The anti-inflammatory activity of flavonoids and alkaloids from Sophora flavescens alleviates psoriasiform lesions: Prenylation and methoxylation beneficially enhance bioactivity and skin targeting.

The herb Sophora flavescens displays anti-inflammatory activity and can provide a source of antipsoriatic medications. We aimed to evaluate whether S. flavescens extracts and compounds can relieve psoriasiform inflammation. The ability of flavonoids (maackiain, sophoraflavanone G, leachianone A) and alkaloids (matrine, oxymatrine) isolated from S. flavescens to inhibit production of cytokine/chemokines was examined in keratinocytes and macrophages. Physicochemical properties and skin absorption were determined by in silico molecular modeling and the in vitro permeation test (IVPT) to establish the structure-permeation relationship (SPR). The ethyl acetate extract exhibited higher inhibition of interleukin (IL)-6, IL-8, and CXCL1 production in tumor necrosis factor-α-stimulated keratinocytes compared to the ethanol and water extracts. The flavonoids demonstrated higher cytokine/chemokine inhibition than alkaloids, with the prenylated flavanones (sophoraflavanone G, leachianone A) led to the highest suppression. Flavonoids exerted anti-inflammatory effects via the extracellular signal-regulated kinase, p38, activator protein-1, and nuclear factor-κB signaling pathways. In the IVPT, prenylation of the flavanone skeleton significantly promoted skin absorption from 0.01 to 0.22 nmol/mg (sophoraflavanone G vs. eriodictyol). Further methoxylation of a prenylated flavanone (leachianone A) elevated skin absorption to 2.65 nmol/mg. Topical leachianone A reduced the epidermal thickness in IMQ-treated mice by 47%, and inhibited cutaneous scaling and cytokine/chemokine overexpression at comparable levels to a commercial betamethasone product. Thus, prenylation and methoxylation of S. flavescens flavanones may enable the design of novel antipsoriatic agents.

Topically applied pH-responsive nanogels for alkyl radical-based therapy against psoriasiform hyperplasia.

Phototherapy is a conventional antipsoriatic approach based on oxygen-relevant generation of oxidative stress to inhibit keratinocyte hyperproliferation. However, this therapy can be restricted due to local hypoxia in psoriatic lesions. The generation of alkyl radicals is oxygen-independent and suppresses hyperproliferation. Herein, we established alkyl radical-based therapy to treat psoriatic hyperplasia. Because alkyl radicals are short-lived compounds, we loaded 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) as a precursor of alkyl radicals into the chitosan nanogels to improve stability. The present study presented a topically applied nanogel that led to a pH-responsive network sensitive to skin pH. This pH responsiveness of the nanogels allowed fast alkyl radical release in the target site. The physicochemical properties of the prepared nanogels were determined through size, zeta potential, scanning electron microscopy, and absorption spectroscopy. The antipsoriatic activity was examined with keratinocyte- and animal-based studies. The nanogels displayed a smooth and spherical morphology with a hydrodynamic diameter of 215 nm. This size was largely increased as the environmental pH increased to 6. The nanogels heated at 44 °C produced alkyl radicals to induce keratinocyte death through the necrosis pathway. Bioimaging demonstrated that topically applied nanogels could deliver alkyl radicals into the epidermis. This targeting was accompanied by the accumulation of free radicals in the epidermis according to the 2',7'-dichlorodihydrofluorescein diacetate assay. The imiquimod-stimulated psoriasiform animal model indicated a remarkable reduction in erythema, scaling, and overexpressed cytokines upon topical treatment of the nanogels. The transepidermal water loss of the psoriasiform skin was inhibited from 51.7 to 27.0 g/m2/h, suggesting barrier function recovery by the nanocarriers. The nanogels lowered hyperplasia by decreasing the epidermal thickness from 212 to 89 µm. The incorporation of 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) as a pH-sensitive fluorescence dye in the nanogels could be used to diagnose the severity of the psoriasiform plaque due to the stronger fluorescence of HPTS in skin with lower pH (psoriasiform skin pH = 4.4) than in healthy skin (pH = 4.9). It was possible to deliver the prepared nanogels into the epidermis to restrain hyperplasia without causing cutaneous irritation.

