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By Vijay Kumar Malesu Feb 14 2024 Reviewed by Lily Ramsey, LLM

In a recent study published in Scientific Reports, a group of researchers evaluated how melanin content and distribution affect ultraviolet (UV)-induced deoxyribonucleic acid (DNA) damage in skin, using reconstructed human epidermis (RHE) models.

Study:  Significance of melanin distribution in the epidermis for the protective effect against UV light . Image Credit: rangizzz/Shutterstock.com Background 

While ultraviolet radiation (UVR) is crucial for vitamin D and endorphins, its overexposure increases the risk of skin cancer through DNA damage.

This damage occurs via UV-B absorption and UV-A-induced radicals, leading to specific DNA lesions. Thanks to melanin, skin pigmentation offers substantial photoprotection, notably reducing cancer rates in darker skin.

Melanin's effectiveness is attributed to its UV-blocking, antioxidant, and radical-neutralizing properties. Nonetheless, the role of melanin is complex, as it may also enhance cell sensitivity to UVR damage.

This contradiction prompts a need for further research to understand melanin's dual effects on photoprotection and photosensitization in skin cancer dynamics. About the study 

In the present study, RHE models developed from primary epidermal keratinocytes and melanocytes of Asian-Caucasian and Afro-American donors were categorized into tanned and light based on their melanin content, established through a newly validated method on ex vivo human skin.

This method involved melanin extraction and spectrometric analysis at 500 nm wavelength, correlating melanin levels with the Individual Typological Angle (ITA°), a measure of skin pigmentation.

Ex vivo human skin samples, sourced from healthy individuals of various ethnic backgrounds undergoing surgery, were used to calibrate the melanin quantification process. These samples allowed researchers to classify the RHE models according to melanin content, facilitating a comparison between light and tanned models. Related StoriesGenetics of estrogen production linked to endometrial cancer risk in postmenopausal womenPlant-based diet linked to less erectile dysfunction, urinary incontinence in prostate cancer patientsTiny device could help improve safety, effectiveness of cell therapy for spinal cord injury patients

The study assessed DNA damage in these models following UV irradiation, employing immunohistochemical staining to quantify damage.

Additionally, the effect of UV exposure on radical formation was examined using Electron Paramagnetic Resonance (EPR) spectroscopy, revealing insights into the oxidative stress induced by UV light in different melanin concentrations.

A critical aspect of the research was investigating melanin distribution within the epidermis, utilizing techniques like Fontana-Masson staining and Two-Photon Excited Fluorescence Lifetime Imaging Microscopy (TPE-FLIM).

These methods provided a detailed view of melanin's localization, contributing to understanding its protective versus potential photosensitizing effects. Study results 

After extracting melanin from human epidermis samples and RHE, researchers quantified the total melanin content spectrometrically by measuring absorbance at 500 nm.

In ex vivo skin samples, melanin content varied significantly, correlating strongly with the skin's ITA°, indicating a methodological validation. This approach was then applied to RHE, revealing distinct melanin levels between tanned and light models.

The correlation between melanin content and ITA° was used to categorize RHE models by skin color, confirming the method's applicability across different epidermal sources.

The study further evaluated DNA damage through immunohistochemical staining, quantifying the extent of damage by the presence of cyclobutane-pyrimidine dimers (CPD) in cells post-UVR exposure.

Results showed significant DNA damage across all RHE models immediately after exposure, with variances in damage levels based on the type of UVR and the model's pigmentation.

Notably, tanned RHE models exhibited more damage than light ones, especially after specific types of UV irradiation. This damage assessment highlighted potential photoprotection discrepancies tied to melanin content and distribution.

Additionally, the research investigated radical formation post-irradiation, finding that tanned RHE models produced more free radicals than light models under certain conditions, suggesting melanin's complex role in the skin's response to UV exposure.

Contrary to in vivo skin, where melanin typically encapsulates keratinocyte nuclei, providing a protective barrier, tanned RHE models displayed a non-homogeneous melanin distribution. This misallocation potentially undermines melanin's protective efficacy against UVR.

The examination extended to the melanin coverage within basal cells, revealing a stark contrast between in vivo conditions and tanned RHE models.

