Spirulina-based carbon materials as adsorbents for drinking water taste and odor control: Removal efficiency and assessment of cyto-genotoxic effects.

The sensory quality of drinking water, and particularly its taste and odor (T&O) is a key determinant of consumer acceptability, as consumers evaluate water by their senses. Some of the conventional treatment processes to control compounds which impart unpleasant T&O have limitations because of their low efficiency and/or high costs. Therefore, there is a great need to develop an effective process for removing T&O compounds without secondary concerns. The primary objective of this study was to assess for the first time the effectiveness of spirulina-based carbon materials in removing geosmin (GSM) and 2-methylisoborneol (2-MIB) from water, two commonly occurring natural T&O compounds. The efficiency of the materials to remove environmentally relevant concentrations of GSM and 2-MIB (ng L-1) from ultrapure and raw water was investigated using a sensitive headspace solid-phase microextraction coupled with gas chromatography mass spectrometry (HS-SPME-GC/MS) method. Moreover, the genotoxic and cytotoxic effects of the spirulina-based materials were assessed for the first time to evaluate their safety and their potential in the treatment of water for human consumption. Based on the results, spirulina-based materials were found to be promising for drinking water treatment applications, as they did not exert geno-cytotoxic effects on human cells, while presenting high efficiency in removing GSM and 2-MIB from water.

[Identification method of 2-methylisoborneol and geosmin in water by purge and trap-gas chromatography-mass spectrometry].

OBJECTIVE: To establishe an analysis and identification method for 2-methylisoborneol(2-MIB) and geosmin(GSM) in water using purge and trap-gas chromatography-mass spectrometry. METHODS: The samples were enriched and analyzed using a purge and trap system, followed by the separation on a DB-624(30 m×0.25 mm, 1.4 µm) chromatographic column. Quantification was performed using gas chromatography-mass spectrometry with the selected ion monitoring and internal standard calibration. RESULTS: The calibration curves for 2-MIB and GSM showed an excellent linearity in the range of 1 to 100 ng/L with R~2 values greater than 0.999. The detection limit and quantification limit for both 2-MIB and GSM were 0.33 ng/L and 1.0 ng/L, respectively. Spike recovery experiments were further carried on the source water and drinking water at three concentration levels. It showed that the average recoveries were from 82.0% to 111.0% for 2-MIB while 84.0% to 110% for GSM. Additionally, the test precision of 2-MIB and GSM ranged from 1.9% to 7.3% and 1.9% to 5.0%(n=6), respectively. The analysis of multiple samples including the local source water, treated water and distribution network water confirmed the existence of 2-MIB and GSM. CONCLUSION: Compared to the national standard(GB/T 5750.8-2023), the proposed method enables fully automated sample introduction and analysis without the extra pre-treatment. It provides the advantages of simplicity, good repeatability and high accuracy.

Contact Allergy to Allergens in the Swedish Baseline Series Overrepresented in Diabetes Patients with Skin Reactions to Medical Devices - A Retrospective Study from Southern Sweden.

Allergic contact dermatitis is reported among individuals using continuous glucose monitoring systems and insulin pumps. The aim of this study was to describe contact allergy patterns for allergens in the Swedish baseline series and medical device-related allergens among users. Contact allergy to baseline series allergens and isobornyl acrylate was compared between diabetes patients and dermatitis patients patch-tested at the Department of Occupational and Environmental Dermatology during 2017 to 2020. Fifty- four diabetes patients and 2,567 dermatitis patients were included. The prevalence of contact allergy to fragrance mix II and sesquiterpene lactone mix was significantly higher in diabetes patients compared with dermatitis patients. Of the diabetes patients 13.0% and of the dermatitis patients 0.5% tested positive to sesquiterpene lactone mix (p < 0.001). Of the diabetes patients 7.4% and of the dermatitis patients 2.3% tested positive to fragrance mix II (p = 0.041). Of the diabetes patients 70.4% tested positive to medical device-related allergens. Of the diabetes patients 63.0% and of the dermatitis patients 0.2% were allergic to isobornyl acrylate (p < 0.001). In conclusion, not only medical device-related contact allergies, but also contact allergy to baseline series allergens (fragrance mix II and sesquiterpene lactone mix), is overrepresented in diabetes patients who use medical devices.

Unpredictable Chemical Diversity of Essential Oils in Cinnamomum burmanni (Lauraceae) Living Collections: Beyond Maternally Inherited Phylogenetic Relationships.