Discrimination of Traditional Chinese Medicine Syndromes in Type 2 Diabetic Patients Based on Metabolomics-Proteomics Profiles.

Materials and Methods: The metabolomics-proteomics of sixty patients with T2DM were acquired by high-performance liquid chromatography (HPLC). In addition, some clinical features, containing total cholesterol (TC), triglycerides (TG), hemoglobin A1c (HbA1c), body mass index (BMI), and low-density lipoprotein (LDL) together with high-density lipoprotein (HDL), were determined via clinical detection strategies. Abundant metabolites and proteins, respectively, were identified with the analysis of liquid chromatography tandem mass spectrometry (LC-MS/MS). Results: 22 differentially abundant metabolites and 15 differentially abundant proteins were determined. The analysis of bioinformatics suggested that the differentially abundant proteins were commonly associated with the renin-angiotensin system, vitamin digestion and absorption, hypertrophic cardiomyopathy, and so on. Furthermore, differentially abundant metabolites were amino acids and were associated with the biosynthesis of CoA and pantothenate, together with the metabolisms of phenylalanine, beta-alanine, proline, and arginine. Combination analysis revealed that the vitamin metabolism pathway was predominantly affected. Conclusions: DHS syndrome can be separated by certain metabolic-proteomic differences, and metabolism is particularly prominent, especially in vitamin digestion and absorption. From the molecular level, we provide preliminary data for the extensive application of TCM in the study of T2DM, and at the same time benefited in a sense diagnosis and treatment of T2DM.

Formononetin improves the inflammatory response and bone destruction in knee joint lesions by regulating the NF-kB and MAPK signaling pathways.

Formononetin (FMN) is a phytoestrogen that belongs to the isoflavone family. It has antioxidant and anti-inflammatory effects, as well as, many other biological activities. Existing evidence has aroused interest in its ability to protect against osteoarthritis (OA) and promote bone remodeling. To date, research on this topic has not been thorough and many issues remain controversial. Therefore, the purpose of our study was to explore the protective effect of FMN against knee injury and clarify the possible molecular mechanisms. We found that FMN inhibited osteoclast formation induced by receptor activator of NF-κB ligand (RANKL). Inhibition of the phosphorylation and nuclear translocation of p65 in the NF-κB signaling pathway plays a role in this effect. Similarly, during the inflammatory response of primary knee cartilage cells activated by IL-1ß, FMN inhibited the NF-κB signaling pathway and the phosphorylation of the ERK and JNK proteins in the MAPK signaling pathway to suppress the inflammatory response. In addition, in vivo experiments showed that both low- and high-dose FMN had a clear protective effect against knee injury in the DMM (destabilization of the medial meniscus) model, and the therapeutic effect of high-dose FMN was stronger. In conclusion, these studies provide evidence of the protective effect of FMN against knee injury.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

Using Herbal-Cake-Separated Moxibustion for the Treatment of Rats with Chronic Renal Failure.

In the process of moxibustion in clinical practice, subjects need to be in a stable mood and comfortable posture to avoid problems such as moxa ash falling, scalding skin, and poor curative effect. Such problems also exist in the rat moxibustion experiment. To simulate clinical practice, it is necessary to introduce an experimental instrument in animal experiments, that is, a moxibustion device with fixed rats and moxibustion treatment synchronization, which can make experimental rats receive moxibustion treatment quietly and comfortably under non-anesthesia. Our research group designed a rat moxibustion experimental platform. The device was framed by a wooden board with a supporting base plate, multiple fixed components, and partitioned components. The device can achieve the operation mode of moxibustion in rats without binding, avoiding anesthesia and scalding and simultaneously exposing multiple acupoints on the back. This operation can avoid physical and mental injury to rats and operators, which improves the research efficiency and further promotes the development and research of moxibustion animal experiments. The device has a simple structure, is easy to operate and popularize, is comprehensively and innovatively designed, reusable, and is suitable for rat experiments mainly based on moxibustion. This article mainly introduces the structure of the experimental platform device for rat moxibustion, the basic procedure of herbal-cake-separated-moxibustion in experimental rats using the device and describes the establishment of a rat model of chronic renal failure (CRF) and representative experimental results.

