Scientists capture macrophages immune cells attacking live melanoma

Good news! Cancer is history (soon)!

"... a previously overlooked population of immune cells called macrophages that patrol the edges of melanoma tumours, steadily engulfing cancer cells and slowing tumour growth. ...

“This is the first time anyone has captured a macrophage attacking and engulfing a live cancer cell in real time,” ..."

From the abstract:

"Macrophages in the skin reside in multiple distinct layers and perform various functions. Here, we show that CD169+ macrophages reside in the hypodermis and comprise the major skin myeloid cell population in the steady state.

In a syngeneic melanoma model, CD169+ macrophages encapsulate growing melanomas and directly suppress their growth.

CSF1R blockade depleted CD169+ macrophages in tumors and resulted in unrestrained growth.

This local containment of tumor growth in the skin was independent of CD169+ subcapsular sinus macrophages in the tumor-draining lymph node and did not require B or T cells.

Intravital imaging revealed engulfment and ingestion of live tumor cells by CD169+ macrophages.

This phagocytosis did not require the phosphatidylserine receptor MERTK. CD169+ macrophages are also enriched in the hypodermis in skin biopsies from healthy human skin and melanoma.

These data identify tissue-resident CD169+ macrophages as a potential cellular target to achieve innate immune containment and reinforce adaptive immune control of tumors."

Garvan scientists capture ‘housekeeping’ immune cells attacking live melanoma | Garvan Institute of Medical Research "Macrophage immune cells were imaged engulfing live cancer cells – opening a new approach for melanoma treatment."

CSF1R-dependent CD169-positive macrophages locally constrain melanoma growth in the skin

A highly magnified view of melanoma tumours growing in the skin. CD169+ macrophages are shown in green and yellow forming a biological boundary wall to contain the tumours.

Fig. 2 Skin CD169+ macrophages suppress B16-F10 melanoma growth.

Fig. 4 Skin CD169+ macrophages ingest tumor cells.

New Burn Treatment with exosomes Improves Recovery from Fire Injuries

Good news!

On my recent trip to China, I have seen a Chinese man walking in the streets with very serious and large burn scars in his face. It looked horrible!

This treatment was performed by a highly cited doctor: Marc G. Jeschke

"... a groundbreaking treatment using exosomes, which are tiny particles released by cells that help coordinate healing, tissue repair and reduce inflammation…

Exosomes have been studied for years in burn research but had never before been used in a human burn patient ... While the particles have shown promise in other wound-healing applications, ... became the first person in the world to receive the treatment for burns …"

"[patient]’s face suffered deep partial to full thickness burns, meaning these were serious injuries that most likely would have resulted in skin grafts. Her neck fared worse, with full thickness burns that destroyed all skin layers. ..."

New Burn Treatment Improves Recovery from Fire Injuries - Human Progress

World-first burn treatment helps Western student recover from injuries suffered in frat house fire "Hamilton doctors used experimental exosome therapy to avoid skin grafts after severe facial burns"

HHS performs world-first burn treatment with incredible results (original news release)

What a difference!

Study suggests healing skin without scarring may be possible

Good news!

"... The new study published March 20 in Cell reveals a way to fully regenerate skin by unblocking an embryonic healing mechanism that shuts off after birth. Demonstrated on mice, the strategy may help guide the development of similar therapies for human patients. ...

In mice wounded three days before birth, the skin regenerated diverse cell types and closely resembled unwounded skin.

But when wounded at five days after birth, the site was covered by epithelial cells and became packed with collagen scar tissue and abnormally dense nerve fibers and immune cells. Many other skin cell types failed to regrow. ...

They found that postnatal wound sites became densely packed with nerves. This “hyperinnervation” occurs because fibroblasts in postnatal wounds upregulate the gene Cxcl12, which recruits excessive nerves to the area and impairs the regrowth of other skin-cell types.

When researchers depleted Cxcl12 in wounds in postnatal mice, “hyperinnervation” was curtailed, and the skin regrew diverse cell types. Blocking local nerve signaling with botulinum toxin A (Botox) produced similar effects. ..."

