Current clinical evidence is insufficient to support HMME-PDT as the first choice of treatment for young children with port wine birthmarks.

BACKGROUND: Port wine birthmark (PWB) is a congenital vascular malformation of the skin. Pulsed dye laser (PDL) is the "gold standard" for the treatment of PWB globally. Hematoporphyrin monomethyl ether (HMME or hemoporfin)-mediated photodynamic therapy (HMME-PDT) has emerged as the first choice for PWB treatment, particularly for young children, in many major hospitals in China during the past several decades. AIM: To evaluate whether HMME-PDT is superior to PDL by comparing the clinical efficacies of both modalities. METHOD: PubMed records were searched for all relevant studies of PWB treatment using PDL (1988-2023) or HMME-PDT (2007-2023). Patient characteristics and clinical efficacies were extracted. Studies with a quartile percentage clearance or similar scale were included. A mean color clearance index (CI) per study was calculated and compared among groups. An overall CI (C0), with data weighted by cohort size, was used to evaluate the final efficacy for each modality. RESULT: A total of 18 HMME-PDT studies with 3910 patients in China were eligible for inclusion in this analysis. Similarly, 40 PDL studies with 5094 patients from nine different countries were eligible for inclusion in this analysis. Over 58% of patients in the HMME-PDT studies were minors (<18 years old). A significant portion (21.3%) were young children (<3 years old). Similarly, 33.2% of patients in the PDL studies were minors. A small proportion (9.3%) was young children. The overall clearance rates for PDL were slightly, but not significantly, higher than those for HMME-PDT in cohorts with patients of all ages (C0, 0.54 vs. 0.48, p = 0.733), subpopulations with only minors (C0, 0.54 vs. 0.46, p = 0.714), and young children (C0, 0.67 vs. 0.50, p = 0.081). Regrettably, there was a lack of long-term data on follow-up evaluations for efficacy and impact of HMME-PDT on young children in general, and central nervous system development in particular, because their blood-brain barriers have a greater permeability as compared to adults. CONCLUSION: PDL shows overall albeit insignificantly higher clearance rates than HMME-PDT in patients of all ages; particularly statistical significance is nearly achieved in young children. Collectively, current evidence is insufficient to support HMME-PDT as the first choice of treatment of PWBs in young children given: (1) overall inferior efficacy as compared to PDL; (2) risk of off-target exposure to meningeal vasculature during the procedure; (3) administration of steriods for mitigation of side effects; -and (4) lack of long-term data on the potential impact of HMME on central nervous system development in young children.

Pharmacological Activities, Therapeutic Effects, and Mechanistic Actions of Trigonelline.

Trigonelline (TRG) is a natural polar hydrophilic alkaloid that is found in many plants such as green coffee beans and fenugreek seeds. TRG potentially acts on multiple molecular targets, including nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor γ, glycogen synthase kinase, tyrosinase, nerve growth factor, estrogen receptor, amyloid-ß peptide, and several neurotransmitter receptors. In this review, we systematically summarize the pharmacological activities, medicinal properties, and mechanistic actions of TRG as a potential therapeutic agent. Mechanistically, TRG can facilitate the maintenance and restoration of the metabolic homeostasis of glucose and lipids. It can counteract inflammatory constituents at multiple levels by hampering pro-inflammatory factor release, alleviating inflammatory propagation, and attenuating tissue injury. It concurrently modulates oxidative stress by the blockage of the detrimental Nrf2 pathway when autophagy is impaired. Therefore, it exerts diverse therapeutic effects on a variety of pathological conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional effects, including neuroprotection from neurodegenerative disorders and diabetic peripheral neuropathy, neuromodulation, mitigation of cardiovascular disorders, skin diseases, diabetic mellitus, liver and kidney injuries, and anti-pathogen and anti-tumor activities. Further validations are required to define its specific targeting molecules, dissect the underlying mechanistic networks, and corroborate its efficacy in clinical trials.

Protective roles of tRNA-derived small RNA tRF-Ile-AAT-019 in pathological progression of psoriasis.

