharides,which support circular and resource-conscious material development.We then present advances in biofabrication technologies,including electrospinning,three-dimensional bioprinting,and metal additive manufacturing,that enable improved control over the structure,function,and manufacturability of biomedical and functional constructs.Emerging applications,such as machine learning-assisted additive manufacturing,food biomanufacturing,regenerative cell therapy,microneedles,and bioelectronics,exemplify how biofabrication and biomanufacturing are increasingly interrelated across the health,materials,and technological domains.These research contributions from Singapore exemplify how sustainable feedstocks,digital and automated fabrication platforms,and biologically driven applications are shaping the evolving landscape of biofabrication and biomanufacturing.The convergence of materials science,biological engineering,and advanced manufacturing continues to enable new opportunities for innovation in biomedical,industrial,and societal contexts.展开更多
Many studies on aging have focused on evaluating differences between older and younger people, but only a few have focused on differences in skin properties among subjects from the same age group according to their sk...Many studies on aging have focused on evaluating differences between older and younger people, but only a few have focused on differences in skin properties among subjects from the same age group according to their skin aging status. In this study, we evaluated the facial skin condition and life style factors in 110 Korean women aged 25 to 35 in an attempt to evaluate factors which may affect the skin aging status in the initial aging phase. The facial skin condition of 110 healthy Korean women was assessed over two successive 6-month periods, summer and winter. Using clinical assessments including aging, wrinkles and skin’s elasticity values, the subjects were divided into 7 groups. Then, various facial skin conditions and life style factors were examined between a severe aging group and mild aging group. In the severe aging group, the mean value pH was lower and the mean value of water content was slightly lower than that of women in the mild aging group. Also, the seasonal site variation in water content and sebum secretion level were significantly higher in the severe aging group than in the mild aging group. Topical sunscreen using percentage was not significantly different between the two groups. However, the number of cosmetic subject use was slightly higher in the mild aging group than in the severe aging group. The study suggested that there were several differences in skin characteristics between women in the severe aging group and in the mild aging group at the initial aging phase. Seasonal site variation between cheek and forehead was the most dominant differences. We also considered that life style factors such as cosmetic use could affect skin aging status.展开更多
OBJECTIVES: Skin characteristics change depending on the external environment such as UV, temperature and humidity. But the research how to affect the regional climate, age and seasonal variation on the skin condition...OBJECTIVES: Skin characteristics change depending on the external environment such as UV, temperature and humidity. But the research how to affect the regional climate, age and seasonal variation on the skin conditions was not well studied. Therefore, we investigated the seasonal variation in the skin by comparing Beijing women and Guangzhou women by age groups. METHODS: 440 healthy Chinese women participated in this study. The skin hydration, sebum secretion, TEWL and skin pH were measured on the cheek front. All the parameters were analyzed in terms of the age, season and region. RESULTS: The skin hydration in Beijing was lower than that in Guangzhou and significantly decreased during winter than summer. The sebum secretion in their 20s and 30s was significantly high in summer in both regions, and this phenomenon was more remarkable in Guangzhou (p CONCLUSIONS: Skin hydration and barrier function decreased more during a cold, dry winter than summer. The barrier dysfunctions such as an increase in TEWL and pH occurred more commonly in old age groups. The greater the differences between summer and winter climates, the greater damage to skin barrier and skin hydration. The sebum secretion was more affected by hot, humid summers. Further, the aged skin was influenced by seasonal variation except for sebum secretion.展开更多
Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy, which causes substantial morbidities and mortalities. Although the significant increase in the understanding of skin cancer...Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy, which causes substantial morbidities and mortalities. Although the significant increase in the understanding of skin cancer formation and the development of novel personalized drug regimens have occurred, new treatment options are always of need. The use of natural compounds to alleviate the symptoms or even to prevent and treat cancer has long been proposed. Specifically, the use of marine-based organisms as a source for cancer cure and remedy is being evaluated extensively. The objective of the current study was to assess the ability of the green microalgae Dunaliella salina, the Dead-Sea-derived Haloferax volcanii, and its combinations to treat skin cancer in vitro. The results demonstrate the Dunaliella and Haloferax can reduce sarcoma and basal cell carcinoma cellular growth. Importantly, their combination acts synergistically in a caspase-3 independent manner. Moreover, a synergistic action was found when evaluated sarcoma cell invasion rate, which was completely blocked at pharmacological relevant amounts of the compounds. Collectively, the results demonstrate that the combination of Haloferax volcanii and Dunaliella salina can be used as a new treatment for skin cancer. The specific mechanism of action and further in vivo validation studies are of need.展开更多
Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance ofskin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring e...Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance ofskin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, andthe repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the contextof understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers thesubsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstreamsignaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectivelyinfluence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improvingskin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.展开更多
<strong>Background:</strong> Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite <span>its efficacy, the ...<strong>Background:</strong> Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite <span>its efficacy, the safety profile of RE is controversial. <b>Objectives:</b> Pretinol (PRE) complex was formulated with two RE precursors, <i>β</i>-Carotene and Niacinamide,</span><span> </span>in order to deliver retinol-like skin benefits with healthier characteristics, as<span>suming that skin enzymes will enable safe RE supply on spot. <b>Methods:</b> The expres</span><span>sion levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNF<i>α</i>) and In</span><span>terleukin 1 alpha (IL-1<i>α</i>), were measured using various skin models before and</span><span> </span><span>after exposure to PRE and RE. Full genome microarray was performed and the</span> <span>affected genes and pathways were analyzed. <b>Results:</b> Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated</span><span>.</span><span> </span><span>Skin safety, demonstrated via cytokines expression on <i>ex-vivo</i> skin, results with TNF<i>α</i> and IL-1<i>α</i> elevation by RE application. In contrary PRE significantly reduces</span> TNF<i>α</i> while IL-1<i>α</i> is not affected. These results establish skin safety advantage of PRE <i>vs</i> RE. Microarray results examined on skin equivalents reveal <span>the involvement of PRE in inflammatory attenuation. <b>Conclusions:</b> Formulat</span>ing RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.展开更多
Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this ...Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.展开更多
BACKGROUND Facial cosmetic procedures become popular for people with a desire to have a younger appearance,and cosmetic technology has developed rapidly over the past several decades.However,increasing complications r...BACKGROUND Facial cosmetic procedures become popular for people with a desire to have a younger appearance,and cosmetic technology has developed rapidly over the past several decades.However,increasing complications related to cosmetic injections have been reported,and infection is one of the most serious problems and can cause anxiety and facial injury.We here report a case of Majocchi’s granuloma(MG)caused by Trichophyton rubrum after facial injection of hyaluronic acid.CASE SUMMARY A 37-year-old woman presented to our hospital with a history of red papules,nodules,and abscesses on her left zygomatic arch for 2 mo.She had received a cosmetic injection of hyaluronic acid on the left side of her face prior to the appearance of the lesions.MG caused by Trichophyton rubrum after facial injection of hyaluronic acid was diagnosed based on morphology and molecular biological identification.In vitro antifungal susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute M38-A2 method.Minimal inhibitory concentrations were used to evaluate the antifungal susceptibility.The antifungal agents and their minimal inhibitory concentrations for the strain were terbinafine(<0.5μg/mL),itraconazole(0.06μg/mL),amphotericin B(0.25μg/mL),fluconazole(32μg/mL),voriconazole(0.125μg/mL),posaconazole(0.125μg/mL),and isavuconazole(0.06μg/mL).We initially administered 250 mg/d oral terbinafine for 2 mo,but the patient still had painful papules,nodules and abscesses on her face.Then,we adjusted the treatment to itraconazole 400 mg/d for 8 wk based on the in vitro antifungal susceptibility testing results.The skin lesions improved significantly,and there was no recurrence during follow-up.CONCLUSION This case revealed that facial injection of hyaluronic acid may cause serious MG.Antifungal susceptibility testing should be considered in the treatment of MG caused by Trichophyton rubrum.展开更多
