Mao-Qiang Man’s research while affiliated with Southern Adventist University and other places

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Publications (145)


Co-regulation of Epidermal Permeability Barrier Function and Immune Function: A Narrative Review
  • Article

December 2024

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3 Reads

International Journal of Dermatology and Venereology

Mao-Qiang Man

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Jie-Fang Gao

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Guo-Qiang Zhang

The epidermal permeability barrier, primarily located in the stratum corneum, is largely determined by keratinocyte function in the epidermis. Various internal and external factors can directly or indirectly influence keratinocyte function, leading to changes in epidermal permeability barrier function. Among internal factors, cytokines and immune cells can both positively and negatively regulate this barrier. Conversely, epidermal permeability barrier function also influences cytokine expression and immune cell activity. Studies show that increased IL-1α expression or topical application of IL-6 and TNF-α accelerates epidermal permeability barrier repair in acutely disrupted skin. Additionally, mast cells and Toll-like receptor 2 are essential for formation of the epidermal permeability barrier. However, IL-4, IL-22, and histamine impair its function. Disruption of the epidermal permeability barrier further amplifies cytokine expression, T-cell maturation, and inflammatory cell infiltration in the skin. Thus, epidermal permeability barrier function and immune function co-regulate each other, with proper management of one benefiting the other. This review briefly summarizes the evidence for this co-regulation and its clinical significance.



Correlation of HbA1c with epidermal biophysical properties. (A) Correlation of HbA1c with epidermal biophysical properties (N = 416). (B) Comparison of epidermal biophysical properties in individuals with HbA1c levels < 5.7% versus ≥6.5%. N = 92 for individuals with HbA1c ≥ 6.5%; N = 202 for individuals with HbA1c < 5.7%. Significances are indicated in the figures.
Stratum corneum hydration levels are negatively correlated with HbA1c levels in the elderly Chinese
  • Article
  • Full-text available

October 2024

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13 Reads

Highlights Stratum corneum hydration levels are negatively correlated with HbA1c levels and positively correlated with skin surface pH. Individuals with type 2 diabetes display lower levels of stratum corneum hydration. Because low stratum corneum hydration levels can increase circulating levels of proinflammatory cytokines, which are linked to the pathogenesis of type 2 diabetes, improvement in stratum corneum hydration can be an alternative approach in the management of type 2 diabetes. image

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Interplay between diabetes mellitus and atopic dermatitis

June 2024

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19 Reads

Experimental Dermatology

Inflammatory dermatoses such as atopic dermatitis (AD) have long been linked to the pathogenesis of diabetes mellitus. Indeed, numerous studies show an increased risk of diabetes mellitus in individuals with AD although lower prevalence of diabetes mellitus is also observed in few studies. Though the underlying mechanisms accounting for the reciprocal influence between these two conditions are still unclear, the complex interplay between diabetes mellitus and AD is attributable, in part, to genetic and environmental factors, cytokines, epidermal dysfunction, as well as drugs used for the treatment of AD. Proper management of one condition can mitigate the other condition. In this review, we summarize the evidence of the interaction between diabetes mellitus and AD, and discuss the possible underlying mechanisms by which these two conditions influence each other.