Psoriasis is a chronic recurrent inflammatory skin disease that is characterized by abnormal proliferation and differentiation of keratinocytes (KCs), angiogenesis and skin inflammation. Transfer RNA fragments (tRFs) are tRNA-derived small RNAs (tsRNAs), which possess regulatory functions in many diseases. Their potential roles in the pathological development of psoriasis have not been established. We first identified differentially expressed (DE) tRFs from psoriatic skin lesions using small RNA sequencing, and collected additional clinical samples for validation. Then, we investigated the function and mechanism of target tRFs in vitro. As a result of our investigation: we identified 234 DE transcripts in psoriatic skin lesions compared with normal controls. Further functional analysis showed the downregulation of tRF-Ile-AAT-019 in psoriatic lesions plays a critical role in pathogenesis since it could target 3'UTR of the serine protease serpin protein E1 (SERPINE1) gene. We next demonstrated that tRF-Ile-AAT-019 could suppress SERPINE1, thus leading to decreased expressions of vascular endothelial growth factor but increased expressions of keratinocytes (KCs) differentiation markers including Keratin1 and Involucrin. In conclusion, tRF-Ile-AAT-019 plays a protective role in the pathological progression of psoriasis via targeting SERPINE1, resulting in regulation of KCs differentiation and vascular proliferation biomarkers and providing a potential novel targeting pathway for the disease treatment.

Spike protein of SARS-CoV-2 activates macrophages and contributes to induction of acute lung inflammation in male mice.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a crucial role in mediating viral entry into host cells. However, whether it contributes to pulmonary hyperinflammation in patients with coronavirus disease 2019 is not well known. In this study, we developed a spike protein-pseudotyped (Spp) lentivirus with the proper tropism of the SARS-CoV-2 spike protein on the surface and determined the distribution of the Spp lentivirus in wild-type C57BL/6J male mice that received an intravenous injection of the virus. Lentiviruses with vesicular stomatitis virus glycoprotein (VSV-G) or with a deletion of the receptor-binding domain (RBD) in the spike protein [Spp (∆RBD)] were used as controls. Two hours postinfection (hpi), there were 27-75 times more viral burden from Spp lentivirus in the lungs than in other organs; there were also about 3-5 times more viral burden from Spp lentivirus than from VSV-G lentivirus in the lungs, liver, kidney, and spleen. Deletion of RBD diminished viral loads in the lungs but not in the heart. Acute pneumonia was observed in animals 24 hpi. Spp lentivirus was mainly found in SPC+ and LDLR+ pneumocytes and macrophages in the lungs. IL6, IL10, CD80, and PPAR-γ were quickly upregulated in response to infection in the lungs as well as in macrophage-like RAW264.7 cells. Furthermore, forced expression of the spike protein in RAW264.7 cells significantly increased the mRNA levels of the same panel of inflammatory factors. Our results demonstrated that the spike protein of SARS-CoV-2 confers the main point of viral entry into the lungs and can induce cellular pathology. Our data also indicate that an alternative ACE2-independent viral entry pathway may be recruited in the heart and aorta.

Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients.

BACKGROUND: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. OBJECTIVE: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. METHODS: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. RESULTS: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients. CONCLUSIONS: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.

Efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis by rebalancing skin microecology.

This study investigated the mechanism and efficacy of topical acidified aliphatic ester for treatment of axillary osmidrosis (AO). A total of 32 AO patients were enrolled in this study. In the initial pilot study, 20 patients were double-blindly, randomly divided into acidified aliphatic ester or aliphatic ester treatment groups, followed by efficacy evaluation after 4 weeks. Then, all patients (n = 32) were treated with topical acidified aliphatic ester for 16 weeks. Efficacy was evaluated at every 4 weeks, and at 3- and 6-month follow-ups. Changes of pH values and microecology at targeting sites were analyzed. In the first cohort (n = 20) of pilot study, acidified aliphatic ester showed significantly higher curative rate (60% vs 10%, P < .05) and effective rate (90% vs 30%; P < .05) than aliphatic ester. For the next 16 weeks, 25 of 32 cases completed treatment. Curative rate showed gradual and significant increases from 64% to 96% during the treatment courses (P = .001); it slightly but insignificantly decreased at 3- and 6- month follow-ups. Abundance of Corynebacterium and Anaerobic bacteria decreased while Staphylococcus increased after treatments. Axillary pH values negatively correlated with Staphylococcus abundance (r = -.40, P = .01) and positively with Corynebacterium abundance (r = .64, P = .01). We concluded that topical acidified aliphatic ester could effectively alleviate conditions of AO patients by reducing value of axillary pH and rebalancing axillary microecology.