Background:Little is known about stage 1 and 2 pressure injuries that are health care-acquired.We report incidence rates of health care-acquired stage 1 and stage 2 pressure injuries,and,estimate the excess length of ...Background:Little is known about stage 1 and 2 pressure injuries that are health care-acquired.We report incidence rates of health care-acquired stage 1 and stage 2 pressure injuries,and,estimate the excess length of stay using four competing analytic methods.We discuss the merits of the different approaches.Methods:We calculated monthly incidence rates for stage 1 and 2 health care-acquired pressure injuries occurring in a large Singapore acute care hospital.To estimate excess stay,we conducted unadjusted comparisons with a control cohort,performed linear regression and then generalized linear regression with a gamma distribution.Finally,we fitted a simple state-based model.The design for the cost attribution work was a retrospective matched cohort study.Results:Incidence rates in 2016 were 0.553%(95%confidence interval[CI]0.55,0.557)and 0.469%(95%CI 0.466,0.472)in 2017.For data censored at 60 days’maximum stay,the unadjusted comparisons showed the highest excess stay at 17.68(16.43-18.93)days and multi-state models showed the lowest at 1.22(0.19,2.23)days.Conclusions:Poor-quality methods for attribution of excess length of stay to pressure injury generate inflated estimates that could mislead decision makers.The findings from the multi-state model,which is an appropriate method,are plausible and illustrate the likely bed-days saved from lowering the risk of these events.Stage 1 and 2 pressure injuries are common and increase costs by prolonging the length of stay.There will be economic value investing in prevention.Using biased estimates of excess length of stay will overstate the potential value of prevention.展开更多
Objective:To estimate the costs from delaying major amputation in patients with concurrent diabetic foot ulcer and peripheral vascular disease.We seek to model economic benefits from saved costs from promoting timely ...Objective:To estimate the costs from delaying major amputation in patients with concurrent diabetic foot ulcer and peripheral vascular disease.We seek to model economic benefits from saved costs from promoting timely major amputations among these patients.Methods:Retrospective modeling using data from National University Hospital,Singapore.We identified patients who might have delayed major amputations by applying a hierarchical clustering algorithm.We then modeled the transitions of all patients over time with a Markov process using a number of relevant health states to enable estimation of cost outcomes.We next summarized the expected changes to the bed days used and cost outcomes arising from reassigning some patients who may have had a delayed amputation to timely amputation.The findings from the sample were scaled to reflect national incidence rates for this disease for the years 2014-2019 in Singapore.Results and Conclusions:Nine of the 137 patients(6.57%)would be suitable for a major amputation at 3 months,yet in reality,their amputation was delayed.Based on this,and assuming a timely amputation is done for the entire population of patients in Singapore we expect annual savings of 264,791 bed days and $211 million in costs.These findings are preliminary and uncertain.The value of this paper is to show a method for estimating outcomes,report the findings from a small sample,and stimulate future research.New cohort studies might be designed to capture a wider range of outcomes and recruit a larger sample of individuals.展开更多
Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to ...Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.展开更多
Microneedles(MNs)is an emerging technology that employs needles ranging from 10 to 1000μm in height,as a minimally invasive technique for various procedures such as therapeutics,disease monitoring and diagnostics.The...Microneedles(MNs)is an emerging technology that employs needles ranging from 10 to 1000μm in height,as a minimally invasive technique for various procedures such as therapeutics,disease monitoring and diagnostics.The commonly used method of fabrication,micromolding,has the advantage of scalability,however,micromolding is unable to achieve rapid customizability in dimensions,geometries and architectures,which are the pivotal factors determining the functionality and efficacy of the MNs.3D printing offers a promising alternative by enabling MN fabrication with high dimensional accuracy required for precise applications,leading to improved performance.Furthermore,enabled by its customizability and one-step process,there is propitious potential for growth for 3D-printed MNs especially in the field of personalized and on-demand medical devices.This review provides an overview of considerations for the key parameters in designing MNs,an introduction on the various 3D-printing techniques for fabricating this new generation of MNs,as well as highlighting the advancements in biomedical applications facilitated by 3D-printed MNs.Lastly,we offer some insights into the future prospects of 3D-printed MNs,specifically its progress towards translation and entry into market.展开更多