In vivo, melanin distribution was relatively uniform across different skin types, whereas tanned RHE showed minimal melanin presence, diverging significantly from expected patterns. This inconsistency underscores a fundamental difference in melanin's protective mechanism in vitro versus in vivo. Conclusions 

To summarize, melanin plays a dual role in the human body, acting as a skin pigment that protects against solar radiation while also exhibiting photosensitizing properties linked to skin pathologies like melanoma.

This complex molecule's protective and harmful effects on the skin are still not fully understood.

Research using reconstructed RHE of tanned and light skin types has sought to delve deeper into melanin's multifaceted roles, examining how melanin content and distribution influence UV-induced DNA damage and the generation of reactive oxygen species (ROS).

These studies have shown that despite higher melanin levels in tanned models suggesting greater protection, all models exhibited significant DNA damage following UV exposure, challenging the notion of melanin's protective efficacy.

The distribution of melanin, particularly its concentration in certain cells and absence in others, may contribute to its photosensitizing effects, leading to increased free radical production and DNA damage.  Journal reference:

Zamudio Díaz, D.F., Busch, L., Kröger, M. et al. (2024) Significance of melanin distribution in the epidermis for the protective effect against UV light. Sci Rep. doi: https://doi.org/10.1038/s41598-024-53941-0. https://www.nature.com/articles/s41598-024-53941-0 

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Politics

Why Boris’s best mate is off to Reform

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Why Boris's best mate is off to Reform

👉Listen to Politics at Sam and Anne’s on your podcast app👈       

Former Conservative chairman and friend of Boris Johnson – Sir Jake Berry – is defecting to Reform UK, causing more problems for Tory leader Kemi Badenoch.

On today’s episode, Sky News’ Sam Coates and Politico’s Anne McElvoy discuss if his defection will divide parts of Reform policy.

Elsewhere, the Anglo-French summit gets under way, with Prime Minister Sir Keir Starmer hoping to announce a migration deal with French President Emmanuel Macron to deter small boat crossings.

Plus, chatter around Whitehall that No10 are considering a pre-summer reshuffle, but will it have any value?

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US

Donald Trump praises Liberian president’s English – the country’s official language

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Donald Trump praises Liberian president's English - the country's official language

Donald Trump has praised the Liberian president’s command of English – the West African country’s official language.

The US president reacted with visible surprise to Joseph Boakai’s English-speaking skills during a White House meeting with leaders from the region on Wednesday.

After the Liberian president finished his brief remarks, Mr Trump told him he speaks “such good English” and asked: “Where did you learn to speak so beautifully?”

Mr Trump seemed surprised when Mr Boakai laughed and responded he learned in Liberia.

The US president said: “It’s beautiful English.

“I have people at this table who can’t speak nearly as well.”

Mr Boakai did not tell Mr Trump that English is the official language of Liberia.

The country was founded in 1822 with the aim of relocating freed African slaves and freeborn black citizens from the US.

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Mr Trump promised the leaders of Liberia, Senegal, Gabon, Mauritania and Guinea-Bissau a pivot from aid to trade at the surprise meeting.

He described the countries as “all very vibrant places with very valuable land, great minerals, and great oil deposits, and wonderful people”.

Read more from Sky News:
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Later asked by a reporter if he’ll visit the continent, Mr Trump said, “At some point, I would like to go to Africa.”

But he added that he’d “have to see what the schedule looks like”.

Trump’s predecessor, President Joe Biden, promised to go to Africa in 2023, but only fulfilled the commitment by visiting Angola in December 2024, just weeks before he left office.

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US

Gaza permanent ceasefire ‘questionable’, says Israeli government

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Gaza permanent ceasefire 'questionable', says Israeli government

The Israeli government believes the chances of achieving a permanent ceasefire in Gaza are “questionable”.

The pessimistic assessment, in a top-level Israeli government briefing given to Sky News, comes as the Israeli Prime Minister prepares to leave Washington DC after a four-day visit which had begun with the expectation of a ceasefire announcement.