From the highlights and abstract:

"Highlights

• Embryonic skin regenerates diverse cell types after injury, whereas postnatal skin does not

• Postnatal wounds have wound-specific fibroblasts that drive hyperinnervation via CXCL12

• Excessive innervation at the wound site blocks multilineage regeneration

• Reducing hyperinnervation restores multilineage regeneration after postnatal injury

Summary

Some mammalian tissues can replace lost cells within one lineage, but organ-level regeneration—restoring diverse cell types across lineages—remains rare. Here, we show that late embryonic full-thickness skin injuries heal by regenerating epithelial, mesenchymal, neuronal, and vascular tissues with proper connectivity. However, this ability is lost soon after birth, resulting in failure to restore most cell types and hyperinnervation within the wound bed. Single-cell sequencing identified a postnatal wound-specific fibroblast (PWF) population absent after embryonic wounding. Through an in vivo screen, we discovered that three PWF-enriched genes—Timp1, Cxcl12, and Ccl7—inhibit organ-level regeneration and cause hyperinnervation when overexpressed in embryonic wounds. Reducing hyperinnervation in postnatal wounds through the depletion of Cxcl12 in fibroblasts or nerve ablation enables regeneration of diverse lineages after injury. Our study identifies mechanisms that transition an organ from regenerative to non-regenerative, discovers fibroblast-driven hyperinnervation as a key barrier, and demonstrates that removing this barrier unlocks organ-level regeneration.

"

Study suggests healing skin without scarring may be possible — Harvard Gazette "Researchers unblock embryonic regrowth mechanism that shuts down after birth in mice"

Hyperinnervation inhibits organ-level regeneration in mammalian skin (open access)

Graphical abstract

Figure 1 Multilineage regeneration differs between embryonic and postnatal wounding

These mysterious ridges could be the secret to younger skin

Recommendable!

Scientists now know how melanoma skin cancer evolves to resist immunotherapy

Good news! Cancer is history (soon)!

"... The team found that relapsing melanoma tumors often acquire genomic DNA copy-number variants, which delete or amplify sections of DNA. These variants frequently affect genes that control cancer cells’ ability to self-destruct in response to damage caused by immune attacks. The cumulative effect of copy-number changes, often involving multiple cell-death genes, allows cancer cells to survive immune attacks, leading to tumors relapsing or regrowing months or years after the initial therapy-induced tumor shrinkage. ..."

From the highlights and abstract:

"Highlights

• Acquired-resistant melanomas amplify anti-apoptotic and/or delete pro-apoptotic genes

• Models of acquired ICI resistance recapitulate apoptotic evasion due to CNVs

• Preexisting and de novo resistance-driver CNVs occur commonly or privately in subclones

• Lowering the apoptotic threshold salvages ICI sensitivity and prevents relapse

Summary

Patients who initially respond to immune checkpoint inhibitors (ICIs) often relapse.

Here, we studied how disease-progressive (DP) clinical melanomas evolve genomically to acquire ICI resistance. 

Compared to patient-matched pretreatment tumors, DP tumors recurrently amplified and/or deleted anti-apoptotic and/or pro-apoptotic genes, respectively.

By chronic exposure to killer T cells or ICI therapy, we derived acquired-resistant (AR) human melanoma cell lines and murine melanoma tumors that recapitulate co-occurrent copy-number variants (CNVs) of apoptotic genes observed in DP melanomas. 

AR and DP subclones expanded shared, private, and, in some subclones, preexistent driver CNVs. Compared to isogenic parental cells, AR melanoma cells attenuated apoptotic priming but, with overexpression of deleted pro-apoptotic genes, recovered mitochondrial priming and sensitivity to killer T cells or ICIs.

In mice, pharmacologically reducing the apoptotic threshold of ICI persisters prevented relapses.

Thus, CNVs can drive the evolution of resistance to ICIs in melanoma, with tumor cell-intrinsic apoptotic threshold representing a target to curtail persister evolution."

Scientists now know how melanoma skin cancer evolves to resist immunotherapy | UCLA "Following the discovery, researchers have identified a strategy to possibly prevent treatment relapses"

Genomic copy-number variants drive apoptotic evasion underlying acquired resistance to immune checkpoint inhibitors (open access)

Graphical abstract:

Unlocking the Skin’s Natural Healing Power

Amazing stuff!

"Key points

• The skin has an amazing ability to regenerate and heal.
• Researchers have uncovered one of the earliest steps in how skin stem cells learn to repair tissue.
• The findings could inform the development of skin healing methods, including for organ repair and skin transplants.

...

discovered that, during the earliest stages of embryonic development, skin stem cells contribute to forming a protective skin layer that accelerates healing as the embryo grows.

Their findings reveal one of the earliest steps in how skin stem cells learn to repair tissue ...

The researchers examined development in zebrafish embryos, the skin organization of which is similar to human embryos. Specifically, they analyzed the thin transparent layer of cells that lines the zebrafish fin folds in the embryo, structures that transition into fins during development in a process that’s similar to limb development in mammals. ...

compared their findings in the embryonic zebrafish fin fold to a bilayer model of the human epidermis. Their modeling revealed that collagen and laminin matrices similarly influence human skin cells. Specifically, they found that laminin inhibited the proteins that drive desmosome junction formation. ..."