N6-methyladenosine(m^(6)A)is the most abundant internal modification on RNA.It is a dynamical and reversible process,which is regulated by m^(6)A methyltransferase and m^(6)A demethylase.The m^(6)A modified RNA can be...N6-methyladenosine(m^(6)A)is the most abundant internal modification on RNA.It is a dynamical and reversible process,which is regulated by m^(6)A methyltransferase and m^(6)A demethylase.The m^(6)A modified RNA can be specifically recognized by the m^(6)A reader,leading to RNA splicing,maturation,degradation or translation.The abnormality of m^(6)A RNA modification is closely related to a variety of biological processes,especially the occurrence and development of tumors.Recent studies have shown that m^(6)A RNA modification is involved in the pathogenesis of skin cancers.However,the precise molecular mechanisms of m^(6)A-mediated cutaneous tumorigenesis have not been fully elucidated.Therefore,this review will summarize the biological characteristics of m^(6)A modification,its regulatory role and mechanism in skin cancers,and the recent research progress of m^(6)A-related molecular drugs,aiming to provide new ideas for clinical diagnosis and targeted therapy of cutaneous cancers.展开更多
文摘Biofabrication and biomanufacturing are rapidly transforming how materials,therapeutics,and functional biological constructs are produced.These fields integrate developments in sustainable biomaterials,precision fabrication,biological systems,and data-driven engineering to produce scalable,efficient,and environmentally aligned production pathways.This review highlights recent scientific advances led by researchers in Singapore,focusing on three interconnected pillars:sustainable bio derived materials,enabling fabrication and manufacturing technologies,and emerging applications.We first examine the expanding use of biomass-derived feedstocks,including human hair keratin,aquaculture side-streams,and plant-derived polysaccharides,which support circular and resource-conscious material development.We then present advances in biofabrication technologies,including electrospinning,three-dimensional bioprinting,and metal additive manufacturing,that enable improved control over the structure,function,and manufacturability of biomedical and functional constructs.Emerging applications,such as machine learning-assisted additive manufacturing,food biomanufacturing,regenerative cell therapy,microneedles,and bioelectronics,exemplify how biofabrication and biomanufacturing are increasingly interrelated across the health,materials,and technological domains.These research contributions from Singapore exemplify how sustainable feedstocks,digital and automated fabrication platforms,and biologically driven applications are shaping the evolving landscape of biofabrication and biomanufacturing.The convergence of materials science,biological engineering,and advanced manufacturing continues to enable new opportunities for innovation in biomedical,industrial,and societal contexts.
文摘Many studies on aging have focused on evaluating differences between older and younger people, but only a few have focused on differences in skin properties among subjects from the same age group according to their skin aging status. In this study, we evaluated the facial skin condition and life style factors in 110 Korean women aged 25 to 35 in an attempt to evaluate factors which may affect the skin aging status in the initial aging phase. The facial skin condition of 110 healthy Korean women was assessed over two successive 6-month periods, summer and winter. Using clinical assessments including aging, wrinkles and skin’s elasticity values, the subjects were divided into 7 groups. Then, various facial skin conditions and life style factors were examined between a severe aging group and mild aging group. In the severe aging group, the mean value pH was lower and the mean value of water content was slightly lower than that of women in the mild aging group. Also, the seasonal site variation in water content and sebum secretion level were significantly higher in the severe aging group than in the mild aging group. Topical sunscreen using percentage was not significantly different between the two groups. However, the number of cosmetic subject use was slightly higher in the mild aging group than in the severe aging group. The study suggested that there were several differences in skin characteristics between women in the severe aging group and in the mild aging group at the initial aging phase. Seasonal site variation between cheek and forehead was the most dominant differences. We also considered that life style factors such as cosmetic use could affect skin aging status.
文摘OBJECTIVES: Skin characteristics change depending on the external environment such as UV, temperature and humidity. But the research how to affect the regional climate, age and seasonal variation on the skin conditions was not well studied. Therefore, we investigated the seasonal variation in the skin by comparing Beijing women and Guangzhou women by age groups. METHODS: 440 healthy Chinese women participated in this study. The skin hydration, sebum secretion, TEWL and skin pH were measured on the cheek front. All the parameters were analyzed in terms of the age, season and region. RESULTS: The skin hydration in Beijing was lower than that in Guangzhou and significantly decreased during winter than summer. The sebum secretion in their 20s and 30s was significantly high in summer in both regions, and this phenomenon was more remarkable in Guangzhou (p CONCLUSIONS: Skin hydration and barrier function decreased more during a cold, dry winter than summer. The barrier dysfunctions such as an increase in TEWL and pH occurred more commonly in old age groups. The greater the differences between summer and winter climates, the greater damage to skin barrier and skin hydration. The sebum secretion was more affected by hot, humid summers. Further, the aged skin was influenced by seasonal variation except for sebum secretion.
