reblog

The journey of the human body begins in infancy, often marked by flawless perfection. However, as time elapses and individuals grow, the passage of time become evident on their skin. From minor mosquito bites to major surgical incisions or burns, wounds of varying sizes leave enduring marks on the body. While some wounds heal swiftly, leaving no visible trace, others persist over the years, giving rise to unsightly scars.

Fibrotic scars on the skin typically arise from the healing of wounds in adults. These scars differ from normal skin due to the absence of skin appendages like hair follicles, sebaceous glands, and sweat glands. Moreover, they possess a dense extracellular matrix characterized by parallel fibers. Despite extensive research spanning decades, the achievement of scarless wound healing has remained an elusive goal.

Individuals grappling with scars often resort to scar removal products, often with suboptimal results. Is there a feasible way to facilitate wound healing without the consequential scar tissue formation?

In the realm of modern medicine, the pursuit of scarless wound healing has spurred researchers to explore innovative solutions that harness the body's innate regenerative capabilities. Placental stem cell-derived exosomes, a recent revelation in this field, have opened up promising avenues toward realizing this elusive objective.

A group of scientists has recently published a paper titled "Placental Stem Cells-Derived Exosomes Stimulate Cutaneous Wound Regeneration via Engrailed-1 Inhibition" in the journal Frontiers. Scar formation primarily hinges on the activity of Engrailed-1 (EN1) in fibroblast lineage. By inhibiting the activation of EN1, it is possible to promote wound regeneration and facilitate the reinstatement of skin appendages and microstructures. The study delved into the potential of mesenchymal stem cell (MSC) transplantation to mitigate scar formation.

The researchers uncovered that placental-derived MSCs exhibit a remarkable capacity to expedite wound healing. Notably, these stem cells not only accelerated the pace of wound closure but also enhanced the overall quality of wound healing. This improvement encompassed the regeneration of skin appendages such as hair follicles and sebaceous glands, a reduction in collagen I levels while augmenting collagen III, and the enhancement of collagen patterning (basket-weave structure) within healing skin. Additionally, treatment with placental-derived MSC promoted angiogenesis, underscoring the remarkable potential of wound regeneration through placental MSC-derived exosomes.

Exosomes have displayed functions exceeding initial expectations. Their influence extends beyond merely inhibiting scar tissue growth; they have also found a niche in both exosome diagnostics and therapeutics. These microvesicles hold promise as diagnostic and prognostic markers. The collection of exosomal markers from diverse samples like blood, urine, and saliva offers minimally invasive diagnostic techniques that alleviate patient discomfort.

As scientific progress continues, it is imperative to address ethical considerations and regulatory frameworks pertaining to exosome-based therapies. Functioning as natural carriers of signaling molecules, exosomes as drug carriers offer features such as biocompatibility, circulatory stability, and the ability to penetrate bio-barriers. This paves the way for the development of nanocarriers and cell-mediated drug delivery method. Furthermore, exosome-based drug formulations have demonstrated efficacy in addressing conditions spanning cancer, various infectious diseases, cardiovascular disorders, and neurodegenerative diseases.

In essence, the pursuit of scarless wound healing has yielded remarkable insights into the role of placental stem cell-derived exosomes. These diminutive vesicles not only propel skin regeneration but also harbor the potential to revolutionize diagnostics and therapeutics across multiple medical domains.

For cat lovers, the most tragic thing is probably the cat allergy. As soon as you get close to the cat, you sneeze, have a runny nose, or itchy eyes, skin rashes, and even asthma attacks.

There are many people who are allergic to cats, with about 1 in 10 in the population. In some areas, as many as 30% of the population are allergic to cats.

While enduring allergies, there are many cat slaves who insist on keeping cats. However, there are also some people who have to send their cats away due to severe allergies of themselves or their family members. Either way is painful.

Many people think cat hair is the culprit, but it is not. The real allergen is mainly a protein called Fel d 1 that is secreted through cat's saliva and sebaceous glands. When licking their hair, cats smear this protein all over the body, which is spread into the air through hair and dander, and attaches to carpets, curtains, bed sheets, and clothes and people's hair. Fel d 1 is so sticky that it is difficult to eradicate even after a thorough cleanup. Finding an anti-allergic method targeting Fel d 1 can help most people.

Allergen-specific immunotherapy (AIT) is a tolerance–inducing treatment that changes the natural course of allergic diseases through immune regulation mechanisms.

Recently, researchers from the Luxembourg Institute of Health published an article titled "Comprehensive mapping of immune tolerance yields a regulatory TNF receptor 2 signature in a murine model of successful Fel d 1-specific immunotherapy using high-dose" in the journal Allergy, clarifying that high-dose specific adjuvant molecule CpG oligonucleotides can modulate the immune system's allergic response to the major cat allergen Fel d 1, thereby promoting human tolerance to cat allergic reactions.

In order to study the clinical effect of high-dose CpG adjuvant AIT, researchers first constructed a BALB/c OlaHsd mouse efficacy model allergic to Fel d 1, and then evaluated the efficacy of humans to withstand the maximum CpG dose under endotoxin-free conditions. By detecting the Fel d 1 specific antibodies in the serum of mice, it was found that the allergic mice treated with AIT showed lower IgE levels and higher IgA and IgG (anti-inflammatory effects) attributes, and the lung function and respiratory tract inflammation were obviously improved.

Subsequently, the researchers further studied the cytokines in mouse bronchoalveolar lavage fluid (BALF) and found that compared with untreated allergic mice, the levels of pro-allergic cytokines in mice treated with AIT reduced. This shows that in the preclinical model, AIT can reduce airway inflammation and reduce bronchial hyperresponsiveness.