From the abstract:

"Epidermal stem cells interact with the extracellular matrix (ECM) to regulate their differentiation and maintain skin architecture.

Here, we demonstrate a role for basal epidermal stem cells (BECs)-ECM interaction in regulating adhesion molecules expressed by the periderm—the superficial epidermal cells (SECs) of the embryonic bilayered skin.

Using the developing zebrafish fin fold, we identify BECs form distinct regions of collagen- versus laminin- enriched basement membranes through integrin-mediated adhesions.

Mechanistically, collagen-associated BECs form desmosomes and adherens junctions (AJs) with SECs while laminin-associated BECs display reduced desmosomes but sustain AJs and actomyosin expression with SECs.

Notably, we show both in vivo and in a bilayered human keratinocyte model, that laminin, compared to collagen, is sufficient to repress desmosome formation while sustaining AJs specifically at the interlayer cell contacts.

In vivo, laminin deficiency enhances desmosome expression across layers and impairs the wound-healing capacity of SECs. This defect was partially rescued by genetic reduction of the desmosome protein Desmoplakin-1a, highlighting the role of ECM-dependent junctional specialization in mediating differences in SEC injury response.

Overall, our findings identify that stem cells, through their matrix, establish specialized junctions in the overlying stratified epithelium, which contribute to skin healing properties."

Unlocking the Skin’s Natural Healing Power < Yale School of Medicine

Epidermal stem cells control periderm injury repair via matrix-driven specialization of intercellular junctions (open access)

Fig. 1: Region-Specific Junctional and Cytoskeletal Organization of BECs in the Fin Fold.

Kosmetik der Zukunft: Anti-Aging-Gesichtsmaske stimuliert eigene Kollagenproduktion

Na sowas! Die Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. ist auch in der Kosmetik tätig!

Anti-Aging-Gesichtsmaske stimuliert eigene Kollagenproduktion "Eine bioabbaubare Gesichtsmaske als Zweikomponentensystem, die die Kollagenproduktion stimuliert und so zu einer nachhaltigen Hautverjüngung führen soll, haben Forschende des Fraunhofer-Translationszentrums für Regenerative Therapien TLZ-RT am Fraunhofer-Institut für Silicatforschung ISC gemeinsam mit der B-COS GmbH entwickelt. Ausgelöst wird der Anti-Aging-Effekt durch Orthokieselsäure."

War die Autorin des Artikels auch ein Versuchskaninchen?

How psychological stress increases the risk of bacterial skin infection via defective responses

Amazing stuff!

"... Now, new experiments in mice have revealed that stress makes it harder for certain skin cells to fight off bacteria—leaving the animals vulnerable to more severe infection with Staphylococcus aureus.

To induce stress, scientists confined the mice inside small tubes for three hours a day on three consecutive days, exposing them to S. aureus upon release. The restrained rodents produced more adrenaline, leading to higher levels of a stress-related protein called TGFβ. This protein interferes with specialized skin cells known as dermal fibroblasts and prevents them from making cathelicidin—an antimicrobial molecule that normally plays a key role in the skin’s defense system. As a result, the restrained mice ended up experiencing more severe infections, characterized by larger lesions. Blocking adrenaline or TGFβ, meanwhile, allowed the animals’ skin cells to mount a stronger defense against the bacteria."

From the editor's summary and abstract:

"Editor’s summary

Psychological stress affects multiple systems in mammals and is linked with greater susceptibility to bacterial infections. Chan et al. used a mouse model to show that psychological stress causes an impaired response to Staphylococcus aureus infection.

The defective response was associated with decreased dermal adipogenesis by fibroblasts and decreased production of the antimicrobial peptide cathelicidin (Camp) by these cells, thus enhancing susceptibility to S. aureus.

This brain-skin axis triggered by stress was mediated by adrenergic signaling and the production of TGFβ. These were critical for infection given that inhibiting adrenergic or TGFβ signaling restored normal host defense to S. aureus in stressed mice. ...

Abstract

Infections after psychological stress are a major health care problem.

Single-cell transcriptomics and lipidomic profiling in a mouse model of stress show that dermal fibroblasts undergoing adipogenesis have defective responses to Staphylococcus aureus skin infection.

Adrenalectomy or adrenergic inhibition restores the fibroblast adipogenic response to S. aureus and enables mice to effectively resist infection during stress. Increased susceptibility to S. aureus from stress is attributed to suppression of the antimicrobial peptide cathelicidin (Camp) because adrenaline directly inhibits Camp production by fibroblasts, and mice lacking Camp in fibroblasts do not increase infection after stress.