Efficacy of Erbium-Doped Yttrium Aluminium Garnet 2,940 and 1,064 nm Laser Treatment for Facial Rejuvenation-A Randomized Controlled Split-Face Clinical Trial.

BACKGROUND: The 2,940 nm erbium-doped yttrium aluminium garnet and 1,064 nm neodymium-doped yttrium aluminium garnet lasers have been widely applied in facial rejuvenation, but no randomized trials exist to evaluate the efficacy of the combination treatment. OBJECTIVE: The efficacy of the combined treatment for facial rejuvenation. MATERIALS AND METHODS: A total of 20 subjects with facial aging were enrolled and randomly assigned into 2 groups: one side of the face was treated with a 2,940 nm or 1,064 nm laser alone and the other side was treated with the combined lasers. The patients were treated by 3 sessions with 1-month intervals. The efficacies were quantitatively accessed by digitalized high-resolution photographs. RESULTS: The 1,064 nm laser alone showed significant improvements on indexes of skin texture, spore, brown spots, elasticity, and melanin as compared with the baseline (p < .05). The 2,940 nm laser alone showed significant improvements on indexes of wrinkle, texture, pore, and elasticity (p < .05). The combined treatments showed significant improvements on the abovementioned indexes as compared with either a 1,064 nm or 2,940 nm laser treatment (p < .05). CONCLUSION: A combination of 1,064 nm and 2,940 nm laser treatment renders significantly better efficacies for facial rejuvenation as compared with a 2,940 nm or 1,064 nm laser alone.

Fecal occult blood and urinary cytology tests for rapid screening of inflammatory infection in the gastrointestinal and urological systems in patients with Coronavirus disease 2019.

BACKGROUND: Gastrointestinal infections (GI) and urological infections (UI) have not been fully addressed in COVID-19 patients. We aimed to evaluate the values of routine fecal occult blood (FOB) test and urinary cytology test (UCT) for screening of GI and UI in COVID-19 patients. METHODS: In this retrospective study, COVID-19 patients without associated comorbidities were divided into FOB- or UCT-positive or FOB- or UCT-negative groups. Their clinical characteristics and laboratory findings were then compared. RESULTS: A total of 13.6% of patients (47 of 345) tested positive for FOB, and 57.4% (27 of 47) of these patients lacked gastrointestinal symptoms. A total of 30.1% of patients (104 of 345) exhibited gastrointestinal symptoms, and 38.0% (131 of 345) were positive for either FOB or gastrointestinal symptoms. FOB-positive patients possessed significantly higher levels of C-reactive protein and fewer lymphocytes than FOB-negative patients. A total of 36.9% of patients (80 of 217) exhibited positive UCT, and 97.5% (78 of 80) of these patients possessed normal levels of serum markers for renal injuries. Significant differences in age and sex ratios were observed between the UCT-positive and UCT-negative groups, and 72.4% (42 of 58) of female patients over 60 years old were UCT-positive. CONCLUSIONS: Fecal occult blood test in combination with gastrointestinal symptoms could serve as a simple and useful screening approach for GI diagnoses for COVID-19. Age and sex are risk factors for UI in COVID-19 patients. UCT could be a sensitive tool for assessing early UI at a stage in which serum markers for renal injuries appear normal.

Cholesterol: A new game player accelerating vasculopathy caused by SARS-CoV-2?

The pandemic of coronavirus disease (COVID-19) has become a global threat to public health. Functional impairments in multiple organs have been reported in COVID-19, including lungs, heart, kidney, liver, brain, and vascular system. Patients with metabolic-associated preconditions, such as hypertension, obesity, and diabetes, are susceptible to experiencing severe symptoms. The recent emerging evidence of coagulation disorders in COVID-19 suggests that vasculopathy appears to be an independent risk factor promoting disease severity and mortality of affected patients. We recently found that the decreased levels of low-density lipoprotein cholesterols (LDL-c) correlate with disease severity in COVID-19 patients, indicating pathological interactions between dyslipidemia and vasculopothy in patients with COVID-19. However, this clinical manifestation has been unintentionally underestimated by physicians and scientific communities. As metabolic-associated morbidities are generally accompanied with endothelial cell (EC) dysfunctions, these pre-existing conditions may make ECs more vulnerable to SARS-CoV-2 attack. In this mini-review, we summarize the metabolic and vascular manifestations of COVID-19 with an emphasis on the association between changes in LDL-c levels and the development of severe symptoms as well as the pathophysiologic mechanisms underlying the synergistic effect of LDL-c and SARS-CoV-2 on EC injuries and vasculopathy.

