Mobilization of specific mechanisms of regulated cell death is a promising alternative to treat challenging illness such as neurodegenerative disease and cancer. The use of light to activate these ...mechanisms may provide a route for target-specific therapies. Two asymmetric porphyrins with opposite charges, the negatively charged TPPS
and the positively charged CisDiMPyP were compared in terms of their properties in membrane mimics and in cells. CisDiMPyP interacts to a larger extent with model membranes and with cells than TPPS
, due to a favorable electrostatic interaction. CisDiMPyP is also more effective than TPPS
in damaging membranes. Surprisingly, TPPS
is more efficient in causing photoinduced cell death. The lethal concentration on cell viability of 50% (LC
) found for TPPS
was ~3.5 (raw data) and ~5 (considering photosensitizer incorporation) times smaller than for CisDiMPyP. CisDiMPyP damaged mainly mitochondria and triggered short-term phototoxicity by necro-apoptotic cell death. Photoexcitation of TPPS
promotes mainly lysosomal damage leading to autophagy-associated cell death. Our data shows that an exact damage in lysosome is more effective to diminish proliferation of HeLa cells than a similar damage in mitochondria. Precisely targeting organelles and specifically triggering regulated cell death mechanisms shall help in the development of new organelle-target therapies.
Protecting human skin from sun exposure is a complex issue that involves unclear aspects of the interaction between light and tissue. A persistent misconception is that visible light is safe for the ...skin, although several lines of evidence suggest otherwise. Here, we show that visible light can damage melanocytes through melanin photosensitization and singlet oxygen (1O2) generation, thus decreasing cell viability, increasing membrane permeability, and causing both DNA photo-oxidation and necro-apoptotic cell death. UVA (355 nm) and visible (532 nm) light photosensitize 1O2 with similar yields, and pheomelanin is more efficient than eumelanin at generating 1O2 and resisting photobleaching. Although melanin can protect against the cellular damage induced by UVB, exposure to visible light leads to pre-mutagenic DNA lesions (i.e., Fpg- and Endo III-sensitive modifications); these DNA lesions may be mutagenic and may cause photoaging, as well as other health problems, such as skin cancer.
Photobiomodulation: Cellular, molecular, and clinical aspects Felician, Márcia Cristina Prado; Belotto, Renata; Tardivo, João Paulo ...
Journal of photochemistry and photobiology,
October 2023, 2023-10-00, 2023-10-01, Volume:
17
Journal Article
Peer reviewed
Open access
Photobiomodulation (PBM) is a noninvasive photonic-based therapy, capable of dealing with immune-inflammatory, neurological, and musculoskeletal disorders, as well as healing oral and chronic skin ...wounds. During PBM light is applied at a specific wavelength, either in the visible or near-infrared (NIR) ranges. Photophysical and photochemical processes might stimulate or inhibit various biological processes, depending on the target tissue, the wavelength of light, irradiance, fluence, repetition rate (pulse frequency), spot size, optical data of the tissue to be irradiated and treatment regimen. There are several randomized clinical studies demonstrating the PBM benefits as main or adjuvant therapies. Of importance to this review, there is a large piece of evidence in the management of skin or venous ulcers, and diabetic foot. In this review, the PBM´s efficacy as adjuvant therapy to deal with chronic human ulcers were discussed concerning the photophysical parameters and clinical aspects. Beside, we overview the state-of-the-art regarding the cellular and molecular modulatory mechanisms photoactivated by red and NIR light.
The premature aging (photoaging) of skin characterized by wrinkles, a leathery texture and mottled pigmentation is a well-documented consequence of exposure to sunlight. UVA is an important risk ...factor for human cancer also associated with induction of inflammation, immunosuppression, photoaging and melanogenesis. Although herbal compounds are commonly used as photoprotectants against the harmful effects of UVA, the mechanisms involved in the photodamage are not precisely known. In this study, we investigated the effects of Aloe Vera (Aloe barbadensis mil) on the protection against UVA-modulated cell killing of HaCaT keratinocytes. Aloe Vera exhibited the remarkable ability of reducing both in vitro and in vivo photodamage, even though it does not have anti-radical properties. Interestingly, the protection conferred by Aloe Vera was associated with the maintenance of membrane integrity in both mimetic membranes and intracellular organelles. The increased lysosomal stability led to a decrease in lipofuscinogenesis and cell death. This study explains why Aloe Vera extracts offer protection against photodamage at a cellular level in both the UV and visible spectra, leading to its beneficial use as a supplement in protective dermatological formulations.