Benjamin Netanyahu will leave the US later today with the prospect of even a temporary 60-day ceasefire looking extremely unlikely this week.

Within “a week, two weeks – not a day” is how it was framed in the background briefing late on Wednesday.

Crucially, though, on the chances of the ceasefire lasting beyond 60 days, the framing from the briefing was even less optimistic: “We will begin negotiations on a permanent settlement. But we achieve it? It’s questionable, but Hamas will not be there.”

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Netanyahu arrives in US for ceasefire talks

Sky News has spoken to several Israeli officials at the top level of the government. None will be drawn on any of the details of the negotiations over concerns that public disclosure could jeopardise their chances of success.

But I have been given a very clear understanding of Mr Netanyahu’s thinking.

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The Israeli position is that a permanent ceasefire (beyond the initial 60 days, which itself is yet to be agreed) is only possible if Hamas lays down its arms. “If they don’t, we’ll proceed [with the war],” said a source.

The major sticking point in the talks between Hamas and Israel is the status of the Israel Defence Forces (IDF) inside Gaza during the 60-day ceasefire and beyond, should it last longer.

The latest Israeli proposal, passed to Hamas last week, included a map showing the proposed IDF presence inside Gaza during the ceasefire.

Read more: What is the possible Gaza hostage and ceasefire deal?

Israeli military vehicles stand near the Israel-Gaza border, in Israel.
Pic: Reuters
Image:
Pic: Reuters

This was rejected by Hamas and by Trump’s Middle East envoy, Steve Witkoff, who reportedly told the Israelis that the redeployment map “looks like a Smotrich plan”, a reference to the extreme-right Israeli finance minister, Bezalel Smotrich.

My briefing of Mr Netanyahu’s position is that he has not shifted in terms of Israel’s central stated war aims. The return of the hostages and eliminating Hamas are the key objectives.

But in a hint of how hard it will be to reconcile the differences, it was clear from my briefing that no permanent ceasefire is possible in the Israeli government’s view without the complete removal of Hamas as a political and military entity.

Hamas is not likely to negotiate its way to oblivion.

On the status of the Israeli military inside Gaza, a senior Israeli official told Sky News: “We would want IDF in every square metre of Gaza, and then hand it over to someone.”

Smoke rises in Gaza after an explosion, as seen from the Israeli side of the Israel-Gaza border.
Pic: Reuters
Image:
Pic: Reuters

It was clear to me that Mr Netanyahu wants his stated position to be that his government has no territorial ambition for Gaza.

One quote to come from my briefing, which I am only able to attribute to a senior Israeli official, says: “[We] don’t want to govern Gaza… don’t want to govern, but the first thing is, you have to defeat Hamas.”

Another clear indication of Mr Netanyahu’s position – a quote from the briefing, attributable only to a senior Israeli official: “You cannot have victory if you don’t clear out all the fighting forces.

“You have to go into every square inch unless you are not serious about victory. I am. We are going to defeat them. Those who do not disarm will die. Those who disarm will have a life.”

On the future of Gaza, it’s clear from my briefings that Mr Netanyahu continues to rule out the possibility of a two-state solution “for the foreseeable future”.

The Israeli government assessment is that the Palestinians are not going to have a state “as long as they cling to that idea of destroying our state”.

Read more:
UN Special Rapporteur criticises Israel
Why Netanyahu only wants a 60-day ceasefire
Trump applying ‘heavy pressure’ on Netanyahu

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On the most controversial aspect of the Gaza conflict – the movement of the population – the briefing revealed that Mr Netanyahu’s view is that 60% of Palestinians would “choose to leave” but that Israel would allow them to return once Hamas had been eliminated.

“It’s not forcible eviction, it’s not permanent eviction,” a senior Israeli official said.

Critics of Israel’s war in Gaza say that any removal of Palestinians from Gaza, even if given the appearance of being “voluntary”, is in fact anything but, because the strip has been so comprehensively flattened.

Reacting to Israeli Defence Minister Katz’s recent statement revealing a plan to move Palestinians into a “humanitarian city” in southern Gaza, and not let them out of that area, the official wouldn’t be drawn, except to say: “As a permanent arrangement? Of course not.”

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