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Indian Journal of Pharmacology Jan 2024Cosmeceuticals are topically applied cosmetic products containing a biologically active ingredient with a pharmaceutical effect that improves, nourishes, and treats the... (Review)
Review
Cosmeceuticals are topically applied cosmetic products containing a biologically active ingredient with a pharmaceutical effect that improves, nourishes, and treats the skin appearance. The trend of cosmeceuticals began during the mid-20th century due to its potent ingredients with therapeutic effects for various skin ailments. Even though there is a great advancement in cosmetics, which shows the risk of cosmetic linked melanoma, endocrine disorders, and birth defects which was one in 1500 people during 1935 have increased to one in 75 people in 2000. Hence, as a part of reducing the harmful effect, natural ingredients were added to the formulation to give the pharmaceutical effect. Thus, natural/herbal cosmeceuticals were introduced. Due to the awareness of the side effects such as photo-toxicity, mutagenicity, irritation by these synthetic products, people started preferring herbal/natural cosmetic products. Moreover, natural cosmeceuticals were proven to be effective against various dermatological conditions as well as have fewer side effects marked the natural/herbal cosmeceuticals in the market. Unlike a drug, cosmeceutical products undergo safety, toxicity, and efficacy tests, but these are not classified under Food and Drug Administration. This review will give an insight into different natural ingredients used in natural/herbal cosmeceutical formulation and their function challenges faced during formulation, advantages of natural cosmeceuticals over regular cosmeceuticals, and regulatory aspects in India.
Topics: Humans; Cosmeceuticals; Cosmetics; Skin; Pharmaceutical Preparations; Pharmaceutical Vehicles; Biological Products
PubMed: 38454588
DOI: 10.4103/ijp.ijp_244_21 -
Science Advances Mar 2024Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from...
Synergistic phototherapy stands for superior treatment prospects than a single phototherapeutic modality. However, the combined photosensitizers often suffer from incompatible excitation mode, limited irradiation penetration depth, and lack of specificity. We describe the development of upconversion dual-photosensitizer-expressing bacteria (UDPB) for near-infrared monochromatically excitable combination phototherapy. UDPB are prepared by integrating genetic engineering and surface modification, in which bacteria are encoded to simultaneously express photothermal melanin and phototoxic KillerRed protein and the surface primary amino groups are derived to free thiols for biorthogonal conjugation of upconversion nanoparticles. UDPB exhibit a near-infrared monochromatic irradiation-mediated dual-activation characteristic as the photothermal conversion of melanin can be initiated directly, while the photodynamic effect of KillerRed can be stimulated indirectly by upconverted visible light emission. UDPB also show living features to colonize hypoxic lesion sites and inhibit pathogens via bacterial community competition. In two murine models of solid tumor and skin wound infection, UDPB separately induce robust antitumor response and a rapid wound healing effect.
Topics: Animals; Mice; Photosensitizing Agents; Melanins; Phototherapy; Bacteria; Infrared Rays
PubMed: 38446879
DOI: 10.1126/sciadv.adk9485 -
Research (Washington, D.C.) 2023Visualizing cellular structures especially the cytoskeleton and the nucleus is crucial for understanding mechanobiology, but traditional fluorescence staining has...
Visualizing cellular structures especially the cytoskeleton and the nucleus is crucial for understanding mechanobiology, but traditional fluorescence staining has inherent limitations such as phototoxicity and photobleaching. Virtual staining techniques provide an alternative approach to addressing these issues but often require substantial amount of user training data. In this study, we develop a generalizable cell virtual staining toolbox (termed CellVisioner) based on few-shot transfer learning that requires substantially reduced user training data. CellVisioner can virtually stain F-actin and nuclei for various types of cells and extract single-cell parameters relevant to mechanobiology research. Taking the label-free single-cell images as input, CellVisioner can predict cell mechanobiological status (e.g., Yes-associated protein nuclear/cytoplasmic ratio) and perform long-term monitoring for living cells. We envision that CellVisioner would be a powerful tool to facilitate on-site mechanobiological research.
PubMed: 38434246
DOI: 10.34133/research.0285 -
JACS Au Feb 2024A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising...