Transforming growth factor β (TGFβ) is induced by stress and adrenergic signaling, and inhibition of TGFβ or deletion of the TGFβ receptor on fibroblasts increases Camp expression and restores protection against infection.

Together, these data show that stress initiates a brain-skin axis mediated by TGFβ that impairs the immune defense function of dermal fibroblasts to produce the Camp antimicrobial peptide."

ScienceAdviser

Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts (open access)

Fig. 1. Psychological stress exacerbates skin infection by SA [Staphylococcus aureus].

Cells lining your skin and organs can generate electricity when injured − potentially opening new doors to treating wounds

Amazing stuff! If only Michael Faraday knew! 😊

"... As bioengineers, we became interested in the epithelial cells that make up human skin and the outer layer of people’s intestinal tissues. These cells aren’t known to be able to generate bioelectricity. Textbooks state that they primarily act as a barrier against pathogens and poisons; epithelial cells are thought to do their jobs passively, like how plastic wrapping protects food against spoilage.

To our surprise, however, we found that wounded epithelial cells can propagate electrical signals across dozens of cells that persist for several hours. In this newly published research, we were able to show that even epithelial cells use bioelectricity to coordinate with their neighbors when the emergency of an injury demands it. Understanding this unexpected twist in how the body operates may lead to improved treatments for wounds. ..."

From the abstract:

"Epithelial cells (human keratinocyte cells and the canine MDCK cell line), traditionally viewed as electrically non-self-excitable and involved primarily in physiological functions such as barrier presentation, absorption, secretion, and protection, are shown here to exhibit traveling extracellular electric charge when they recover from spatially focused, laser-induced wounding of confluent monolayers cultured on a multielectrode array chip.

Voltage spikes measured on these electrodes display depolarization, repolarization, and hyperpolarization phases with amplitudes similar to the action potentials of neurons but with the markedly slower duration of 1 to 2 s.

Some propagate distances up to hundreds of μm from the wound with a mean speed of around 10 mm s−1.

Generation and transmission of bioelectric signals are significantly influenced by the perturbation of mechanosensitive cationic ion channels. These direct measurements confirm bioelectric signaling that previous work has hypothesized to regulate epithelial cell development and may have relevance to the frequency parameter selection of bioelectric devices."

Cells lining your skin and organs can generate electricity when injured − potentially opening new doors to treating wounds

Electric spiking activity in epithelial cells (open access)

Fig. 1. Wounded epithelial cell monolayers display traveling voltage spikes.

Yes, tiny mites live on your face — but is that a bad thing?

If it was not a cartoon, it would be a horror video!

Discovering how fat cells play a protective role in skin fibrosis development

Good news!

"... In a new study, Yale researchers have started to uncover what happens at the cellular and molecular levels as skin fibrosis progresses, and the findings, they say, yield potential targets for treating fibrotic diseases in the future. ...

the researchers found that adipocyte depletion happens quite early in the fibrotic process.

Adipocytes in the skin contain one large liquid droplet of fat molecules (or lipids), which can be released from the cell in response to various biological events. In the two mouse models of skin fibrosis used in the new study, the researchers observed that adipocytes in the area where fibrosis was stimulated lost their lipid droplets as early as five days into fibrosis development.

When the researchers stopped fibrosis stimulation, they saw that the adipocytes refilled with lipids as the skin began to recover. ..."

From the abstract:

"During skin fibrosis, extracellular matrix (ECM) proteins are overproduced, and resident lipid-filled, mature dermal adipocytes are depleted in both human disease and mouse models. However, the mechanisms by which the reduction in lipid-filled adipocytes occurs during fibrosis are not well understood.

Here, we identify that adipocyte lipolysis via the rate limiting enzyme, adipocyte triglyceride lipase (Atgl), is required for loss of adipose tissue during skin fibrosis in mice. We find that in two fibrotic mouse models, adipocyte lipolysis occurs early during skin fibrosis development and lipid storage is reestablished during fibrosis recovery.

In mice lacking Atgl in adipocytes, maintenance of adipocyte lipid storage occurs in both chemical and genetic models of fibrosis development. Transcriptional analysis revealed upregulation of lipid metabolism/lipolysis genes in fibrotic patient skin.

Interestingly, loss of adipocyte Atgl-driven lipolysis results in precocious, fibrotic remodeling of the dermal ECM in bleomycin treated mice as indicated by histological and transcriptional changes. These data suggest that dermal adipocyte-derived fatty acids prevent fibrotic ECM remodeling in fibroblasts during fibrosis development.

Thus, we suggest that dermal adipocyte-derived fatty acids are released during fibrosis development and delay fibroblast fibrogenic responses, which may hold therapeutic potential for treating fibrotic diseases."