The genus Cinnamomum encompasses diverse species with various applications, particularly in traditional medicine and spice production. This study focuses on Cinnamomum burmanni, specifically on a high-D-borneol-content chemotype, known as the Meipian Tree, in Guangdong Province, South China. This research explores essential oil diversity, chemotypes, and chloroplast genomic diversity among 28 C. burmanni samples collected from botanical gardens. Essential oils were analyzed, and chemotypes classified using GC-MS and statistical methods. Plastome assembly and phylogenetic analysis were conducted to reveal genetic relationships. Results showed distinct chemotypes, including eucalyptol and borneol types, with notable variations in essential oil composition. The chloroplast genome exhibited conserved features, with phylogenetic analysis revealing three major clades. Borneol-rich individuals in clade II suggested a potential maternal inheritance pattern. However, phylogenetic signals revealed that the composition of essential oils is weakly correlated with plastome phylogeny. The study underscores the importance of botanical gardens in preserving genetic and chemical diversity, offering insights for sustainable resource utilization and selective breeding of high-yield mother plants of C. burmanni.

Binding Affinity, Selectivity, and Pharmacokinetics of the Oxytocin Receptor Antagonist L-368,899 in the Coyote (Canis latrans).

L-368,899 is a selective small-molecule oxytocin receptor (OXTR) antagonist originally developed in the 1990s to prevent preterm labor. Although its utility for that purpose was limited, L-368,899 is now one of the most commonly used drugs in animal research for the selective blockade of neural OXTR after peripheral delivery. A growing number of rodent and primate studies have used L-368,899 to evaluate whether certain behaviors are oxytocin dependent. These studies have improved our understanding of oxytocin's function in the brains of rodents and monkeys, but very little work has been done in other mammals, and only a single paper in macaques has provided any evidence that L-368,899 can be detected in the CNS after peripheral delivery. The current study sought to extend those findings in a novel species: coyotes ( Canis latrans ). Coyotes are ubiquitous North American canids that form long-term monogamous pair-bonds. Although monogamy is rare in rodents and primates, all wild canid species studied to date exhibit social monogamy. Coyotes are therefore an excellent model organism for the study of oxytocin and social bonds. Our goal was to determine whether L-368,899 is a viable candidate for future use in behavioral studies in coyotes. We used captive coyotes at the USDA National Wildlife Research Center's Predator Research Facility to evaluate the pharmacokinetics of L-368,899 in blood and CSF during a 90-min time course after intramuscular injection. We then characterized the binding affinity and selectivity of L-368,899 to coyote OXTR and the structurally similar vasopressin 1a receptor. We found that L-368,899 peaked in CSF at 15 to 30 min after intramuscular injection and slowly accumulated in blood. L-368,899 was 40 times more selective for OXTR than vasopressin 1a receptors and bound to the coyote OXTR with an affinity of 12 nM. These features of L-368,899 support its utility in future studies to probe the oxytocin system of coyotes.