Therapeutic efficacy of Scutellaria baicalensis Georgi against psoriasis-like lesions via regulating the responses of keratinocyte and macrophage.

Psoriasis is a chronic and recurrent skin problem that affects 3% of the global population. Nowadays, most medicines may not promise a complete cure for patients with psoriasis because of the development of pharmacoresistance and the side effects of drugs due to the microenvironment impact in the context of skin imbalance. Herein, we attempt to explore the pharmaceutical efficacy of Scutellaria baicalensis (S. baicalensis) in modulating the microenvironment created by macrophages and keratinocytes in psoriasis. The results indicated that treatment of S. baicalensis extract significantly reduced the thickness of epidermis and attenuated psoriatic lesions. Moreover, S. baicalensis extract obviously inhibited the activation and infiltration of macrophages by alleviating inflammatory factors such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and cyclooxygenase-2 (COX-2). The administration of S. baicalensis extract also remarkably abolished oxidative damage upon DNA and proteins, which attributed to the activation of nuclear factor erythroid 2-related factor-2 (Nrf2) and heme oxygenase-1 (HO-1). The network analysis of redox proteomics and cytokine profiles suggested that S. baicalensis administration regulated the specific pathways associated with oxidative stress, inflammation and cytokine signaling cascades to ameliorate the macrophage-targeted responses and subsequently arrest proliferation of keratinocytes. Collectively, our findings highlighted the importance of S. baicalensis application in reprogramming microenvironment to provide an alternative and complementary intervention for long-term psoriatic therapy.

Polydopamine/IR820 nanoparticles as topical phototheranostics for inhibiting psoriasiform lesions through dual photothermal and photodynamic treatments.

Dual photothermal and photodynamic therapy (PTT and PDT) is an attractive approach that generates a synergistic effect for inhibiting keratinocyte hyperproliferation in the treatment of psoriasis. Here, we developed phototheranostic nanocarriers capable of producing hyperthermia and reactive oxygen species (ROS) in response to near-infrared (NIR) illumination. To this end, IR820 with photothermal and photodynamic features was embedded in nano-sized polydopamine (PDA) acting as a PTT agent. A comprehensive characterization of the PDA/IR820 nanosystem was performed according to its morphology, size, zeta potential, UV absorbance, and heat generation. Its therapeutic efficacy was assessed by a keratinocyte-based study and using an imiquimod (IMQ)-stimulated psoriasiform murine model. PDA/IR820 nanoparticles were facilely internalized into keratinocytes and mainly resided in lysosomes. Upon irradiation with NIR light, ROS were generated inside the keratinocytes to cause a photodynamic effect. The live/dead cell assay and cytotoxicity assay demonstrated that PDA and IR820 acted as effective photoabsorbers to induce keratinocyte death. The highest cytotoxic effect was detected in the group of NIR-irradiated PDA/IR820 nanoparticles, which killed 52% of keratinocytes. The nanosystem acted through the caspase and poly ADP-ribose polymerase (PARP) pathways to induce keratinocyte apoptosis. In vitro and in vivo skin permeation indicated the selective accumulation of the topically applied PDA/IR820 nanoparticles within psoriasiform skin, suggesting their skin-targeting capability. The combination of PDA/IR820 nanoparticles and NIR irradiation increased the skin temperature by 11.7 °C. PTT/PDT eliminated psoriasiform plaques in mice by decreasing hyperplasia, inhibiting cytokine overexpression, and recovering the barrier function. The epidermal thickness of the IMQ-treated skin was reduced from 134 to 34 µm by the nanocarriers plus NIR. The IR820 nanoparticles were largely deposited on the inflamed areas of psoriasiform lesions for monitoring the severity of inflammation. The image-guided phototheranostic nanoparticles showed their potential for applications in psoriasis management via noninvasive topical administration.