Fat cells play a protective role in fibrosis development | Yale News "People with skin fibrosis experience a painful thickening of the skin, for which there is no treatment. Findings from a Yale study may point the way."

Atgl-dependent adipocyte lipolysis promotes lipodystrophy and restrains fibrogenic responses during skin fibrosis (open access)

Figure 3 Fibrotic lipodystrophy requires Atgl expression in adipocytes.

The Skin has its own immune system

Amazing stuff!

"The skin seems to produce its own antibodies to keep microbes in check. ... In mice colonized by Staphylococcus epidermidis, a common and harmless bacterium found on human skin, the skin was able to generate antibodies even when other parts of the immune system were disabled. And this surprise power might be harnessed to fight pathogens: when researchers modified S. epidermidis to display part of the tetanus toxin, the skin response protected mice from a lethal dose."

"The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections, a pair of studies reports in Nature this week. The findings could pave the way for the development of needle-free vaccines that can be applied to the skin."

"... The initial experiments ... were simple: Dip a cotton swab into a vial containing S. epidermidis. Rub the swab gently on the head of a normal mouse ... and put the mouse back in its cage. Draw blood at defined time points over the next six weeks, asking: Has this mouse’s immune system produced any antibodies that bind to S. epidermidis?

The mice’s antibody response to S. epidermidis was “a shocker,” ...“Those antibodies’ levels increased slowly, then some more – and then even more.” At six weeks, they’d reached a higher concentration than one would expect from a regular vaccination – and they stayed at those levels. ..."

From the abstract (1):

"The ubiquitous skin colonist Staphylococcus epidermidis elicits a CD8+ T cell response pre-emptively, in the absence of an infection. However, the scope and purpose of this anti-commensal immune program are not well defined, limiting our ability to harness it therapeutically. Here, we show that this colonist also induces a potent, durable, and specific antibody response that is conserved in humans and non-human primates. A series of S. epidermidis cell-wall mutants revealed that the cell surface protein Aap is a predominant target.

By colonizing mice with a strain of S. epidermidis in which the parallel β-helix domain of Aap is replaced by tetanus toxin fragment C, we elicit a potent neutralizing antibody response that protects mice against a lethal challenge.

A similar strain of S. epidermidis expressing an Aap-SpyCatcher chimera can be conjugated with recombinant immunogens; the resulting labeled commensal elicits high antibody titers under conditions of physiologic colonization, including a robust IgA response in the nasal and pulmonary mucosa. Thus, immunity to a common skin colonist involves a coordinated T and B cell response, the latter of which can be redirected against pathogens as a novel form of topical vaccination."

From the abstract (2):

"The microbiota colonizes each barrier site and broadly controls host physiology. However, when uncontrolled, microbial colonists can also promote inflammation and induce systemic infection. The unique strategies employed at each barrier tissue to control the coexistence of the host with its microbiota remain largely elusive. Here we uncover that, within the skin, host-microbiota symbiosis depends on the remarkable ability of the skin to act as an autonomous lymphoid organ. Notably, an encounter with a new skin commensal promotes two parallel responses, both under the control of Langerhans cells.

On one hand, skin commensals induce the formation of classical germinal centers within the lymph node associated with IgG1 and IgG3 antibody responses.

On the other hand, microbial colonization also leads to the development of tertiary lymphoid organs within the skin that can locally sustain IgG2b and IgG2c responses.

These phenomena are supported by the ability of regulatory T cells to convert into T follicular helper cells. Skin autonomous production of antibodies is sufficient to control local microbial biomass, as well as subsequent systemic infection with the same microbe. Collectively, these results reveal a striking compartmentalization of humoral responses to the microbiota allowing for control of both microbial symbiosis and potential pathogenesis."

Nature Briefing: Translational Research

The skin’s ‘surprise’ power: it has its very own immune system (no public access) "The finding could lead to the development of needle-free vaccines."

Stanford scientists transform ubiquitous skin bacterium into a topical vaccine (original news release) "Findings in mice could translate into a radical, needle-free vaccination approach that would also eliminate reactions including fever, swelling and pain."

Discovery and engineering of the antibody response to a prominent skin commensal (1; no public access, but first article above contains link to PDF, bioRxiv link)

Skin autonomous antibody production regulates host-microbiota interactions (2; no public access, but first article above contains link to PDF)

Detailed study and map reveals how cells coordinate to heal human wounds at all phases

Good news!

"A new study ... maps the cellular and molecular dynamics of human wound healing in exceptional detail. ...

They used advanced single-cell RNA sequencing and spatial transcriptomics techniques to track how cells and molecules change over time.