Synergistic amelioration between Ligusticum striatum DC and borneol against cerebral ischemia by promoting astrocytes-mediated neurogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: Ligusticum chuanxiong Hort (LCH), with the accepted name of Ligusticum striatum DC in "The Plant List" database, is a widely used ethnomedicine in treating ischemic stroke, and borneol (BO) is usually prescribed with LCH for better therapy. Our previous study confirmed their synergistic effect on neurogenesis against cerebral ischemia. However, the underlying mechanism is still unclear. AIM OF THE STUDY: More and more evidence indicated that astrocytes (ACs) might be involved in the modulation of neurogenesis via polarization reaction. The study was designed to explore the synergic mechanism between LCH and BO in promoting astrocyte-mediated neurogenesis. MATERIALS AND METHODS: After primary cultures and identifications of ACs and neural stem cells (NSCs), the oxygen-glucose deprivation (OGD) model and the concentrations of LCH and BO were optimized. After the OGD-injured ACs were treated by LCH, BO, and their combination, the conditioned mediums were used to culture the OGD-injured NSCs. The proliferation, migration, and differentiation of NSCs were assessed, and the secretions of BDNF, CNTF, and VEGF from ACs were measured. Then the expressions of C3 and PTX3 were detected. Moreover, the mice were performed a global cerebral ischemia/reperfusion model and treated with LCH and (or) BO. After the assessments of Nissl staining, the expressions of Nestin, DCX, GFAP, C3, PTX3, p65 and p-p65 were probed. RESULTS: The most appropriate duration of OGD for the injury of both NSCs and ACs was 6 h, and the optimized concentrations of LCH and BO were 1.30 µg/mL and 0.03 µg/mL, respectively. The moderate OGD environment induced NSCs proliferation, migration, astrogenesis, and neurogenesis, increased the secretions of CNTF and VEGF from ACs, and upregulated the expressions of C3 and PTX3. For the ACs, LCH further increased the secretions of BDNF and CNTF, enhanced PTX3 expression, and reduced C3 expression. Additionally, the conditioned medium from LCH-treated ACs further enhanced NSC proliferation, migration, and neurogenesis. The in vivo study showed that LCH markedly enhanced the Nissl score and neurogenesis, and decreased astrogenesis which was accompanied by downregulations of C3, p-p65, and p-p65/p65 and upregulation of PTX3. BO not only decreased the expression of C3 in ACs both in vitro and in vivo but also downregulated p-p65 and p-p65/p65 in vivo. Additionally, BO promoted the therapeutic effect of LCH for most indices. CONCLUSION: A certain degree of OGD might induce ACs to stimulate the proliferation, astrogenesis, and neurogenesis of NSCs. LCH and BO exhibited a marked synergy in promoting ACs-mediated neurogenesis and reducing astrogenesis, in which LCH played a dominant role and BO boosted the effect of LCH. The mechanism of LCH might be involved in switching the polarization of ACs from A1 to A2, while BO preferred to inhibit the formation of A1 phenotype via downregulating NF-κB pathway.

Improved Quantification of Geosmin and 2-Methylisoborneol in Farmed Fish Using Stable Isotope Dilution Gas Chromatography-Mass Spectrometry.

A requisite to improving the taste and odor attributes of farmed fish is the availability of accurate and practical analytical methods to quantify 2-methylisoborneol (MIB) and geosmin (GSM). Solid-phase microextraction (SPME) enables reliable measurement of nanogram per liter quantities of MIB and GSM in water. In contrast, direct headspace (HS)-SPME of biological matrices with variable proximate compositions can increase bias and uncertainty in off-flavor determinations. Analytical recovery plays a crucial role in the accurate determination of MIB and GSM in fish, and this study investigates strategies to maximize and account for this recovery factor. MIB and GSM values in off-flavor catfish and trout were measured using direct HS-SPME and distillation as sample preparation techniques. Trout samples prepared by distillation yielded 10-fold higher GSM recoveries than those from direct HS-SPME (31% versus 3%). A stable isotope dilution method (SIDM) was implemented by routinely spiking samples with known quantities of deuterium-labeled MIB and GSM, allowing for the correction of sample-to-sample recovery deviations. SIDM-determined GSM values generated recoveries of 106 and 95% for direct HS-SPME and distilled trout, respectively. Aspects of the strategies and techniques presented can be incorporated into existing analytical methods to improve the accuracy and sample throughput. Particularly, routine inclusion of SIDM in the evaluation of MIB and GSM can facilitate identification of reliable practices to control off-flavors in aquaculture.

Borneol serves as an adjuvant agent to promote the cellular uptake of curcumin for enhancing its photodynamic fungicidal efficacy against Candida albicans.

Candida albicans (C. albicans), a major opportunistic pathogenic fungus, is known to cause superficial skin infections. Unfortunately, the misuse of antibiotics has led to the emergence of drug resistance in fungi. Antimicrobial photodynamic therapy (aPDT), a non-antibiotic alternative, has shown potential in treating drug-resistant fungal infections. Curcumin is a photodynamically active phytochemical whose photodynamic fungicidal efficacy is largely dependent on its intracellular accumulation. However, curcumin faces challenges in penetrating the cytoplasm due to its poor water solubility and the fungal cell wall. Borneol, another monoterpenoid phytochemical, is known for its ability to enhance drug absorption. In this study, we showed that borneol improved the cellular uptake of curcumin, thereby enhancing its photodynamic fungicidal efficacy against C. albicans. This effect was attributed to borneol's ability to increase cell permeability. Transcriptomic analysis further confirmed that borneol disrupted the normal structure and function of the C. albicans cell wall and membrane, resulting in dysregulated mRNA expression of related genes and ultimately increased cell permeability. As a result, the excessive accumulation of curcumin in C. albicans triggered the overproduction of intracellular ROS upon exposure to blue light. These excessive intracellular ROS disrupted various cellular structures, interfered with essential cellular processes, inhibited biofilm formation and reduced virulence. Remarkably, borneol was also found to enhance curcumin uptake by C. albicans within biofilms, further enhancing the anti-biofilm efficacy of curcumin-mediated aPDT (Cur-aPDT). In conclusion, the results of this study strongly support the potential of borneol as an adjuvant agent to Cur-aPDT in treating superficial cutaneous fungal infections.