In addition, the researchers noticed that there were a large number of immune cells involved in allergy regulation and tolerance in the tissues of mice treated with AIT, such as plasmacytoid dendritic cells (pDC), natural killer cells (NKs), and regulatory T cells (T-regs) and regulatory B cells (B-regs), which express high levels of tumor necrosis factor (TNF-α) and tumor necrosis factor receptor (TNFR-2) to inhibit specific immune responses and act as a "brake" on the immune system.

The researchers also found that AIT triggers a new and unique Treg, called biTreg, which can balance the response of effector cells to antigens. This further demonstrates the reversibility of allergic characteristics and the anti-allergic effect of AIT.

To apply these results to the clinic, researchers have developed a subcutaneous (sc) injection drug delivery system, which can reduce the number of airway eosinophils, more effective than traditional Intraperitoneal (IP) Injection, and can inhibit Th2 immune response.

Based on the maximum CpG dose tolerated by humans, the researchers optimized the ATI specific therapy for cat allergy, and developed a medically approved method of administration, laying the foundation for the development of new allergic immunotherapy.

In addition to AIT, scientists are still working on other methods.

1. Prevent cats from producing Fel d 1 by vaccinating them.

2. The antibodies that neutralize allergens are delivered directly into the cat's body through the cat food.

The human body carries a far greater number of symbiotic microorganisms than we can imagine. Cells are the basic units that make up the human body, and the total number of cells in an adult is on the order of tens of trillions. However, the gut flora, which is symbiotic with the human intestinal tract, is ten times the number of cells in the body, and its composition is quite complex, with roughly 500 to 1,000 different species of bacteria in each individual's body.

Among them, gut microorganisms are the main components of the human symbiotic microorganisms. Recent studies have shown that gut microbes affect humans in many ways, including disease, fitness, personality, and even longevity. The interaction between the gut flora and the human body is quite complex, and perhaps we can treat certain intractable diseases, such as cancer, through the gut flora.

On April 6, 2023, researchers from the University of Pittsburgh published a research paper in the journal Cell entitled "Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment".

The study showed that a probiotic, Lactobacillus reuteri, is able to stimulate killer T cells by secreting indole-3-carboxaldehyde (I3A). When mice were fed a tryptophan-rich diet, which is metabolized by Lactobacillus reuteri to I3A, it was able to improve the effectiveness of cancer immunotherapy, suppress tumor size, and prolong survival.

This study lays the groundwork for testing in clinical trials whether I3A treatment or a combination of probiotics and diet can improve cancer immunotherapy outcomes.

The gut is not only an important digestive organ but also the largest immune organ in the body. Since the gut microflora colonizes the human gut, it is easy to assume that the gut flora is likely to be inextricably linked to the human immune system and profoundly influence its function.

In fact, a number of studies in recent years have confirmed that gut microbes are an important influence on the effectiveness of tumor immunotherapy. Recently, a study also found a link between probiotics and immunotherapy responses in melanoma patients.

To understand this process, the research team fed Lactobacillus reuteri, a common probiotic, to germ-free mice with melanoma. The team found that Lactobacillus reuteri metastasized from the gut into the tumor tissue of the mice, where it grew and persisted in the tumors over time.

What's more, mice injected with Lactobacillus reuteri had more CD8+ T-cells (killer T-cells) at the tumor site, the tumors shrank more dramatically, and the mice lived longer compared to control mice. Not only that, but in addition to melanoma, Lactobacillus reuteri inhibited tumor growth in mice with a variety of hormonal tumors, including adenocarcinoma, fibrosarcoma, and breast cancer.

In-depth studies have shown that Lactobacillus reuteri stimulates anti-tumor immune responses through the secretion of indole-3-carboxaldehyde (I3A), a compound that activates the AhR signaling pathway in CD8+ T-cells, promotes their production of interferon gamma, and kills cancer cells. Although this receptor is present in almost every cell in the body, I3A specifically acts on CD8+ T cells to enhance their anti-cancer ability.

Corroborating this, Lactobacillus reuteri no longer induced an anti-tumor immune response when the team removed the AhR receptor from CD8 T cells. In addition, the team used a strain of Lactobacillus reuteri that does not produce I3A, demonstrating that this compound is essential for the bacteria to enhance antitumor immunity and suppress tumors.

It's worth noting that in order to secrete I3A with anti-tumor effects, Lactobacillus reuteri needs to ingest tryptophan, an amino acid found in foods such as chicken, soybeans, oats, nuts, and seeds. When the research team fed tryptophan-rich food to mice with melanoma, their tumors grew more slowly and they lived longer than control mice (whose food was low in tryptophan). In addition, the tryptophan-rich diet also enhanced the tumor-suppressing effects of immunotherapy.

To see if I3A could play a role in human responses to immunotherapy, the team analyzed blood samples from melanoma patients treated with immune checkpoint inhibitors. They found that patients who responded well to immunotherapy had higher levels of I3A, and that higher levels of I3A before treatment were also associated with a better chance of survival.

"Based on these findings, it is likely that I3A levels will be used in the future as a biomarker to predict which patients are likely to respond to immunotherapy and that I3A will also be used as an adjuvant to immunotherapy to improve the prognosis of patients," according to Professor Marlies Meisel, the corresponding author of the study.

The findings are still in the early stages, and further studies are needed to confirm them, including clinical trials, to see if a tryptophan-rich diet actually affects the prognosis of tumor patients.

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