"We have discovered that an important protein, FOSL1, helps skin cells to move and cover wounds during the healing process. We have also seen that certain other cells, such as macrophages and fibroblasts, help these skin cells to move and repair the damage," ...

"When we compared wounds from people with chronic diseases, such as venous ulcers and diabetic foot ulcers, we found that problems with cell movement can make healing more difficult," ..."

"Self-healing of wounds is vital, but little is known about how cells cooperate during this process. To better understand this, researchers studied skin and wounds from the same individuals at different phases of healing: inflammation, proliferation, and remodeling.  ...

This breakthrough sheds light on why some wounds fail to heal effectively. Through a detailed comparison between chronic and acute wounds, the researchers uncovered impaired inflammatory responses and cellular migration capability, suggesting targeted approaches to overcome these healing barriers.  ..."

From the highlights and abstract:

"Highlights

• A spatiotemporal atlas to explore human in vivo gene expression across wound healing

• Wound margin architecture unveils a model for human re-epithelialization

• Distinct healing challenges in venous ulcers and diabetic foot ulcers

• Unique human healing traits emerge in cellular heterogeneity and gene expression

Summary

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization. It shows that pro-inflammatory macrophages and fibroblasts sequentially support keratinocyte migration like a relay race across different healing stages. Comparison with single-cell data from venous and diabetic foot ulcers uncovers a link between failed keratinocyte migration and impaired inflammatory response in chronic wounds. Additionally, comparing human and mouse acute wound transcriptomes underscores the indispensable value of this roadmap in bridging basic research with clinical innovations."

Detailed study reveals how cells coordinate to heal human wounds

New study reveals new insights into wound healing (original news release) "A new study from Karolinska Institutet maps the cellular and molecular dynamics of human wound healing in exceptional detail. The study was published in Cell Stem Cell."

Spatiotemporal single-cell roadmap of human skin wound healing (open access)

Graphical abstract

Figure 1. A spatiotemporal map of human skin wound healing

The world's first octopus-inspired superior sunscreen (and possibly anti aging) is on its way

Good news!

"A unique material inspired by a pigment in the skin of octopus, squid and cuttlefish has been harnessed to boost the skin-protecting active ingredients in sunscreen, as well as providing a shield against skin damage. And while it comes with all the benefits to humans, including antioxidant properties, it's harmless to the environment, which could revolutionize not just sun protection but skincare in general. ...
In the latest study, the scientists shows how a synthesized version of xanthommatin can significantly boost sunscreen protection levels when blended with zinc oxide, without having any negative impact on marine life such as corals or to humans. ..."

From the abstract:

"Objective

... We describe the use of a natural product, Xanthochrome® (INCI: Ammonium Xanthommatin), in a series of studies designed to not only assess its safety with marine systems but also its formulation compatibility and function in water-in-oil mineral sunscreens. Xanthochrome is the synthetic form of the naturally occurring chromophore xanthommatin (XA) present in cephalopod skin, which doubles as a photostable antioxidant; however, it has never been explored in combination with mineral UV filters in finished formulations.

Methods

Given the recent controversies associated with the environmental toxicological effects of some chemicals used in sunscreens, the safety of XA with coral cuttings was first validated at concentrations 5× above those used in our formulations. Next, a particle-based delivery of XA was designed and incorporated into a zinc oxide (ZnO)-based water-in-oil sunscreen, where the SPF, critical wavelength, and visible light (VL) blocking potential were measured.

Results

We observed no adverse effects of XA at 100 mg/L when tested with coral cuttings, ... When formulated with ZnO-based sunscreens, the inclusion of XA increased the total UV absorbance profile by 28% and the total blocking potential of VL by 45%. The formulations also elicited no dermal irritation or sensitization in a human insult repeat patch test (N = 100 subjects).

Conclusions

XA is differentiated as a photostable, water-soluble compound that is a VL booster proven safe for skin and coral cuttings. To the best of our knowledge, there are no other boosters that can be classified as such, despite a growing body of literature highlighting the need in the industry."

The world's first octopus-inspired superior sunscreen is on its way

Octopus and squid pigments enhance sunscreen without harming the environment, Northeastern researchers and company founders say (original news release)

Using cephalopod-inspired chemistry to extend long-wavelength ultraviolet and visible light protection of mineral sunscreens (no public access)

Professor Leila Deravi and grad Camille Martin, co-founders of Seaspire, isolated anti-aging and sun protective qualities of octopus and squid.