Immunofluorescence and electron microscopy of tissues. (A) Membranes and nuclei were stained with anti‐CLDN5 (green) and Hoechst (blue) in sensitive and normal skin, respectively. Scale bar = 50 nm. (B) Transmission electron microscopy. The TJ structure is shown in red arrows.
CLDN5 downregulation impairs diffusion barrier function. (A) Relative CLDN5 expression levels after siRNA transfection. Data were normalized to NC (transfected with siRNA‐NC), set as 1 and shown in a dotted line. P‐values are versus normal controls (n = 3 for all). (B) CLDN5 knockdown decreased TEER in KCs, compared to the NCs. Data were normalized to the NCs, set as 100% and shown in a dotted line. One‐way ANOVA was applied to assess the differences among groups. P‐values are versus normal controls (n = 3 for all). (C) Lucifer yellow fluorescence (green) was visualized in sections of organotypic skin cultures treated with either CLDN5 siRNA or siRNA‐NC.
MiR‐224‐5p expression in sensitive and normal skin. (A) Volcano plots of DE transcripts. The differences in miRNA expression profiles can be noted in the overall distribution of the transcripts. The red points in the plot represent upregulated transcripts, and the green points represent downregulated transcripts. The default filter threshold is P < 0.05. (B) Hierarchical heat maps of the differentially expressed profiles in sensitive and normal skin. MiRNAs were used to analyze the gene expression data, where the cluster analysis arranged samples into groups according to their expression levels. Each column represents a sample, and each row represents a transcript. “Red” indicates higher expression, and “blue” indicates lower expression. SS, sensitive skin; N, normal skin. (C) Relative expression analysis of CLDN5 and miR‐224‐5p in sensitive and normal skin, as determined using qRT‐PCR (n = 10 for all).
Effects of miR‐224‐5p on the 3`UTR of CLDN5. (A) MiR‐224 binding with the CLDN5 3`UTR region, and design of the 3`UTR CLDN5 mutant site. (B) Relative luciferase activity of CLDN5 wild type or mutant 3`UTR in KCs following transfection with the miR‐224‐5p mimic. One‐way ANOVA was used to determine significant differences. P‐values versus normal controls. (C) CLDN5 protein expression levels. Unpaired t‐test with Welch's correction was used to determine significant differences. P‐values are versus normal controls (n = 3 for all). (D) Western blotting shows changes in CLDN5 expression following treatment with the miR‐224‐5p mimic and miR‐224‐5p inhibitor (n = 3 for all).
Comparisons of CLDN5 protein expression and TEER in the KCs among groups 48 h after transfection. (A) CLDN5 protein expression. (B) TEER. *P < 0.05. (n = 3 for all).
MiRNA‐224‐5p regulates the defective permeability barrier in sensitive skin by targeting claudin‐5

May 2024

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36 Reads

Background Sensitive skin is hypersensitive to various external stimuli and a defective epidermal permeability barrier is an important clinical feature of sensitive skin. Claudin‐5 (CLDN5) expression levels decrease in sensitive skin. This study aimed to explore the impact of CLDN5 deficiency on the permeability barrier in sensitive skin and the regulatory role of miRNAs in CLDN5 expression. Materials and methods A total of 26 patients were retrospectively enrolled, and the CLDN5 expression and permeability barrier dysfunction in vitro were assessed. Then miRNA‐224‐5p expression was also assessed in sensitive skin. Results Immunofluorescence and electron microscopy revealed reduced CLDN5 expression, increased miR‐224‐5p expression, and disrupted intercellular junctions in sensitive skin. CLDN5 knockdown was associated with lower transepithelial electrical resistance (TEER) and Lucifer yellow penetration in keratinocytes and organotypic skin models. The RNA‐seq and qRT‐PCR results indicated elevated miR‐224‐5p expression in sensitive skin; MiR‐224‐5p directly interacted with the 3`UTR of CLDN5, resulting in CLDN5 deficiency in the luciferase reporter assay. Finally, miR‐224‐5p reduced TEER in keratinocyte cultures. Conclusion These results suggest that the miR‐224‐5p‐induced reduction in CLDN5 expression leads to impaired permeability barrier function, and that miR‐224‐5p could be a potential therapeutic target for sensitive skin.



Preventive and Therapeutic Benefits of Natural Ingredients in Photo-Induced Epidermal Dysfunction

April 2024

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10 Reads

Skin Pharmacology and Physiology

Background: The skin, particularly the epidermis, is subjected to various external stresses, including ultraviolet [UV] irradiation. UV irradiation, mainly UVB at wavelength of 280-315 nm, can alter several epidermal functions, including cutaneous inflammation, epidermal hyperproliferation, DNA damage, disruption of epidermal permeability barrier and reduction in stratum corneum hydration levels. Because of the negative impacts of UVB irradiation on epidermal functions, great efforts have been made to develop regimens for the protection of alterations in epidermal function induced by UV irradiation. Summary: While sunscreen can provide physical barrier to UV light, some natural ingredients can also effectively protect the skin from UVB irradiation-induced damages. Studies have demonstrated that either topical or oral administrations of some natural ingredients attenuate UVB irradiation-induced alterations in the epidermal function. The underlying mechanisms by which natural ingredients improve epidermal functions are attributable to antioxidation, stimulation of keratinocyte differentiation, increases in the content of epidermal natural moisturizers and inhibition of inflammation. Key message: Some natural ingredients exhibit protective and therapeutical benefits in photo-induced epidermal dysfunctions via divergent mechanisms.