A small chemical modification of the nucleobase structure can significantly enhance the photoactivity of DNA, which may incur DNA damage, thus holding promising applications in photochemotherapy treatment of cancers or pathogens. However, single substitution confers only limited phototoxicity to DNA. Herein, we combine femtosecond and nanosecond time-resolved spectroscopy with high-level calculations to disentangle the excited-state dynamics of 6-methylthioguanine (me6-TG) under variable wavelength UVA excitation (310-330 nm). We find that double substitution of nucleobases (thionation and methylation) boosts the photoactivity by introducing more reactive channels. Intriguingly, nπ*, rather than nπ*, acts as the doorway state engendering the formation of the long-lived reactive triplet state in me6-TG. The nπ* induces a low spin-orbit coupling of 8.3 cm, which increases the intersystem crossing (ISC) time (2.91 ± 0.14 ns). Despite the slowed ISC, the triplet quantum yield (Φ) still accounts for a large fraction (0.6 ± 0.1), consistent with the potential energy surface that favors excited-state bifurcation to nπ* (3.36 ± 0.15 ps) rather than ππ* (5.05 ± 0.26 ps), such that the subsequent ISC to triplet via nπ* constitutes the main relaxation pathway in me6-TG. Although this Φ is inferior to its single-substituted predecessor 6-thioguanine (6-TG, 0.8 ± 0.2), the effect of thionation in synergy with methylation opens a unique C-S bond cleavage pathway through crossing to a repulsive πσ* state, generating thiyl radicals as highly reactive intermediates that may invoke biological damage. This photodissociation channel is extremely difficult for conventional nucleobases. These findings demonstrate the synergistic effects of double functionality substitution in modulating excited-state dynamics and enhancing the photolabile character of DNA nucleobases, providing inspirations for the rational design of advanced photodynamic and photochemotherapy approaches.
PubMed: 38425924
DOI: 10.1021/jacsau.3c00575 -
Planta Medica May 2024Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell... (Review)
Review
Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.
Topics: Photosensitizing Agents; Biological Products; Photochemotherapy; Reactive Oxygen Species; Curcumin; Neoplasms
PubMed: 38423033
DOI: 10.1055/a-2257-9194 -
Investigative Ophthalmology & Visual... Feb 2024RPE disruption with light exposures below or close to the American National Standards Institute (ANSI) photochemical maximum permissible exposure (MPE) have been...
PURPOSE
RPE disruption with light exposures below or close to the American National Standards Institute (ANSI) photochemical maximum permissible exposure (MPE) have been observed, but these findings were limited to two wavelengths. We have extended the measurements across the visible spectrum.
METHODS
Retinal imaging with fluorescence adaptive optics scanning light ophthalmoscopy (FAOSLO) was used to provide an in vivo measure of RPE disruption at a cellular level. The threshold retinal radiant exposures (RREs) for RPE disruption (localized detectable change in the fluorescence image) were determined at 460, 476, 488, 530, 543, 561, 594, 632, and 671 nm (uniform 0.5° square exposure) using multiples locations in 4 macaques.
RESULTS
FAOSLO is sensitive in detecting RPE disruption. The visible light action spectrum dependence for RPE disruption with continuous wave (CW) extended field exposures was determined. It has a shallower slope than the current ANSI blue-light hazard MPE. At all wavelengths beyond 530 nm, the disruption threshold is below the ANSI blue-light hazard MPE. There is reciprocity of exposure irradiance and duration for exposures at 460 and 594 nm.
CONCLUSIONS
We measured with FAOSLO the action spectrum dependence for photochemical RPE disruption across the visible light spectrum. Using this in vivo measure of phototoxicity provided by FAOSLO, we find that thresholds are lower than previously measured. The wavelength dependence in our data is considerably shallower than the spectral dependence of the traditional ANSI blue-light hazard, emphasizing the need for more caution with increasing wavelength than expected.
Topics: Animals; Retinal Pigment Epithelium; Retina; Blue Light; Fluorescence; Macaca; Primates
PubMed: 38416456
DOI: 10.1167/iovs.65.2.43 -
Journal of Photochemistry and... Feb 2024Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic...
Photosensitivity to structurally diverse drugs is a common but under-reported adverse cutaneous reaction and can be classified as phototoxic or photoallergic. Phototoxic reactions occur when the skin is exposed to sunlight after administering topical or systemic medications that exhibit photosensitizing activity. These reactions depend on the dose of medication, degree of exposure to ultraviolet light, type of ultraviolet light, and sufficient skin distribution volume. Accurate prediction of the incidence and phototoxic response severity is challenging due to a paucity of literature, suggesting that phototoxicity may be more frequent than reported. This paper reports an extensive literature review on phototoxic drugs; the review employed pre-determined search criteria that included meta-analyses, systematic reviews, literature reviews, and case reports freely available in full text. Additional reports were identified from reference sections that contributed to the understanding of phototoxicity. The following drugs and/or drug classes are discussed: amiodarone, voriconazole, chlorpromazine, doxycycline, fluoroquinolones, hydrochlorothiazide, nonsteroidal anti-inflammatory drugs, and vemurafenib. In reviewing phototoxic skin reactions, this review highlights drug molecular structures, their reactive pathways, and, as there is a growing association between photosensitizing drugs and the increasing incidence of skin cancer, the consequential long-term implications of photocarcinogenesis.
PubMed: 38389933
DOI: 10.1016/j.jpap.2023.100221 -
Inorganic Chemistry Apr 2024Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to...
Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to obtain photolabile Ru(II) complexes. The two most explored have been the use of monodentate ligands and the incorporation of steric effects between the bidentate ligands and the Ru(II). However, the introduction of electronic effects in the ligands has been less explored. Herein, we report a systematic experimental, theoretical, and photocytotoxicity study of a novel series of Ru(II) complexes - of general formula [Ru(phen)(NN')], where NN' are different minimal strained ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH (), F (), CF (), NO (), and N(CH) () substituents in the R4 of the phenyl ring. The complexes are stable in solution in the dark, but upon irradiation in water with blue light (λ = 465 nm, 4 mW/cm) photoejection of the ligand BTAT was observed by HPLC-MS spectrometry and UV-vis spectroscopy, with ranging from 4.5 to 14.15 min depending of the electronic properties of the corresponding BTAT, being the less photolabile (the one containing the more electron withdrawing substituent, NO). The properties of the ground state singlet and excited state triplet of have been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. A mechanism for the photoejection of the BTAT ligand from the Ru complexes, in HO, is proposed. Phototoxicity studies in A375 and HeLa human cancer cell lines showed that the new Ru BTAT complexes were strongly phototoxic. An enhancement of the emission intensity of HeLa cells treated with was observed in response to increasing doses of light due to the photoejection of the BTAT ligand. These studies suggest that BTAT could serve as a photocleavable protecting group for the cytotoxic bis-aqua ruthenium warhead [Ru(phen)(OH)].
Topics: Humans; Chelating Agents; Ruthenium; Ligands; HeLa Cells; Nitrogen Dioxide; Neoplasms
PubMed: 38385171
DOI: 10.1021/acs.inorgchem.3c04432 -
Frontiers in Neurology 2024This Mendelian randomization (MR) study identified modifiable risk factors for isolated rapid eye movement sleep behavior disorder (iRBD).
OBJECTIVES
This Mendelian randomization (MR) study identified modifiable risk factors for isolated rapid eye movement sleep behavior disorder (iRBD).
METHODS
Genome-wide association study (GWAS) datasets for 29 modifiable risk factors for iRBD in discovery and replication stages were used. GWAS data for iRBD cases were obtained from the International RBD Study Group. The inverse variance weighted (IVW) method was primarily employed to explore causality, with supplementary analyses used to verify the robustness of IVW findings. Co-localization analysis further substantiated causal associations identified via MR. Genetic correlations between mental illness and iRBD were identified using trait covariance, linkage disequilibrium score regression, and co-localization analyses.
RESULTS
Our study revealed causal associations between sun exposure-related factors and iRBD. Utilizing sun protection (odds ratio [OR] = 0.31 [0.14, 0.69], = 0.004), ease of sunburn (OR = 0.70 [0.57, 0.87], = 0.001), childhood sunburn occasions (OR = 0.58 [0.39, 0.87], = 0.008), and phototoxic dermatitis (OR = 0.78 [0.66, 0.92], = 0.003) decreased iRBD risk. Conversely, a deep skin color increased risk (OR = 1.42 [1.04, 1.93], = 0.026). Smoking, alcohol consumption, low education levels, and mental illness were not risk factors for iRBD. Anxiety disorders and iRBD were genetically correlated.
CONCLUSION
Our study does not corroborate previous findings that identified smoking, alcohol use, low education, and mental illness as risk factors for iRBD. Moreover, we found that excessive sun exposure elevates iRBD risk. These findings offer new insights for screening high-risk populations and devising preventive measures.
PubMed: 38385030
DOI: 10.3389/fneur.2024.1321216 -
Patient Related Outcome Measures 2024Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on...
Development and Content Validation of Novel Patient-Reported Outcome Measures to Assess Disease Severity and Change in Patients with Erythropoietic Protoporphyria: The EPP Impact Questionnaire (EPIQ).
PURPOSE
Erythropoietic protoporphyria (EPP), a rare inherited disorder, presents in early childhood with severe, painful phototoxicity, with significant impacts on health-related quality of life (HRQoL). Previous studies have not captured all concepts important to patients. Therefore, this study sought to develop a novel, comprehensive, and content valid patient-reported outcome (PRO) measure to assess the efficacy of new therapies.
PATIENTS AND METHODS
Qualitative interviews were conducted with EPP participants and clinical experts to obtain views on concepts relevant to patients. Results informed the development of novel PROs, which were debriefed during subsequent combined concept elicitation and cognitive debriefing interviews.
RESULTS
Twenty-three interviews were conducted with 17 adults and 6 adolescents with EPP. Concept elicitation revealed that participants experienced many symptoms with significant variability. The most common were burning, pain, swelling, and tingling. Tingling was the most common prodromal symptom, while burning was the most bothersome, and pain was the worst full reaction symptom. Participants reported being negatively impacted in their ability to do daily activities, and social and emotional functioning. Many reported impacted ability to work and be productive at their job. Participants reviewed and completed the newly developed PRO measures assessing full reactions and ability to do activities, as well as items to assess severity and change in severity of prodromal symptoms, full reactions, and EPP overall. All measures were found to be comprehensive, clear, and relevant.
CONCLUSION
PRO measures are needed to assess important aspects of HRQoL and evaluate therapeutic response. These PRO measures are unique in assessing overall severity and change in EPP.
PubMed: 38375415
DOI: 10.2147/PROM.S438892