Nanoencapsulation of Tea Catechins for Enhancing Skin Absorption and Therapeutic Efficacy.

Tea catechins are a group of flavonoids that show many bioactivities. Catechins have been extensively reported as a potential treatment for skin disorders, including skin cancers, acne, photoaging, cutaneous wounds, scars, alopecia, psoriasis, atopic dermatitis, and microbial infection. In particular, there has been an increasing interest in the discovery of cosmetic applications using catechins as the active ingredient because of their antioxidant and anti-aging activities. However, active molecules with limited lipophilicity have difficulty penetrating the skin barrier, resulting in low bioavailability. Nevertheless, topical application is a convenient method for delivering catechins into the skin. Nanomedicine offers an opportunity to improve the delivery efficiency of tea catechins and related compounds. The advantages of catechin-loaded nanocarriers for topical application include high catechin loading efficiency, sustained or prolonged release, increased catechin stability, improved bioavailability, and enhanced accumulation or targeting to the nidus. Further, various types of nanoparticles, including liposomes, niosomes, micelles, lipid-based nanoparticles, polymeric nanoparticles, liquid crystalline nanoparticles, and nanocrystals, have been employed for topical catechin delivery. These nanoparticles can improve catechin permeation via close skin contact, increased skin hydration, skin structure disorganization, and follicular uptake. In this review, we describe the catechin skin delivery approaches based on nanomedicine for treating skin disorders. We also provide an in-depth description of how nanoparticles effectively improve the skin absorption of tea catechins and related compounds, such as caffeine. Furthermore, we summarize the possible future applications and the limitations of nanocarriers for topical delivery at the end of this review article.

Acid Water-ground Nano-realgar Is Superior to Crude Realgar in Promoting Apoptosis of MCF-7 Breast Cancer Cells.

OBJECTIVE: Realgar is a traditional mineral Chinese medicine with antitumor effects, but it has high toxicity and low efficacy in its crude form. The purpose of this study was to optimize realgar to increase its efficacy and therapeutic potential. METHODS: Crude realgar (CR) was mechanically ground to obtain nano-realgar (NR), and then nano-realgar processed products (NRPPs) were obtained using three different traditional Chinese medicine processing methods: grinding in water, acid water, and alkali water, respectively. RESULTS: By analyzing the size distribution of nanoparticles and the content of arsenic trioxide (As2O3; ATO), we found that acid water-ground NRPPs had the characteristics of high purity and low toxicity. The effects of CR, NR, and NRPPs on proliferation, cell cycle, and apoptosis of MCF-7 cells were detected, and the ability of NRPPs to induce apoptosis in MCF-7 cells was analyzed. The results showed that the average particle size of acid water-ground NRPPs was 137.7 nm, and the content of ATO was 2.83 mg/g. Acid water-ground NRPPs showed better effects on inhibiting proliferation, cell cycle, and apoptosis of MCF-7 cells than CR and NR. Western blot assays further confirmed that acid water-ground NRPPs upregulated the protein expression of TP53, Bax, cytochrome c, caspase-9, and caspase-3 in MCF-7 cells (P<0.05) and inhibited the expression of Bcl-2 (P<0.05). CONCLUSION: These results suggest that acid water-ground NRPPs can induce apoptosis of MCF-7 cells through regulating mitochondrial-mediated apoptosis, providing evidence for the clinical application of realgar.

Rhubarb hydroxyanthraquinones act as antiobesity agents to inhibit adipogenesis and enhance lipolysis.