Anti-inflammatory effects and related mechanisms in vitro and in vivo of Hedychium coccineum rhizome essential oil.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedychium coccineum rhizome is an anti-inflammatory ethnomedicine used to remedy inflammation-related swelling and bronchial asthma. AIM OF THE STUDY: The study aimed to analyze the phytochemical constituents of H. coccineum rhizome essential oil (EO) and evaluate its in vitro and in vivo anti-inflammatory effects and underlying mechanisms. MATERIALS AND METHODS: Phytochemical constituents of H. coccineum rhizome EO were analyzed using GC-FID/MS. In RAW264.7 macrophages induced by LPS, blockade of PGE2, NO, IL-1ß, IL-6, and TNF-α secretion by H. coccineum rhizome EO was measured, and then Western blot, qRT-PCR, and immunofluorescent staining were used to evaluate its underlying mechanisms. Moreover, we used the xylene-induced ear edema model for testing anti-inflammatory potential in vivo and examined auricular swelling as well as tissue and serum contents of IL-1ß, IL-6, and TNF-α. RESULTS: EO's main components were E-nerolidol (40.5%), borneol acetate (24.8%), spathulenol (4.5%), linalool (3.8%), elemol (3.5%), and borneol (3.4%). In RAW264.7 cells stimulated by LPS, EO downregulated the expression of pro-inflammatory enzyme (iNOS and COX-2) genes and proteins, thereby suppressing pro-inflammatory mediators (NO and PGE2) secretion. Simultaneously, it reduced TNF-α, IL-1ß, and IL-6 release by downregulating their mRNA expression. Besides, H. coccineum EO attenuated LPS-stimulated activation of NF-κB (by reducing IκBα phosphorylation and degradation to inhibit NF-κB nuclear translocation) and MAPK (by downregulating JNK, p38, and ERK phosphorylation). In xylene-induced mouse ear edema, EO relieved auricular swelling and lowered serum and tissue levels of TNF-α, IL-1ß, and IL-6. CONCLUSIONS: H. coccineum EO had powerful in vivo and in vitro anti-inflammatory effects by inhibiting MAPK and NF-κB activation. Hence, H. coccineum EO should have great potential for application in the pharmaceutical field as a novel anti-inflammatory agent.

New device, 'old' allergens. Allergic contact dermatitis caused by the Dexcom G7 glucose sensor.

BACKGROUND: Allergic contact dermatitis (ACD) has been reported as an adverse effect from the use of several glucose sensors and insulin pumps from different manufacturers. Isobornyl acrylate (IBOA) has been identified as a major culprit sensitizer, but also other acrylates and (modified) colophonium have been reported as causes of ACD. OBJECTIVES: To report the two first cases diagnosed with ACD caused by the Dexcom G7 (DG7) glucose sensor. PATIENTS AND METHODS: Two children with suspected ACD from DG7 were patch tested with our medical device series with an addition of selected test preparations including two variants of modified colophonium - methyl hydrogenated rosinate (MHR) and glyceryl hydrogenated rosinate (GHR). Both patients were also tested with acetone extracts made from different parts of the DG7 sensor. The extracts were analysed by gas chromatography-mass spectrometry (GC-MS). RESULTS: Both patients tested positive to IBOA, hydroabietyl alcohol and GHR. In addition, patient 1 had a positive reaction to MHR and patient 2 had a positive reaction to colophonium. The GC-MS analyses showed the presence of IBOA and colophonium-related substances in the DG7 extracts. CONCLUSIONS: Both patients were diagnosed with contact allergy to well-known medical device-related sensitizers. The presence of IBOA and (modified) colophonium in a newly introduced (on the Swedish market in 2023) glucose sensor is remarkable and indicates an inadequate toxicological assessment of the materials used in the sensor.

Suxiao Jiuxin Pill alleviates myocardial ischemia/reperfusion-induced autophagy via miR-193a-3p/ALKBH5 pathway.