文摘Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy, which causes substantial morbidities and mortalities. Although the significant increase in the understanding of skin cancer formation and the development of novel personalized drug regimens have occurred, new treatment options are always of need. The use of natural compounds to alleviate the symptoms or even to prevent and treat cancer has long been proposed. Specifically, the use of marine-based organisms as a source for cancer cure and remedy is being evaluated extensively. The objective of the current study was to assess the ability of the green microalgae Dunaliella salina, the Dead-Sea-derived Haloferax volcanii, and its combinations to treat skin cancer in vitro. The results demonstrate the Dunaliella and Haloferax can reduce sarcoma and basal cell carcinoma cellular growth. Importantly, their combination acts synergistically in a caspase-3 independent manner. Moreover, a synergistic action was found when evaluated sarcoma cell invasion rate, which was completely blocked at pharmacological relevant amounts of the compounds. Collectively, the results demonstrate that the combination of Haloferax volcanii and Dunaliella salina can be used as a new treatment for skin cancer. The specific mechanism of action and further in vivo validation studies are of need.
基金supported by the National Natural Science Foundation of China(No.U21A20379)National Key Research and Development Program of China(No.2021YFA1101000,2021YFA1101004)+1 种基金Research Fund for Foreign Scholars of China(No.82250710176)Leading Innovation and Entrepreneurship Team of Hangzhou(No.TD2020006).
文摘Skin, as the body's largest organ, acts as the primary defense mechanism against infection and injury. The maintenance ofskin health heavily relies on the regulation of epidermal stem cells, crucial for ensuring epidermal homeostasis, hair regeneration, andthe repair of epidermal injuries. Recent studies have placed a growing emphasis on G protein-coupled receptor (GPCR) in the contextof understanding epidermal stem cells, uncovering its significant role in determining their fate. The activation of GPCR triggers thesubsequent dissociation of the βγ subunits from the α subunit of G protein, leading to the modulation of various downstreamsignaling pathways, such as the WNT-BMP signaling crosstalk and the Gαs-PKA signaling pathway. These pathways collectivelyinfluence the fate of epidermal stem cells. Consequently, targeted GPCR therapy has emerged as a promising strategy for improvingskin health by orchestrating the fate of epidermal stem cells, unveiling potential therapeutic targets that demand further investigation.
文摘<strong>Background:</strong> Retinol (RE) is deeply involved in skin processes, therefore it is widely formulated in cosmetics, primarily as an anti-aging ingredient. Despite <span>its efficacy, the safety profile of RE is controversial. <b>Objectives:</b> Pretinol (PRE) complex was formulated with two RE precursors, <i>β</i>-Carotene and Niacinamide,</span><span> </span>in order to deliver retinol-like skin benefits with healthier characteristics, as<span>suming that skin enzymes will enable safe RE supply on spot. <b>Methods:</b> The expres</span><span>sion levels of hyaluronic acid, Tumor Necrosis Factor alpha (TNF<i>α</i>) and In</span><span>terleukin 1 alpha (IL-1<i>α</i>), were measured using various skin models before and</span><span> </span><span>after exposure to PRE and RE. Full genome microarray was performed and the</span> <span>affected genes and pathways were analyzed. <b>Results:</b> Following fibroblasts exposure to PRE, the natural synthesis of hyaluronic acid is significantly elevated</span><span>.</span><span> </span><span>Skin safety, demonstrated via cytokines expression on <i>ex-vivo</i> skin, results with TNF<i>α</i> and IL-1<i>α</i> elevation by RE application. In contrary PRE significantly reduces</span> TNF<i>α</i> while IL-1<i>α</i> is not affected. These results establish skin safety advantage of PRE <i>vs</i> RE. Microarray results examined on skin equivalents reveal <span>the involvement of PRE in inflammatory attenuation. <b>Conclusions:</b> Formulat</span>ing RE precursors as a safe source for RE is partially supported. PRE presents a skin benefit in parallel to RE, while PRE characteristics are suggested to be safer to skin.
文摘Objectives: Exposing skin to moderate ionic osmotic stress (MIOS) triggers several biochemical responses. The objective of this work is to reveal the mechanism triggered by MIOS on the skin surface. Furthermore, this work aims to study the involvement of the Nrf2 (nuclear factor erythroid-2-related factor 2) pathway, activated by MIOS, and its beneficial effect in protecting skin against stress via the stimulation of phase II enzymes. Methods: HaCaT cells and human skin organ culture were exposed to Dead Sea Water (DSW) as MIOS inducers and the induction of internal ROS elevation, Nrf2 translocation, mRNA gene expressions of the phase II enzymes, heme-oxygenase 1 (HO1), and Catalase (CAT) were determined. Results: Skin exposure to MIOS increases Nrf2 translocation to the nucleus, leading to increased levels of ROS, HO1, and CAT. Furthermore, exposing skin to MIOS promotes protection against UVB-related risks. This is demonstrated by attenuation of the expression of biomarkers, related to UVB-induced damage, Caspase-3, IL-8, and IL-1β. Conclusions: Skin exposure to MIOS leads to the activation of Nrf2 skin defense pathway and, therefore, could present beneficial advantages to human skin health, as demonstrated on human skin models. The beneficial effects of MIOS, induced by DSW are significantly superior to eq. NaCl brine, suggests that MIOS protection of skin against stress is partially related to specific mineral combinations.