Rhubarb as an herbal medicine has been shown to exhibit antiadipogenic activity. This study evaluated and compared the lipid-lowering activity of five rhubarb hydroxyanthraquinones (HAQs), including chrysophanol, aloe emodin, emodin, physcion, and rhein, aiming to identify candidate compounds for obesity treatment. Examination of the antiobesity effects of HAQs in 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese rats showed that these anthraquinone compounds inhibited lipid accumulation in 3T3-L1 cells before and after differentiation. Emodin and rhein showed greater inhibition than the other compounds; dosage at 50 µM reduced intracellular triglyceride (TG) by about 30% in the differentiated adipocytes. Both compounds also revealed lipolytic effects to increase glycerol release from adipocytes. Adipokine overexpression induced by differentiation was downregulated by emodin and rhein through mitogen-activated protein kinase (MAPK) signaling. Despite their structural similarity, emodin and rhein exhibited different mechanisms on adipogenesis and lipid metabolism. Rhein restrained lipid deposition by controlling adipogenic transcriptional factors and lipolytic lipases during differentiation. The lipid-lowering effects of emodin did not use these pathways but reduced levels of lipogenic enzymes. HFD consumption in rats significantly increased body weight, visceral fat mass and adipocyte size, which were attenuated by intraperitoneal delivery of emodin or rhein. Rhein showed greater amelioration of obesity than emodin, decreasing plasma cholesterol by 29% and 14%, respectively. HAQs also suppressed cytokine upregulation in the liver and adipose tissues of obese rats. Rhein is a potential antiobesity agent through its ability to regulate obesity-associated adipogenesis, lipolysis and inflammation.

The Demethoxy Derivatives of Curcumin Exhibit Greater Differentiation Suppression in 3T3-L1 Adipocytes Than Curcumin: A Mechanistic Study of Adipogenesis and Molecular Docking.

Curcumin is a known anti-adipogenic agent for alleviating obesity and related disorders. Comprehensive comparisons of the anti-adipogenic activity of curcumin with other curcuminoids is minimal. This study compared adipogenesis inhibition with curcumin, demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC), and their underlying mechanisms. We differentiated 3T3-L1 cells in the presence of curcuminoids, to determine lipid accumulation and triglyceride (TG) production. The expression of adipogenic transcription factors and lipogenic proteins was analyzed by Western blot. A significant reduction in Oil red O (ORO) staining was observed in the cells treated with curcuminoids at 20 µM. Inhibition was increased in the order of curcumin < DMC < BDMC. A similar trend was observed in the detection of intracellular TG. Curcuminoids suppressed differentiation by downregulating the expression of peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), leading to the downregulation of the lipogenic enzymes acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS). AMP-activated protein kinase α (AMPKα) phosphorylation was also activated by BDMC. Curcuminoids reduced the release of proinflammatory cytokines and leptin in 3T3-L1 cells in a dose-dependent manner, with BDMC showing the greatest potency. BDMC at 20 µM significantly decreased leptin by 72% compared with differentiated controls. Molecular docking computation indicated that curcuminoids, despite having structural similarity, had different interaction positions to PPARγ, C/EBPα, and ACC. The docking profiles suggested a possible interaction of curcuminoids with C/EBPα and ACC, to directly inhibit their expression.

Recent advances in herbal combination nanomedicine for cancer: delivery technology and therapeutic outcomes.

Introduction: The use of herbal compounds in cancer therapy has great potential to promote the efficacy of current cancer therapeutic strategies. Herbal compounds were successfully reported to enhance tumor cells sensitization to the action of chemo-, hormonal- and gene-therapeutic agents via different mechanisms. Herbal ingredients can affect different signaling pathways, reduce the toxic side effects or inhibit the efflux of anticancer drugs.Areas covered: This review will discuss the delivery of herbal compounds with other cancer treatments such as hormonal, small molecule inhibitors and inorganic hybrids to tumor cells. An overview of physicochemical properties of herbal components that require intelligent design of combo-nanomedicines for efficient co-delivery of those herbal-derived and other anticancer agents was discussed. Nanocarriers provide various benefits to overcome the shortcomings of the encapsulated herbal compounds including improved solubility, increased stability and enhanced tumor targeting. Different nanocarrier systems were the focus of this review.Expert opinion: Multifunctional nanocarrier systems encapsulating herbal and different anticancer drugs showed to be a wonderful approach in the treatment of cancer enabling the co-delivery of anticancer drugs with versatile modes of action in an accurate manner in an attempt to enhance the efficacy, benefit from the synergism between the drugs as well as to minimize the development of multi-drug resistance. The main challenge point is the early detection and management of any developed adverse effect.