Zika virus (ZIKV) is an arbovirus mainly transmitted by mosquitos of the genus
Aedes
. The first cases of ZIKV infection in South America occurred in Brazil in 2015. The infection in humans causes ...diverse symptoms from asymptomatic to a syndrome-like dengue infection with fever, arthralgia, and myalgia. Furthermore, ZIKV infection during pregnancy is associated with fetal microcephaly and neurological disorders. The identification of host molecular mechanisms responsible for the modulation of different signaling pathways in response to ZIKV is the first step to finding potential biomarkers and therapeutic targets and understanding disease outcomes. In the last decade, it has been shown that microRNAs (miRNAs) are important post-transcriptional regulators involved in virtually all cellular processes. miRNAs present in body fluids can not only serve as key biomarkers for diagnostics and prognosis of human disorders but also contribute to cellular signaling offering new insights into pathological mechanisms. Here, we describe for the first time ZIKV-induced changes in miRNA plasma levels in patients during the acute and recovery phases of infection. We observed that during ZIKV acute infection, among the dysregulated miRNAs (DMs), the majority is with decreased levels when compared to convalescent and control patients. We used systems biology tools to build and highlight biological interactions between miRNAs and their multiple direct and indirect target molecules. Among the 24 DMs identified in ZIKV + patients, miR-146, miR-125a-5p, miR-30-5p, and miR-142-3p were related to signaling pathways modulated during infection and immune response. The results presented here are an effort to open new vistas for the key roles of miRNAs during ZIKV infection.
Atherosclerosis is a complex disease in which vessels develop plaques comprising dysfunctional endothelium, monocyte derived lipid laden foam cells and activated lymphocytes. Considering that humans ...and animal models of the disease develop quite distinct plaques, we used human plaques to search for proteins that could be used as markers of human atheromas. Phage display peptide libraries were probed to fresh human carotid plaques, and a bound phage homologous to plexin B1, a high affinity receptor for CD100, was identified. CD100 is a member of the semaphorin family expressed by most hematopoietic cells and particularly by activated T cells. CD100 expression was analyzed in human plaques and normal samples. CD100 mRNA and protein were analyzed in cultured monocytes, macrophages and foam cells. The effects of CD100 in oxLDL-induced foam cell formation and in CD36 mRNA abundance were evaluated. Human atherosclerotic plaques showed strong labeling of CD100/SEMA4D. CD100 expression was further demonstrated in peripheral blood monocytes and in in vitro differentiated macrophages and foam cells, with diminished CD100 transcript along the differentiation of these cells. Incubation of macrophages with CD100 led to a reduction in oxLDL-induced foam cell formation probably through a decrease of CD36 expression, suggesting for the first time an atheroprotective role for CD100 in the human disease. Given its differential expression in the numerous foam cells and macrophages of the plaques and its capacity to decrease oxLDL engulfment by macrophages we propose that CD100 may have a role in atherosclerotic plaque development, and may possibly be employed in targeted treatments of these atheromas.