BACKGROUND: Myocardial ischemia/reperfusion injury (MIRI) poses a formidable challenge to cardiac reperfusion therapy due to the absence of effective clinical interventions. Methylation of N6-methyladenosine (m6A), which is the most common post-transcriptional modifications occurring within mammalian mRNA, is believed to be involved in MIRI by modulating autophagy. MicroRNAs (miRNAs) play a crucial role in regulating gene expression at the post-transcriptional level and have been implicated in the regulation of m6A methylation. Suxiao Jiuxin Pill (SJP) is extensively used in China for the clinical treatment of angina pectoris and confers benefits to patients with acute coronary syndrome who have received percutaneous coronary intervention. However, the precise mechanisms underlying SJP intervention in MIRI remain unclear. PURPOSE: This study aimed to demonstrate, both in vivo and in vitro, that SJP could alleviate autophagy in MIRI by regulating miR-193a-3p to target and upregulate the demethylase ALKBH5. METHODS: An in vitro hypoxia/reoxygenation model was established using H9c2 cells, while an in vivo MIRI model was established using Wistar rats. A lentivirus harboring the precursor sequence of miR-193a-3p was employed for its overexpression. Adeno-associated viruses were used to silence both miR-193a-3p and ALKBH5 expressions. Cardiac function, infarct size, and tissue structure in rats were assessed using echocardiography, triphenyl tetrazolium chloride (TTC) staining, and HE staining, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) was employed to detect the levels of apoptosis in rat cardiac tissue. m6A methylation levels were assessed using colorimetry. GFP-RFP-LC3B was used to monitor autophagic flux and transmission electron microscopy was used to evaluate the development of autophagosomes. Western Blot and qRT-PCR were respectively employed to assess the levels of autophagy-related proteins and miR-193a-3p. RESULTS: SJP alleviated autophagy, preserved cardiac function, and minimized myocardial damage in the hearts of MIRI rats. SJP attenuated autophagy in H/R H9C2 cells. Elevated levels of miR-193a-3p were observed in the cardiac tissues of MIRI rats and H/R H9C2 cells, whereas SJP downregulated miR-193a-3p levels in these models. ALKBH5, a target gene of miR-193, is negatively regulated by miR-193a-3p. Upon overexpression of miR-193a-3p or silencing of ALKBH5, m6A methylation decreased, and the autophagy-attenuating effects of SJP and its components, senkyunolide A and l-borneol, were lost in H/R H9C2 cells, whereas in MIRI rats, these effects were not abolished but merely weakened. Further investigation indicated that the METTL3 inhibitor STM2475, combined with the silencing of miR-193a-3p, similarly attenuated autophagy in the hearts of MIRI rats. This suggests that a reduction in m6A methylation is involved in autophagy alleviation. CONCLUSION: We demonstrated that SJP mitigates autophagy in MIRI by downregulating miR-193a-3p, enhancing ALKBH5 expression, and reducing m6A methylation, a mechanism potentially attributed to its constituents, senkyunolide A and l-borneol.

Borneol-Modified Schisandrin B Micelles Cross the Blood-Brain Barrier To Treat Alzheimer's Disease in Aged Mice.

Objective: Schisandrin B (Sch B) is a bioactive dibenzocyclooctadiene derizative that is prevalent in the fruit of Schisandra chinensis. Numerous studies have demonstrated that Sch B has a neuroprotective action by reducing oxidative stress and effectively preventing inflammation. It follows that Sch B is a potential treatment for Alzheimer's disease (AD). However, the drug's solubility, bioavailability, and lower permeability of the blood-brain barrier (BBB) can all reduce its efficacy during the therapy process. Therefore, this study constructed borneol-modified schisandrin B micelles (Bor-Sch B-Ms), which increase brain targeting by accurately delivering medications to the brain, effectively improving bioavailability. High therapeutic efficacy has been achieved at the pathological site. Methods: Bor-Sch B-Ms were prepared using the thin film dispersion approach in this article. On the one hand, to observe the targeting effect of borneol, we constructed a blood-brain barrier (BBB) model in vitro and studied the ability of micelles to cross the BBB. On the other hand, the distribution of micelle drugs and their related pharmacological effects on neuroinflammation, oxidative stress, and neuronal damage were studied through in vivo administration in mice. Results: In vitro studies have demonstrated that the drug uptake of bEnd.3 cells was increased by the borneol alteration on the surface of the nano micelles, implying that Bor-Sch B-Ms can promote the therapeutic effect of N2a cells. This could result in more medicines entering the BBB. In addition, in vivo studies revealed that the distribution and circulation time of medications in the brain tissue were significantly higher than those in other groups, making it more suitable for the treatment of central nervous system diseases. Conclusion: As a novel nanodrug delivery system, borneol modified schisandrin B micelles have promising research prospects in the treatment of Alzheimer's disease.