Photothermal treatment by PLGA-gold nanorod-isatin nanocomplexes under near-infrared irradiation for alleviating psoriasiform hyperproliferation.

Psoriasis is a chronic autoimmune skin disorder that involves keratinocyte hyperproliferation and inflammatory cell recruitment. A strategy to mitigate psoriatic lesions is to induce keratinocyte apoptosis for proliferation suppression. Herein we designed a nanoformulation capable of treating psoriasis via hyperthermia-induced apoptosis in response to near-infrared (NIR) irradiation. To this end, gold nanorods (GNRs) and isatin, which is an anti-inflammatory agent for synergizing antipsoriatic activity, were loaded into a poly (lactic-co-glycolic acid) (PLGA) matrix to form the nanocomplexes. The physicochemical and photothermal properties of the nanocomplexes were determined in terms of size, surface charge, NIR-absorbing feature, isatin release, keratinocyte uptake, and cytotoxicity. The nanocomplexes showed a spherical shape with an average size of about 180 nm. The GNR-loaded nanoparticles can efficiently convert NIR light at 0.42 W/cm2 into heat with an increased temperature of 10 °C. When combined with NIR exposure, the nanocomplexes were internalized into keratinocyte cytoplasm with an inhibition of keratinocyte viability to about 60%. Live/dead cell assay and flow cytometry confirmed that the nanocomplexes could serve as NIR-absorbers to specifically elicit keratinocyte apoptosis through caspase and poly ADP-ribose polymerase (PARP) pathways. The in vivo psoriasiform murine model indicated that the combined nanocomplexes and NIR inhibited epidermal hyperplasia and neutrophil infiltration. The overexpressed cytokines in the lesion could be recovered to normal baseline level after the photothermal management. The subcutaneous nanocomplexes remained in the skin for at least 5 days. The nanocomposites produced a negligible toxicity in the skin or liver of healthy mice. The photothermal nanosystems, as designed in this study, shed new light on the therapeutic approach against psoriasis.

Multifunctional TiO2/SBA-15 mesoporous silica hybrids loaded with organic sunscreens for skin application: The role in photoprotection and pollutant adsorption with reduced sunscreen permeation.

TiO2 acts as an inorganic sunscreen and photocatalyst to protect humans from environmental pollutants. We incorporated TiO2 into mesoporous silica (SBA-15) for skin application to prevent environmental stresses including UVA irradiation and pollutant invasion. Organic ultraviolet (UV)A filters such as avobenzone and oxybenzone were then loaded into mesoporous support for synergistic sunscreen efficiency. The as-prepared formulations with different TiO2 amounts (10 %-50 %) were fabricated. The pore size decreased from 4.72 to 4.00 nm following the increase in TiO2 percentage. TiO2/SBA-15 captured about 60 % fluoranthene and 80 % furfural within 3 h with no significant difference due to different TiO2 content. The in vitro photoprotection assessed by UVA/UVB ratio exhibited the increase in Boots star rating from 2 to 3 to 5 by entrapment of avobenzone into TiO2/SBA-15. Thirty-percent TiO2/SBA-15 in hydrogel decreased avobenzone and oxybenzone deposition by 70 % and 80 % compared to free form, respectively. Avobenzone and TiO2 supplementation to SBA-15 significantly alleviated skin cell death and neutrophil recruitment in the photoaged mouse skin compared to the SBA-15 application alone. Compared to the UVA-irradiated skin, 30 % TiO2/SBA-15 showed a 2.5- and 3.1-fold decline in IL-1ß and IL-6 levels, respectively. The TiO2/SBA-15 hybrid was considered non-irritant based on results of cytotoxicity assay, skin histology, and cutaneous barrier function. Our data indicate that the versatile mesoporous silica is an effective system for topical use in sunscreen and skin protection.