基金the Scientific Research Project of Peking University Shenzhen Hospital,No. JCYJ2018011the"San-ming"Project of Medicine in Shenzhen,No. SZSM201812059。
文摘BACKGROUND Facial cosmetic procedures become popular for people with a desire to have a younger appearance,and cosmetic technology has developed rapidly over the past several decades.However,increasing complications related to cosmetic injections have been reported,and infection is one of the most serious problems and can cause anxiety and facial injury.We here report a case of Majocchi’s granuloma(MG)caused by Trichophyton rubrum after facial injection of hyaluronic acid.CASE SUMMARY A 37-year-old woman presented to our hospital with a history of red papules,nodules,and abscesses on her left zygomatic arch for 2 mo.She had received a cosmetic injection of hyaluronic acid on the left side of her face prior to the appearance of the lesions.MG caused by Trichophyton rubrum after facial injection of hyaluronic acid was diagnosed based on morphology and molecular biological identification.In vitro antifungal susceptibility testing was conducted according to the Clinical and Laboratory Standards Institute M38-A2 method.Minimal inhibitory concentrations were used to evaluate the antifungal susceptibility.The antifungal agents and their minimal inhibitory concentrations for the strain were terbinafine(<0.5μg/mL),itraconazole(0.06μg/mL),amphotericin B(0.25μg/mL),fluconazole(32μg/mL),voriconazole(0.125μg/mL),posaconazole(0.125μg/mL),and isavuconazole(0.06μg/mL).We initially administered 250 mg/d oral terbinafine for 2 mo,but the patient still had painful papules,nodules and abscesses on her face.Then,we adjusted the treatment to itraconazole 400 mg/d for 8 wk based on the in vitro antifungal susceptibility testing results.The skin lesions improved significantly,and there was no recurrence during follow-up.CONCLUSION This case revealed that facial injection of hyaluronic acid may cause serious MG.Antifungal susceptibility testing should be considered in the treatment of MG caused by Trichophyton rubrum.
基金Pre-Positioning Programme,Grant/Award Number:H1X/01/a0/OX9Agency for Science,Technology and Research(A*STAR)。
文摘Background:Little is known about stage 1 and 2 pressure injuries that are health care-acquired.We report incidence rates of health care-acquired stage 1 and stage 2 pressure injuries,and,estimate the excess length of stay using four competing analytic methods.We discuss the merits of the different approaches.Methods:We calculated monthly incidence rates for stage 1 and 2 health care-acquired pressure injuries occurring in a large Singapore acute care hospital.To estimate excess stay,we conducted unadjusted comparisons with a control cohort,performed linear regression and then generalized linear regression with a gamma distribution.Finally,we fitted a simple state-based model.The design for the cost attribution work was a retrospective matched cohort study.Results:Incidence rates in 2016 were 0.553%(95%confidence interval[CI]0.55,0.557)and 0.469%(95%CI 0.466,0.472)in 2017.For data censored at 60 days’maximum stay,the unadjusted comparisons showed the highest excess stay at 17.68(16.43-18.93)days and multi-state models showed the lowest at 1.22(0.19,2.23)days.Conclusions:Poor-quality methods for attribution of excess length of stay to pressure injury generate inflated estimates that could mislead decision makers.The findings from the multi-state model,which is an appropriate method,are plausible and illustrate the likely bed-days saved from lowering the risk of these events.Stage 1 and 2 pressure injuries are common and increase costs by prolonging the length of stay.There will be economic value investing in prevention.Using biased estimates of excess length of stay will overstate the potential value of prevention.