Borneol-modified docetaxel plus tetrandrine micelles for treatment of drug-resistant brain glioma.

OBJECTIVE: Glioma is the most common and deadly primary malignant tumor in adults. Treatment outcomes are ungratified due to the presence of blood-brain barrier (BBB), glioma stem cells (GSCs) and multidrug resistance (MDR). Docetaxel (DTX) is considered as a potential drug for the treatment of brain tumor, but its effectiveness is limited by its low bioavailability and drug resistance. Tetrandrine (TET) reverses the resistance of tumor cells to chemotherapy drugs. Borneol (BO) modified in micelles has been shown to promote DTX plus TET to cross the BBB, allowing the drug to better act on tumors. Therefore, we constructed BO-modified DTX plus TET micelles to inhibit chemotherapeutic drug resistance. SIGNIFICANCE: Provide a new treatment method for drug-resistant brain gliomas. METHODS: In this study, BO-modified DTX plus TET micelles were prepared by thin film dispersion method, their physicochemical properties were characterized. Its targeting ability was investigated. The therapeutic effect on GSCs was investigated by in vivo and in vitro experiments. RESULTS: The BO-modified DTX plus TET micelles were successfully constructed by thin film dispersion method, and the micelles showed good stability. The results showed that targeting micelles increased bEnd.3 uptake and helped drugs cross the BBB in vitro. And we also found that targeting micelles could inhibit cell proliferation, promote cell apoptosis and inhibit the expression of drug-resistant protein, thus provide a new treatment method for GSCs in vitro and in vivo. CONCLUSIONS: BO-modified DTX plus TET micelles may provide a new treatment method for drug-resistant brain gliomas.

Borneol promotes autophagic degradation of HIF-1α and enhances chemotherapy sensitivity in malignant glioma.

Background: Gliomas are characterized by high mortality rates and resistance. Even with conventional chemotherapy the prognosis of glioblastoma remains poor. Many medications are not optimally effective due to limited bioavailability. The bioavailability of medicine can be enhanced by borneol, a monoterpenoid substance. In this study, we investigated the effect of borneol, a commonly used Chinese medicine, on chemosensitivity in C6 glioma and U251 human glioma cell lines and elucidated its therapeutic molecular targets. Methods: The chemosensitivity-inducing effects of borneol in C6 and U251 cells were examined using CCK8 and clonal formation assays. The mechanism underlying the effect of borneol was evaluated through immunohistochemistry and western blotting assays. Further, the number of autophagosomes was determined via transmission electron microscopy. Finally, the chemical sensitization effect of borneol was evaluated in SD rats after C6 orthotopic tumor transplantation. Results: Borneol increased cytotoxicity in C6 and U251 cells in response to temozolomide (TMZ). In addition, through transmission electron microscopy, western blotting, and immunohistochemical tests, we found that borneol combined with TMZ significantly increased the level of autophagy and that hypoxia inducible factor-1(HIF-1α) is a candidate target through which borneol enhances the cytotoxic effect of TMZ. Borneol's ability to enhance HIF-1α degradation was counteracted following the administration of autophagy inhibitors. In vivo, borneol treatment was found to enhance the anticancer effect of TMZ and delay tumor progression, and this effect was closely related to its ability to promote the autophagic degradation of HIF-1α. Conclusions: HIF-1α might be a valid therapeutic target of borneol, which can be potentially applied as a chemosensitizing drug used for glioma treatment.

Molecularly Imprinted Heterostructure-Based Electrochemosensor for Ultratrace and Precise Detection of 2-Methylisoborneol in Water.