Hair-loss hope: Natural sugar stimulates significant regrowth and it is cheap

Good news! Maybe too late for me? 😊

"... An international team of scientists ... found that the organic compound 2-deoxy-D-ribose (2dDR) can stimulate new hair growth, following eight years of research into how this deoxy sugar could assist wound healing. The accidental discovery came about when they saw how hair around wound patches was showing accelerated growth, compared to non-treated areas. They believed it was having a direct impact on ailing hair follicles. ..."

From the abstract:

"Androgenic alopecia (AGA) affects both men and women worldwide. New blood vessel formation can restore blood supply and stimulate the hair regrowth cycle. Recently, our group reported that 2-deoxy-D-ribose (2dDR) is 80%–90% as effective as VEGF in the stimulation of neovascularization in in vitro models and in a chick bioassay. In this study, we aimed to assess the effect of 2dDR on hair growth. We prepared an alginate gel containing 2dDR, polypropylene glycol, and phenoxyethanol. AGA was developed in C57BL6 mice by intraperitoneally injecting testosterone (TE). A dihydrotestosterone (DHT)-treated group was used as a negative control, a minoxidil group was used as a positive control, and we included groups treated with 2dDR gel and a combination of 2dDR and minoxidil. Each treatment was applied for 20 days. Both groups treated with 2dDR gel and minoxidil stimulated the morphogenesis of hair follicles. H&E-stained skin sections of C57BL/6 mice demonstrated an increase in length, diameter, hair follicle density, anagen/telogen ratio, diameter of hair follicles, area of the hair bulb covered in melanin, and an increase in the number of blood vessels. Masson’s trichrome staining showed an increase in the area of the hair bulb covered in melanin. The effects of the FDA-approved drug (minoxidil) on hair growth were similar to those of 2dDR (80%–90%). No significant benefit were observed by applying a combination of minoxidil with 2dDR. We conclude that 2dDR gel has potential for the treatment of androgenic alopecia and possibly other alopecia conditions where stimulation of hair regrowth is desirable, such as after chemotherapy. The mechanism of activity of 2dDR remains to be established."

Hair-loss hope: Natural sugar stimulates significant regrowth

Stimulation of hair regrowth in an animal model of androgenic alopecia using 2-deoxy-D-ribose (open access)

Figure 2.

(A) Schematic illustration of the in vivo experiment.

(B) Comparison of dorsal hair regeneration ...

(C) Mouse skin color score index.

(D) Graphical representation of skin color scored by different treatment groups at various time intervals ...

Hair loss prevented by blocking ancient biological mechanism

Have we maybe finally found a solution to deal with scalp hair loss?

"... scientists have linked one of the ways  that cells respond to stressful conditions with restricted healthy hair growth.

The ... team unexpectedly discovered the link in a lab experiment where they were testing a drug to see if it cultivates human scalp hair follicles in a dish.

The study inadvertently led to a link to the cellular stress response - an ancient biological mechanism which occurs across life from yeast and roundworms through to humans.

The team hope that by targeting the pathway, treatments for hair loss might one day be found.
Known in full as the Integrated Stress Response-  or ISR-  it is triggered in stressful cellular conditions such as poor nutrient availability, viral infection, or when there is a build-up of misshaped proteins in cells. ...

ISR is already the subject of great interest to scientists studying cancer, neurodegenerative disorders and ageing. ..."

From the abstract:

"Unravelling how energy metabolism and stress responses are regulated in human scalp hair follicles could reveal novel insights into the controls of hair growth and provide new targets to manage hair loss disorders. The Mitochondrial Pyruvate Carrier (MPC) imports pyruvate, produced via glycolysis, into the mitochondria, fuelling the TCA cycle. Previous work has shown that MPC inhibition promotes lactate generation, which activates murine epithelial hair follicle stem cells (eHFSCs). However, by pharmacologically targeting the MPC in short-term human hair follicle ex vivo organ culture experiments using UK-5099, we induced metabolic stress-responsive proliferative arrest throughout the human hair follicle epithelium, including within Keratin 15+ eHFSCs. Through transcriptomics, MPC inhibition was shown to promote a gene expression signature indicative of disrupted FGF, IGF, TGFβ and WNT signalling, mitochondrial dysfunction, and activation of the integrated stress response (ISR), which can arrest cell cycle progression. The ISR, mediated by the transcription factor ATF4, is activated by stressors including amino acid deprivation and ER stress, consistent with MPC inhibition within our model. Using RNAScope, we confirmed the upregulation of both ATF4 and the highly upregulated ATF4-target gene ADM2 on human hair follicle tissue sections in situ. Moreover, treatment with the ISR inhibitor ISRIB attenuated both the upregulation of ADM2 and the proliferative block imposed via MPC inhibition. Together, this work reveals how the human hair follicle, as a complex and metabolically active human tissue system, can dynamically adapt to metabolic stress."