Elevations of serum cancer biomarkers correlate with severity of COVID-19.

In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 µg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 µg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 µg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 µg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.

Characterization of Laser-Resistant Port Wine Stain Blood Vessels Using In Vivo Reflectance Confocal Microscopy.

BACKGROUND AND OBJECTIVES: Port wine stain (PWS) is a congenital vascular malformation of the human skin. Laser is the treatment of choice for PWS. Laser-resistant PWS is one crucial factor accounting for inadequate treatment outcome, which needs to be fully characterized. This study aims to quantitatively characterize the morphology of laser-resistant PWS blood vessels in the upper papillary dermis using in vivo reflectance confocal microscopy (RCM). STUDY DESIGN/MATERIALS AND METHODS: A total of 42 PWS subjects receiving laser treatment from August 2016 through July 2018 were enrolled into this study. Thirty-three subjects had facial PWS; nine had extremity PWS. All subject's PWS received multiplex 585/1,064 nm laser treatment. RCM images were taken before and after treatment. The density, diameter, blood flow, and depth of PWS blood vessels were analyzed. RESULTS: We found 44.4% PWS on the extremities (four out of nine subjects) were laser-resistant, which was significantly higher (P < 0.001) when compared with those PWS on the face (15.2%, 5 out of 33 subjects). The laser-resistant facial PWS blood vessels had significantly higher blood flow (1.35 ± 0.26 U vs. 0.89 ± 0.22 U, P < 0.001), larger blood vessel diameters (109.60 ± 18.24 µm vs. 84.36 ± 24.04 µm, P = 0.033) and were located deeper in the skin (106.01 ± 13.87 µm vs. 87.82 ± 12.57 µm, P < 0.001) in the skin when compared with laser-responsive PWS on the face. The average PWS blood vessel density (17.01 ± 4.63/mm2 vs. 16.61 ± 4.44/mm2 , P = 0.857) was not correlated to the laser resistance. CONCLUSIONS: Laser-resistant PWS blood vessels had significantly higher blood flow, larger diameters, and were located deeper in the skin. RCM can be a valuable tool for a prognostic evaluation on laser-resistant lesions before treatment, thereby providing guidance for tailored laser treatment protocols, which may improve the therapeutic outcome. The limitations for this study include relative small sample size and acquisitions of different blood vessels before and after 2 months of treatment. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

The Pathogenesis of Port Wine Stain and Sturge Weber Syndrome: Complex Interactions between Genetic Alterations and Aberrant MAPK and PI3K Activation.

Port wine stain (PWS) is a congenital vascular malformation involving human skin. Approximately 15-20% of children a facial PWS involving the ophthalmic (V1) trigeminal dermatome are at risk for Sturge Weber syndrome (SWS), a neurocutaneous disorder with vascular malformations in the cerebral cortex on the same side of the facial PWS lesions. Recently, evidence has surfaced that advanced our understanding of the pathogenesis of PWS/SWS, including discoveries of somatic genetic mutations (GNAQ, PI3K), MAPK and PI3K aberrant activations, and molecular phenotypes of PWS endothelial cells. In this review, we summarize current knowledge on the etiology and pathology of PWS/SWS based on evidence that the activation of MAPK and/or PI3K contributes to the malformations, as well as potential futuristic treatment approaches targeting these aberrantly dysregulated signaling pathways. Current data support that: (1) PWS is a multifactorial malformation involving the entire physiological structure of human skin; (2) PWS should be pathoanatomically re-defined as "a malformation resulting from differentiation-impaired endothelial cells with a progressive dilatation of immature venule-like vasculatures"; (3) dysregulation of vascular MAPK and/or PI3K signaling during human embryonic development plays a part in the pathogenesis and progression of PWS/SWS; and (4) sporadic low frequency somatic mutations, such as GNAQ, PI3K, work as team players but not as a lone wolf, contributing to the development of vascular phenotypes. We also address many crucial questions yet to be answered in the future research investigations.