Ultratrace 2-methylisoborneol (2-MIB, ∼ng/L) in source water is the main odorant in the algae-derived odor episodes, whose accurate on-site detection will have a promising application potential. Due to the chemical inertness of 2-MIB, sensitive and selective detection of 2-MIB remains much challenging. Herein, molecularly imprinted polymer cavities were polymerized on the heterostructure Ti3C2Tx@CuFc-metal-organic framework to selectively capture 2-MIB, where the heterostructure could catalyze the probe redox reaction of [Fe(CN)63-/4-] and amplify the corresponding current signals. The prepared electrochemical sensor showed higher sensitivity on 2-MIB detection than the reported ones. Excellent stability, reusability, and selectivity for 2-MIB detection were also verified. The linear range and limit of detection of our sensor for 2-MIB were optimized to 0.0001-100 µg/L and 30 pg/L, respectively, performing much better than the reported sensors. Comparable performance to gas chromatography-mass spectrometry was achieved when the sensor was applied to real water samples with or without 2-MIB standards. Overall, our research has made great progress in the application of an on-site sensor in 2-MIB detection and well advances the development of molecularly imprinted polymer-based electrochemical sensors.

Dual fluorescence images, transport pathway, and blood-brain barrier penetration of B-Met-W/O/W SE.

Borneol is an aromatic traditional Chinese medicine that can improve the permeability of the blood-brain barrier (BBB), enter the brain, and promote the brain tissue distribution of many other drugs. In our previous study, borneol-metformin hydrochloride water/oil/water composite submicron emulsion (B-Met-W/O/W SE) was prepared using borneol and SE to promote BBB penetration, which significantly increased the brain distribution of Met. However, the dynamic images, transport pathway (uptake and efflux), promotion of BBB permeability, and mechanisms of B-Met-W/O/W SE before and after entering cells have not been clarified. In this study, rhodamine B and coumarin-6 were selected as water-soluble and oil-soluble fluorescent probes to prepare B-Met-W/O/W dual-fluorescent SE (B-Met-W/O/W DFSE) with concentric circle imaging. B-Met-W/O/W SE can be well taken up by brain microvascular endothelial cells (BMECs). The addition of three inhibitors (chlorpromazine hydrochloride, methyl-ß-cyclodextrin, and amiloride hydrochloride) indicated that its main pathway may be clathrin-mediated and fossa protein-mediated endocytosis. Meanwhile, B-Met-W/O/W SE was obviously shown to inhibit the efflux of BMECs. Next, BMECs were cultured in the Transwell chamber to establish a BBB model, and Western blot was employed to detect the protein expressions of Occludin, Zona Occludens 1 (ZO-1), and p-glycoprotein (P-gp) after B-Met-W/O/W SE treatment. The results showed that B-Met-W/O/W SE significantly down-regulated the expression of Occludin, ZO-1, and P-gp, which increased the permeability of BBB, promoted drug entry into the brain through BBB, and inhibited BBB efflux. Furthermore, 11 differentially expressed genes (DEGs) and 7 related signaling pathways in BMECs treated with B-W/O/W SE were detected by transcriptome sequencing and verified by quantitative real-time polymerase chain reaction (qRT-PCR). These results provide a scientific experimental basis for the dynamic monitoring, transmembrane transport mode, and permeation-promoting mechanism of B-Met-W/O/W SE as a new brain-targeting drug delivery system.

Role of acrylates in the development of contact dermatitis in diabetic patients-A Polish dermatology tertiary centre experience.

BACKGROUND: In recent years, an increasing number of contact dermatitis cases triggered by acrylates contained in diabetes medical devices have been reported. Acrylates seem to play a major role in the development of irritant contact dermatitis and allergic contact dermatitis (ACD) in diabetic patients. OBJECTIVES: To study a group of patients with contact dermatitis caused by diabetes medical devices with a focus on acrylates as possible allergens responsible for contact dermatitis. PATIENTS AND METHODS: Fifteen patients with diabetes mellitus type 1 and contact dermatitis from diabetic devices were patch tested to 25 acrylate allergens. RESULTS: Three patients (20%) reacted to the following allergens: three patients reacted to isobornyl acrylate (IBOA) and one of them additionally to 2-hydroxyethyl acrylate (2-HEA); results were of clinical relevance. All three patients were using insulin pumps and glucose sensors (GS)-in one patient contact dermatitis was towards the insulin pump and the GS, in one patient only towards the insulin pump and in one patient only towards the GS. Twelve patients (80%) did not show any skin reaction towards the allergens tested. CONCLUSION: A majority of diabetic patients showed no reactions towards any acrylate allergen tested; yet, the presence of untested allergens must be kept in mind. IBOA proved to be a cause of ACD in diabetes patients. 2-HEA might be another culprit allergen, but its presence in the devices must first be confirmed.