Hair loss prevented by blocking ancient biological mechanism A surprise result in a lab experiment has led to the discovery of an ancient biological stress pathway that can trigger cells to stop making what's needed to grow hair. Scientists believe this opens the door to developing a pre-emptive strike, protecting hair follicles from this process and preventing hair loss.

Surprising link between ancient biology and restricted human hair growth found (original news release)

Activation of the integrated stress response in human hair follicles (open access)

A healthy hair follicle (left), and one inhibited by a drug that triggered the ISR mechanism preventing hair growth

I couldn’t escape poison oak. So I started eating it.

Does this really help to desensitize oneself? Or is this just a case of California dreaming?

"The taste of young poison oak is surprisingly mild, grassy and only a little bit tart. That is what writer Jeff Horwitz found when he started eating it. Where he lives, in Northern California, poison oak is a native plant that is impossible to avoid if you enjoy hiking, camping and foraging. The most conventional treatment for exposure is to promptly lather up with dish soap or Tecnu, a specialized cleanser. There was, however, a different approach to desensitizing people who are allergic to poison ivy and oak. And it had a track record of success dating back hundreds of years."

I couldn’t escape poison oak. So I started eating it.

Genetic mutation that causes psoriasis has been identified

Good news!

"... People with psoriasis have overactive immune systems that cause them to develop red, scaly, and itchy patches across their body. More than 4.6 million people were living with psoriasis globally in 2019.

This world first discovery also identified what drives the skin-only disease to occasionally progress to a skin and joint disease known as psoriatic arthritis.   ...

The mutation in the IKBKB gene is what’s known as a gain-of-function mutation.

They found that mice with a single copy of the mutated IKBKB gene developed a skin disease with characteristics of psoriasis. While those with two copies of the mutation resulted in psoriatic arthritis. ..."

From the abstract:

"Loss-of-function mutations have provided crucial insights into the immunoregulatory actions of Foxp3+ regulatory T cells (Tregs). By contrast, we know very little about the consequences of defects that amplify aspects of Treg function or differentiation. Here we show that mice heterozygous for an Ikbkb gain-of-function mutation develop psoriasis. Doubling the gene dose (IkbkbGoF/GoF) results in dactylitis, spondylitis, and characteristic nail changes, which are features of psoriatic arthritis. IkbkbGoF mice exhibit a selective expansion of Foxp3 + CD25+ Tregs of which a subset express IL-17. These modified Tregs are enriched in both inflamed tissues, blood and spleen, and their transfer is sufficient to induce disease without conventional T cells. Single-cell transcriptional and phenotyping analyses of isolated Tregs reveal expansion of non-lymphoid tissue (tissue-resident) Tregs expressing Th17-related genes, Helios, tissue-resident markers including CD103 and CD69, and a prominent NF-κB transcriptome. Thus, IKK2 regulates tissue-resident Treg differentiation, and overactivity drives dose-dependent skin and systemic inflammation."

Genetic mutation that causes psoriasis has been identified

IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model (open access)

Fig. 1: Overactive IKK2 leads to psoriasis.

Study Uncovers Hidden Ingredients in 83% of Tattoo Inks, Raising Concerns

This or similar results have been repeatedly reported over several decades! 

In my opinion, the more of the body's skin tattoos are covering, the more annoying it usually looks, while a few small tattoos may look appealing. Perhaps, I am too old fashioned!  😊

If I am not mistaken then tattooing is a largely unregulated business in many Western countries. As long as the number of customers was fairly small this was not too much of a concern.

"... While 32 percent of adults in the United States have at least one, many of the inks in the United States today used to decorate people's skin are more of a motley mixture than a precise blend, a new study has found. ..."

From the abstract:

"As tattoos continue to rise in popularity, the demand for tattoo ink has surged. Historically, tattoo inks have been underregulated in the US market. This study analyzes inks from nine different brands that are common in the United States, ranging from major to small manufacturers. Out of 54 inks, 45 contained unlisted additives and/or pigments. Major, unlisted adulterants include poly(ethylene glycol), propylene glycol, and higher alkanes. Many of the adulterants pose possible allergic or other health risks. Taken together, the results from this study highlight the potential for a significant issue around inaccurate tattoo ink labeling in the United States."

Study Uncovers Hidden Ingredients in 83% of Tattoo Inks, Raising Concerns : ScienceAlert

What’s in My Ink: An Analysis of Commercial Tattoo Ink on the US Market (no public access)

What Causes Itch?

Good news! Scientists at Harvard Medical School have shown for the first time that a common skin bacterium — Staphylococcus aureus — can cause itch by acting directly on nerve cells.