Multifunctional lipid-based nanocarriers with antibacterial and anti-inflammatory activities for treating MRSA bacteremia in mice.

BACKGROUND: Bacteremia-induced sepsis is a leading cause of mortality in intensive care units. To control a bacterial infection, an immune response is required, but this response might contribute to organ failure. Kidneys are one of the main organs affected by bacteremia. Combination therapies with antibacterial and anti-inflammatory effects may be beneficial in treating bacteremia. This study aimed to develop nanostructured lipid carriers (NLCs) loaded with ciprofloxacin and rolipram that exert a combination of anti-methicillin-resistant Staphylococcus aureus (MRSA) and anti-inflammatory effects. Retinol was incorporated into the nanoparticles to transport retinol-binding protein 4 (RBP4) to the kidneys, which abundantly express RBP receptors. The NLCs were fabricated by high-shear homogenization and sonication, and neutrophils were used as a model to assess their anti-inflammatory effects. Mice were injected with MRSA to establish a model of bacteremia with organ injury. RESULTS: The mean nanoparticle size and zeta potential of the NLCs were 171 nm and - 39 mV, respectively. Ciprofloxacin (0.05%, w/v) and rolipram (0.02%) achieved encapsulation percentages of 88% and 96%, respectively, in the nanosystems. The minimum bactericidal concentration of free ciprofloxacin against MRSA increased from 1.95 to 15.63 µg/ml when combined with rolipram, indicating a possible drug-drug interaction that reduced the antibacterial effect. Nanoparticle inclusion promoted the anti-MRSA activity of ciprofloxacin according to time-kill curves. The NLCs were found to be largely internalized into neutrophils and exhibited superior superoxide anion inhibition than free drugs. Retinol incorporation into the nanocarriers facilitated their efficient targeting to the kidneys. The NLCs significantly mitigated MRSA burden and elastase distribution in the organs of MRSA-infected animals, and the greatest inhibition was observed in the kidneys. Bacterial clearance and neutrophil infiltration suppression attenuated the bacteremia-induced cytokine overexpression, leading to an improvement in the survival rate from 22% to 67%. CONCLUSIONS: The dual role of our NLCs endowed them with greater efficacy in treating MRSA bacteremia than that of free drugs.

Low-fluence laser-facilitated platelet-rich plasma permeation for treating MRSA-infected wound and photoaging of the skin.

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Unprecedented tibial bone lengthening of 33.5 cm by distraction osteogenesis for the reconstruction of a subtotal tibial bone defect. A case report and literature review.

BACKGROUND: We present a case of an immense unprecedented tibial bone lengthening of 33.5 cm. The management of chronic osteomyelitis of the right tibia with subtotal tibial bone defect, talus defect and equinus ankle deformity. We demonstrate limb reconstruction by distraction osteogenesis and correction of ankle deformity with the Ilizarov technique. Limb salvage was preferred as an alternative to amputation to restore basic limb function. CASE PRESENTATION: A 16-year-old male patient fell and injured his right lower leg. He attempted to treat the symptoms with traditional home remedies. During 15 months of self-treating, he developed osteomyelitis of the right tibia and had lost function in his foot. Radiology revealed immense bone defect of the right tibia, including talus bone defect and equinus deformity of the calcaneus. The patient's right tibia was non weight-bearing, had drainage sinus just below his knee and a large scar anteriorly along the entire length of the tibia. CONCLUSION: Upon completion of treatment, the patient was able to avoid amputation of his leg with partially restored function for weight-bearing. He carried himself without assistance after 3 years of lost function in his right leg. Tibial bone distraction osteogenesis of 33.5 cm was done after 90% of the tibial length was defected. To the best of our best knowledge, this case is one of a kind to achieve distraction of tibial bone to such length.