Combination of fenchone and sodium hyaluronate ameliorated constipation-predominant irritable bowel syndrome and underlying mechanisms.

We sought to explore the protective effect of the combination of fenchone (FE) and sodium hyaluronate (SH) on ice water-induced IBS-C rats and the potential mechanism. The neurotransmitter levels, including substance P (SP), motilin (MTL), 5-hydroxytryptamine (5-HT), and vasoactive intestinal peptide (VIP), were determined by ELISA methods. The stem cell factors (SCF)/c-Kit signaling pathway-related protein and mRNA levels were determined by western blot and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses, respectively. The expressions of tight ZO-1, Occludin, and Claudin-1 were also measured by western blot assay and immunofluorescence staining. The 16S rRNA gene sequence was used to measure the composition of gut microbiota. The co-administration of FE and SH improved the body weight, number of fecal pellets, fecal moisture, abdominal with drawal reflex score, and gastrointestinal transit rate in IBS-C rats. The unique efficacy of combination depended on the regulation of balance between excitatory and inhibitory neurotransmitters, enhancement of intestinal barrier function, and activation of SCF/c-Kit pathway. The gut microbiota structure was also restored. The ability of FE combined with SH to regulate SCF/c-Kit signaling pathway, enhance intestinal barrier function, and modulate gut microbiota contributes to their efficacy in managing IBS-C in rats.

New Facts on the Antimicrobial Essential Oil of Satureja kitaibelii.

The objective of the present study was to assess the difference in antimicrobial activity of Satureja kitaibelii Wierzb. ex Heuff. essential oil at three growth stages. In addition, using statistical and chemometric tools, we tried to explain why the essential oil from a certain vegetation stage shows the highest antimicrobial activity. S. kitaibelii essential oils demonstrated minimum inhibitory concentration values from 160 to 10000 µg mL-1 , and minimum microbicidal concentration values from 630 to 20000 µg mL-1 . Geraniol, borneol, limonene and p-cymene are the dominant compounds of S. kitaibelii essential oil. The most abundant compound, geraniol, possesses antimicrobial activity in a range of MIC values from 40 to 5000 µg mL-1 and MMC values from 80 to 10000 µg mL-1 . The highest activity of essential oil for all tested strains of microorganisms was recorded in November. Results of statistical analysis indicate that the percentage of dominant compounds of essential oils does not affect the antibacterial activity of essential oils. Chemometric analyses leads to the conclusion that borneol, spathulenol, caryophyllene oxide and limonene can be the main contributors to the antibacterial activity of essential oil from November and that their mutual ratio is important. These results may represent a new methodological approach for future research on essential oils.

Maintenance of cell integrity during hydroxyl radical rapid inactivation of Pseudanabaena sp. and simultaneous mineralization of odor compound 2-methylisoborneol.

Pseudanabaena sp. and the odor compound it produces, 2-methylisoborneol (2-MIB), has been reportedly responsible for off-flavor pollution worldwide, leading to substandard drinking water sensory indicators and serious water supply crises. In this paper, the hydroxyl radical (•OH) produced by the synergistic effect of strong ionization discharge and hydrodynamic cavitation rapidly inactivated Pseudanabaena sp. and simultaneously mineralized 2-MIB to a concentration of 2.57 ng/L, which is below the odor threshold of 10 ng/L for a total reactive oxidants (TRO) concentration of 1.2 mg/L within 12 s. Crucially, the intracellular 2-MIB level was maintained in approximately 155.26- 162.29 ng/L range, indicating that 2-MIB was not released from the cells. Based on the scanning electron microscopy (SEM) results, the integrity of Pseudanabaena sp. cells was maintained with intact membranes and no intracellular organic matters (IOM) released during •OH inactivation. In contrast, ClO2 caused severe membrane rupture and massive IOM release. Based on the gas chromatograph/mass spectrometer (GC/MS) analyses and mass spectral database, the chromatogram fitted the baseline with a TRO concentration of 4 mg/L and no peaks corresponding to intermediates were detected. Moreover, •OH could mineralize 2-MIB by opening the ring structures of 1,2,3,3-tetramethyl-4-cyclopentenone, neomenthol, and 2-methylcyclohexene-1-aldehyde to produce small-molecule compounds, finally leading to CO2 and H2O formation via three reaction pathways. Therefore, the •OH not only maintained the cell integrity of Pseudanabaena sp. during inactivation but also mineralized 2-MIB simultaneously.