Activation of RhoA, Smad2, c-Src, PKC-ßII/δ and JNK in atopic dermatitis.

Atopic dermatitis is a multifactorial skin disease characterised by chronic and relapsing inflammation whose pathogenesis is incompletely understood. We found that the expression of TGFßR1 and the activation of SMAD2, RhoA, JNK, PKC-ßII/δ and c-Src were upregulated in the infiltrated inflammatory cells, fibroblasts and vasculatures in the dermis and epidermis. In addition, increases in the expression of TGFßR1 and phosphorylation levels of JNK and c-Src were positively correlated with the inflammatory progression of atopic dermatitis severity.

Activation of PKCα and PI3K Kinases in Hypertrophic and Nodular Port Wine Stain Lesions.

Port wine stain (PWS) is a congenital, progressive vascular malformation. Many patients with PWS develop hypertrophy and discrete nodularity during their adult life, but the mechanism(s) remain incompletely understood. In this study, we attempted to investigate activation status of PKCα, PI3K, PDPK1 and PLC-γ and protein levels of PP2A and DAG to explore their potential roles in the formation of hypertrophic and nodular PWS lesions. We found phosphorylated levels of PKCα, PI3K, PDPK1, and PLC-γ and protein levels of PP2A and DAG showed moderate increases in the endothelial cells of hypertrophic PWS as compared to the adjacent normal skin. These increases extended throughout the entire stroma of blood vessels in PWS nodules. Many proliferating cells, such as fibroblasts, also showed strong activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulations of PP2A and DAG in nodular PWS lesions. Our data showed that there is aberrant activation of PKCα, PI3K, PDPK1 and PLC-γ and upregulation of PP2A and DAG mainly in endothelial cells in hypertrophic PWS areas, but presenting in the entire vasculatures and surrounding fibroblasts in PWS nodules. Our data suggest that both PKCα and PI3K signaling pathways contribute to the development of hypertrophy and nodularity in adult PWS.

The Role of Laser Speckle Imaging in Port-Wine Stain Research: Recent Advances and Opportunities.

Here, we review our current knowledge on the etiology and treatment of port-wine stain (PWS) birthmarks. Current treatment options have significant limitations in terms of efficacy. With the combination of 1) a suitable preclinical microvascular model, 2) laser speckle imaging (LSI) to evaluate blood-flow dynamics, and 3) a longitudinal experimental design, rapid preclinical assessment of new phototherapies can be translated from the lab to the clinic. The combination of photodynamic therapy (PDT) and pulsed-dye laser (PDL) irradiation achieves a synergistic effect that reduces the required radiant exposures of the individual phototherapies to achieve persistent vascular shutdown. PDL combined with anti-angiogenic agents is a promising strategy to achieve persistent vascular shutdown by preventing reformation and reperfusion of photocoagulated blood vessels. Integration of LSI into the clinical workflow may lead to surgical image guidance that maximizes acute photocoagulation, is expected to improve PWS therapeutic outcome. Continued integration of noninvasive optical imaging technologies and biochemical analysis collectively are expected to lead to more robust treatment strategies.

Sustained activation of c-Jun N-terminal and extracellular signal-regulated kinases in port-wine stain blood vessels.

BACKGROUND: Port-wine stain (PWS) is a congenital, progressive vascular malformation but the pathogenesis remains incompletely understood. OBJECTIVE: We sought to investigate the activation status of various kinases, including extracellular signal-regulated kinase, c-Jun N-terminal kinase, AKT, phosphatidylinositol 3-kinase, P70 ribosomal S6 kinase, and phosphoinositide phospholipase C γ subunit, in PWS biopsy tissues. METHODS: Immunohistochemistry was performed on 19 skin biopsy samples from 11 patients with PWS. RESULTS: c-Jun N-terminal kinase, extracellular signal-regulated kinase, and P70 ribosomal S6 kinase in pediatric and adult PWS blood vessels were consecutively activated. Activation of AKT and phosphatidylinositol 3-kinase was found in many adult hypertrophic PWS blood vessels but not in infants. Phosphoinositide phospholipase C γ subunit showed strong activation in nodular PWS blood vessels. LIMITATION: Infantile PWS sample size was small. CONCLUSION: Our data suggest a subsequent activation profile of various kinases during different stages of PWS: (1) c-Jun N-terminal and extracellular signal-regulated kinases are firstly and consecutively activated in all PWS tissues, which may contribute to both the pathogenesis and progressive development of PWS; (2) AKT and phosphatidylinositol 3-kinase are subsequently activated, and are involved in the hypertrophic development of PWS blood vessels; and (3) phosphoinositide phospholipase C γ subunit is activated in the most advanced stage of PWS and may participate in nodular formation.