Bioactive Agent Discovery from the Natural Compounds for the Treatment of Type 2 Diabetes Rat Model.

Diabetes mellitus is a well-known chronic metabolic disease that poses a long-term threat to human health and is characterized by a relative or absolute lack of insulin, resulting in hyperglycemia. Type 2 diabetes mellitus (T2DM) typically affects many metabolic pathways, resulting in ß-cell dysfunction, insulin resistance, abnormal blood glucose levels, inflammatory processes, excessive oxidative reactions, and impaired lipid metabolism. It also leads to diabetes-related complications in many organ systems. Antidiabetic drugs have been approved for the treatment of hyperglycemia in T2DM; these are beneficial for glucose metabolism and promote weight loss, but have the risk of side effects, such as nausea or an upset stomach. A wide range of active components, derived from medicinal plants, such as alkaloids, flavonoids, polyphenol, quinones, and terpenoids may act as alternative sources of antidiabetic agents. They are usually attributed to improvements in pancreatic function by increasing insulin secretions or by reducing the intestinal absorption of glucose. Ease of availability, low cost, least undesirable side effects, and powerful pharmacological actions make plant-based preparations the key player of all available treatments. Based on the study of therapeutic reagents in the pathogenesis of humans, we use the appropriate animal models of T2DM to evaluate medicinal plant treatments. Many of the rat models have characteristics similar to those in humans and have the advantages of ease of genetic manipulation, a short breeding span, and access to physiological and invasive testing. In this review, we summarize the pathophysiological status of T2DM rat models and focus on several bioactive compounds from herbal medicine with different functional groups that exhibit therapeutic potential in the T2DM rat models, in turn, may guide future approach in treating diabetes with natural drugs.

Intramedullary reaming and irrigation and antibiotic-loaded calcium sulfate implantation for the treatment of infection after intramedullary nailing: a retrospective study of 19 cases.

BACKGROUND: The incidence of intramedullary infection is increasing with increased use of intramedullary fixation for long bone fractures. However, appropriate treatment for infection after intramedullary nailing is unclear. The purpose of this study was to report the results of our treatment protocol for infection after intramedullary nailing: intramedullary nail removal, local debridement, reaming and irrigation, and antibiotic-loaded calcium sulfate implantation with or without segmental bone resection and distraction osteogenesis. METHODS: We retrospectively reviewed the records of patients with an infection after intramedullary nailing treated from 2014 to 2017 at our center. Patients with follow-up of less than 24 months, received other treatment methods, or those with serious medical conditions were excluded from the analysis. Patients met the criteria were treated as described above, followed by distraction osteogenesis in 9 cases to repair bone defect. The infection remission rate, infection recurrence rate, and post-operative complication rates were assessed. RESULTS: A total of 19 patients were included in the analysis. All of patients had satisfactory outcomes with an average follow-up of 38.1 ± 9.4 months (range, 24 to 55 months). Eighteen patients (94.7%) achieved infection remission; 1 patient (5.3%) developed a reinfection that resolved after repeat debridement. Nine patients with bone defects (average size 4.7 ± 1.3 cm; range, 3.3 to 7.6 cm) were treated with bone transport which successfully restored the length of involved limb. The mean bone transport duration was 10.7 ± 4.0 months (range, 6.7 to 19.5 months). The majority of patients achieved full weight bearing and became pain free during the follow-up period. Postoperative complications mainly included prolonged aseptic drainage (7/19; 36.8%), re-fracture (1/19; 5.3%) and joint stiffness, which were successfully managed by regular dressing changes and re-fixation, respectively. CONCLUSION: Intramedullary nail removal, canal reaming and irrigation, and antibiotic-loaded calcium sulfate implantation (with or without distraction osteogenesis) is effective for treating infections after intramedullary nailing.