基金Agency for Science,Technology and Research(A*STAR),Grant/Award Number:H1901a00Y9/and H17/01/a0/0CC9。
文摘Objective:To estimate the costs from delaying major amputation in patients with concurrent diabetic foot ulcer and peripheral vascular disease.We seek to model economic benefits from saved costs from promoting timely major amputations among these patients.Methods:Retrospective modeling using data from National University Hospital,Singapore.We identified patients who might have delayed major amputations by applying a hierarchical clustering algorithm.We then modeled the transitions of all patients over time with a Markov process using a number of relevant health states to enable estimation of cost outcomes.We next summarized the expected changes to the bed days used and cost outcomes arising from reassigning some patients who may have had a delayed amputation to timely amputation.The findings from the sample were scaled to reflect national incidence rates for this disease for the years 2014-2019 in Singapore.Results and Conclusions:Nine of the 137 patients(6.57%)would be suitable for a major amputation at 3 months,yet in reality,their amputation was delayed.Based on this,and assuming a timely amputation is done for the entire population of patients in Singapore we expect annual savings of 264,791 bed days and $211 million in costs.These findings are preliminary and uncertain.The value of this paper is to show a method for estimating outcomes,report the findings from a small sample,and stimulate future research.New cohort studies might be designed to capture a wider range of outcomes and recruit a larger sample of individuals.
基金support from Singapore Agency for Science,Technology and Research(A*STAR)Science and Engineering Research Council Additive Manufacturing for Biological Materials(AMBM)program(A18A8b0059,Singapore)City University of Hong Kong(#9610472,China)+1 种基金General Research Fund(GRF)from University Grant Committee of Hong Kong(UGC)Research Grant Council(RGC)(#9042951,China)NSFC/RGC Joint Research Scheme(N_City U118/20,China)
文摘Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.
基金supported by the National Additive Manufacturing Innovative Cluster(NAMIC)POC Funding,Agency for Science,Technology and Research(A*STAR)Career Development Fund and BMRC Central Research Fund(CRF,ATR)NHG Medical Technologies&Innovations(CMTi)and National Health Innovation Centre Singapore(NHIC)Joint MedTech Grant.
文摘Microneedles(MNs)is an emerging technology that employs needles ranging from 10 to 1000μm in height,as a minimally invasive technique for various procedures such as therapeutics,disease monitoring and diagnostics.The commonly used method of fabrication,micromolding,has the advantage of scalability,however,micromolding is unable to achieve rapid customizability in dimensions,geometries and architectures,which are the pivotal factors determining the functionality and efficacy of the MNs.3D printing offers a promising alternative by enabling MN fabrication with high dimensional accuracy required for precise applications,leading to improved performance.Furthermore,enabled by its customizability and one-step process,there is propitious potential for growth for 3D-printed MNs especially in the field of personalized and on-demand medical devices.This review provides an overview of considerations for the key parameters in designing MNs,an introduction on the various 3D-printing techniques for fabricating this new generation of MNs,as well as highlighting the advancements in biomedical applications facilitated by 3D-printed MNs.Lastly,we offer some insights into the future prospects of 3D-printed MNs,specifically its progress towards translation and entry into market.
基金supported by grants from the National Natural Science Foundation of China(No.82103726,82103727,and 81803138)Shenzhen Science and Technology Program,China(No.JCYJ20210324110008023)+2 种基金Shenzhen Sanming Project,China(No.SZSM201812059)Shenzhen Key Medical Discipline Construction Fund,China(No.SZXK040)Scientific Research Foundation of Peking University Shenzhen Hospital,China(No.KYQD2021016,KYQD2021038,KYQD2021039,KYQD2021049,and KYQD2021052).
文摘N6-methyladenosine(m^(6)A)is the most abundant internal modification on RNA.It is a dynamical and reversible process,which is regulated by m^(6)A methyltransferase and m^(6)A demethylase.The m^(6)A modified RNA can be specifically recognized by the m^(6)A reader,leading to RNA splicing,maturation,degradation or translation.The abnormality of m^(6)A RNA modification is closely related to a variety of biological processes,especially the occurrence and development of tumors.Recent studies have shown that m^(6)A RNA modification is involved in the pathogenesis of skin cancers.However,the precise molecular mechanisms of m^(6)A-mediated cutaneous tumorigenesis have not been fully elucidated.Therefore,this review will summarize the biological characteristics of m^(6)A modification,its regulatory role and mechanism in skin cancers,and the recent research progress of m^(6)A-related molecular drugs,aiming to provide new ideas for clinical diagnosis and targeted therapy of cutaneous cancers.