Topical rapamycin systematically suppresses the early stages of pulsed dye laser-induced angiogenesis pathways.

BACKGROUND: Administration of topical rapamycin (RPM) suppresses the regeneration and revascularization of photocoagulated blood vessels induced by pulsed dye laser (PDL). OBJECTIVE: To systematically elucidate the molecular pathophysiology of the inhibition of PDL-induced angiogenesis by topical RPM in a rodent model. METHODS: The mRNA expression profiles of 86 angiogenic genes and phosphorylation levels of ribosomal protein S6 kinase (P70S6K) in rodent skin were examined with or without topical RPM administration post-PDL exposure. RESULTS: The PDL-induced systematic increases in transcriptional levels of angiogenic genes showed a peak expression at days 3-7 post-PDL in rodent skin. Topical application of 1% RPM significantly and systematically suppressed the PDL-induced increase in mRNA levels of the examined angiogenic genes during the first five days post-PDL. The phosphorylation levels of P70S6K increased after PDL exposure but those increases were suppressed by the topical RPM. After topical application, RPM penetrated to an approximate depth of 768.4 µm into rodent skin. CONCLUSION: Topical application of 1% RPM can significantly and systematically suppress the PDL-induced early stage of angiogenesis via inhibition of the AKT/mTOR/P70S6K pathway in a rodent model.

The optical property of core-shell nanosensors and detection of atrazine based on localized surface plasmon resonance (LSPR) sensing.

Three different nanosensors with core-shell structures were fabricated by molecular self-assembly and evaporation techniques. Such closely packed nanoparticles exhibit fine optical properties which are useful for biochemical sensing. The refractive index sensitivity (RIS) of nanosensors was detected by varying the refractive index of the surrounding medium and the decay length of nanosensors was investigated using a layer-by-layer polyelectrolyte multilayer assembly. The results showed that the thickness of the Au shell plays an important role in determining the RIS and the decay length. A system based on localized surface plasmon resonances (LSPR) sensing was constructed in our study. The core-shell nanosensors can detect 10 ng/mL atrazine solutions and are suitable for pesticide residue detection.

Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials.

Chlorogenic acid (CGA) is a type of polyphenol compound found in rich concentrations in many plants such as green coffee beans. As an active natural substance, CGA exerts diverse therapeutic effects in response to a variety of pathological challenges, particularly conditions associated with chronic metabolic diseases and age-related disorders. It shows multidimensional functions, including neuroprotection for neurodegenerative disorders and diabetic peripheral neuropathy, anti-inflammation, anti-oxidation, anti-pathogens, mitigation of cardiovascular disorders, skin diseases, diabetes mellitus, liver and kidney injuries, and anti-tumor activities. Mechanistically, its integrative functions act through the modulation of anti-inflammation/oxidation and metabolic homeostasis. It can thwart inflammatory constituents at multiple levels such as curtailing NF-kB pathways to neutralize primitive inflammatory factors, hindering inflammatory propagation, and alleviating inflammation-related tissue injury. It concurrently raises pivotal antioxidants by activating the Nrf2 pathway, thus scavenging excessive cellular free radicals. It elevates AMPK pathways for the maintenance and restoration of metabolic homeostasis of glucose and lipids. Additionally, CGA shows functions of neuromodulation by targeting neuroreceptors and ion channels. In this review, we systematically recapitulate CGA's pharmacological activities, medicinal properties, and mechanistic actions as a potential therapeutic agent. Further studies for defining its specific targeting molecules, improving its bioavailability, and validating its clinical efficacy are required to corroborate the therapeutic effects of CGA.