Autophagy is a critical metabolic process that supports homeostasis at a basal level and is dynamically regulated in response to various physiological and pathological processes. Autophagy has some ...etiologic implications that support certain pathological processes due to alterations in the lysosomal-degradative pathway. Some of the conditions related to autophagy play key roles in highly relevant human diseases, e.g., cardiovascular diseases (15.5%), malignant and other neoplasms (9.4%), and neurodegenerative conditions (3.7%). Despite advances in the discovery of new strategies to treat these age-related diseases, autophagy has emerged as a therapeutic option after preclinical and clinical studies. Here, we discuss the pitfalls and success in regulating autophagy initiation and its lysosome-dependent pathway to restore its homeostatic role and mediate therapeutic effects for cancer, neurodegenerative, and cardiac diseases. The main challenge for the development of autophagy regulators for clinical application is the lack of specificity of the repurposed drugs, due to the low pharmacological uniqueness of their target, including those that target the PI3K/AKT/mTOR and AMPK pathway. Then, future efforts must be conducted to deal with this scenery, including the disclosure of key components in the autophagy machinery that may intervene in its therapeutic regulation. Among all efforts, those focusing on the development of novel allosteric inhibitors against autophagy inducers, as well as those targeting autolysosomal function, and their integration into therapeutic regimens should remain a priority for the field.
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•Autophagy highlights a promising therapeutic/preventive avenue to deal with neurodegenerative, cardiac, or cancer diseases.•Autophagy modulation may implicate in off-target effects if the specificity of the current drugs would not be addressed.•As a future perspective, the impact of inducing mitophagy parallel to lysosomal dysfunction has been highlighted.
Visible light can induce the generation of singlet oxygen and can cause oxidative stress, especially in melanocytes due to melanin photosensitization. Currently, there is no organic UV-filter that ...provide visible light protection. Previous studies showed that some antioxidants, such as apigenin (API), chrysin (CRI) and beta-carotene (BTC) besides neutralizing radical chain reactions can also quench singlet oxygen via physical or chemical quenching and exhibit potential for use in photoprotection. Therefore, the aim of this study is to evaluate the efficacy of API, CRI and BTC on the protection against cell death induced by melanin photosensitization and understand the underlying mechanisms that are involved in the protection. Precise protocols of melanogenesis and quantification of singlet oxygen generation were developed. Viability of B16-F10 cells with melanin basal levels and after melanogenesis induction was evaluated after visible light exposure in the presence and absence of API, CRI and BTC. Results showed that API and BTC protected cells from photoinduced cell death API exhibiting superior photoprotective effect. We noticed that the efficiency of cell protection and the rate of singlet oxygen suppression are not well correlated, at least for the studied series of antioxidants, indicating that the anti-radical capacity should be playing a major role in protecting cells against the damage induced by melanin photosensitization. In terms of sun care strategies, both API and BTC offer protection against visible light-induced damages and may be effective topical antioxidants to be added to sunscreens.
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•API and BTC protected melanocytes from photoinduced cell death.•API exhibited superior photoprotective effect.•API and BTC play an important role on in vitro protection against photodamage.•API and BTC may be effective topical antioxidants to be added to sunscreens.
In order to understand the intracellular delivery of drugs and to improve the cell killing efficiency of photosensitizers (PSs) used in photodynamic therapy (PDT), we prepared TyroSphere ...nanoparticles, which are triblock polymer poly(ethylene glycol)-block-oligo(desaminotyrosyltyrosine octyl ester suberate)-block-poly(ethylene glycol) aggregates, loaded with amphiphilic porphyrins with either positive (CisDiMPyP) or negative (TPPS2a) charges. Their physicochemical and photochemical properties were investigated, as well as the efficiency and mechanism of PDT death in a cervical cancer cell line (HeLa). The photophysical properties of both PSs were improved when loaded in the nanocarrier, with a decrease in aggregation as well as an increase in the yield of singlet oxygen generation. The physical and chemical stability of TyroSphere nanoparticles allows them to enter cells and to promote the slow intracellular delivery of part of the PSs. Confocal steady-state and lifetime-resolved fluorescence imaging microscopy data showed that the released PSs are free to target their natural intracellular targets, which are mitochondria and lysosomes for CisDiMPyP and TPPS2a, respectively. The photodynamic efficiency of cell killing was increased considerably compared with the free PSs (∼3×), but the mechanism of cell death was the same as that of the free PSs, which are acute necro-apoptosis for CisDiMPyP and autophagy malfunction for TPPS2a, reflecting the specific damage in mitochondria and lysosomes, respectively. We are confident that TyroSpheres provide a novel and efficient platform to administrate PDT photosensitizers, as well as other drugs with intracellular targets.
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