Benefits of topical natural ingredients on epidermal permeability barrier and clinical applications.
Continued) Topical natural ingredients that benefit epidermal permeability barrier.
Benefits of topical natural ingredients in epidermal permeability barrier

January 2024

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58 Reads

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1 Citation

Because of the crucial role of epidermal permeability barrier in regulation of cutaneous and extracutaneous functions, great efforts have been made to identify and develop the regimens that can improve epidermal permeability barrier function. Studies have demonstrated that oral administration of natural ingredients can improve epidermal permeability barrier in various skin conditions, including inflammatory dermatoses and UV-irradiation. Moreover, topical applications of some natural ingredients can also accelerate the repair of epidermal permeability barrier after acute barrier disruption and lower transepidermal water loss in the intact skin. Natural ingredient-induced improvements in epidermal permeability barrier function can be attributable to upregulation of keratinocyte differentiation, lipid production, antioxidant, hyaluronic acid production, expression of aquaporin 3 and sodium-hydrogen exchanger 1. In this review, we summarize the benefits of topical natural ingredients in epidermal permeability barrier in normal skin with or without acute barrier disruption and the underlying mechanisms.


Aging in the dermis: Fibroblast senescence and its significance

December 2023

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52 Reads

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33 Citations

Skin aging is characterized by changes in its structural, cellular, and molecular components in both the epidermis and dermis. Dermal aging is distinguished by reduced dermal thickness, increased wrinkles, and a sagging appearance. Due to intrinsic or extrinsic factors, accumulation of excessive reactive oxygen species (ROS) triggers a series of aging events, including imbalanced extracellular matrix (ECM) homeostasis, accumulation of senescent fibroblasts, loss of cell identity, and chronic inflammation mediated by senescence‐associated secretory phenotype (SASP). These events are regulated by signaling pathways, such as nuclear factor erythroid 2‐related factor 2 (Nrf2), mechanistic target of rapamycin (mTOR), transforming growth factor beta (TGF‐β), and insulin‐like growth factor 1 (IGF‐1). Senescent fibroblasts can induce and accelerate age‐related dysfunction of other skin cells and may even cause systemic inflammation. In this review, we summarize the role of dermal fibroblasts in cutaneous aging and inflammation. Moreover, the underlying mechanisms by which dermal fibroblasts influence cutaneous aging and inflammation are also discussed.


Figure 1 Schematic diagram: link between cutaneous conditions and aging-associated disorders in the elderly. Aged humans exhibit epidermal dysfunction. Both epidermal dysfunction and inflammatory dermatoses can provoke cutaneous inflammation. Prolonged cutaneous inflammation can result in inflammaging, leading to the development of inflammaging-associated disorders in the elderly (indicated in solid arrows). Conversely, either appropriate treatment of inflammatory dermatoses or improvement in epidermal function can decrease cutaneous inflammation, preventing the development and progression of inflammaging, consequently alleviating inflammaging-associated disorders in the elderly (indicated in dotted arrows). Abbreviation: PAR2, protease-activated receptor 2.
Improvement in Cutaneous Conditions Can Benefit Some Health Conditions in the Elderly

December 2023

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43 Reads

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2 Citations

As we are aging, a number of cutaneous and extracutaneous disorders will be developed. Although the pathogenesis of these aging-associated disorders is not clear yet, abnormalities in the skin are linked to some aging-associated disorders at least to some extent. Inflammatory dermatoses such as psoriasis and atopic dermatitis predispose to the development of cardiovascular diseases, obesity and type 2 diabetes. In addition, both chronologically aged skin and individuals with some aging-associated systemic conditions display altered epidermal function, such as reduced stratum corneum hydration levels, which can provoke cutaneous inflammation. Because aged skin exhibits higher expression levels of inflammatory cytokines, which play a pathogenic role in a variety of aging-associated health condition, the association of the skin with some aging-associated disorders is likely mediated by inflammation. This postulation is supported by the evidence that improvement in either epidermal function or inflammatory dermatoses can mitigate some aging-associated disorders such as mild cognitive impairment and insulin sensitivity. This perspective discusses the association of the skin with aging-associated disorders and highlights the potential of improvement in cutaneous conditions in the management of some health conditions in the elderly.


Citations (79)


... Either reduced SCH or increased stratum corneum pH increases cutaneous inflammation, while cutaneous inflammation can provoke systemic inflammation. 10 SCH levels negatively correlate with circulating levels of proinflammatory cytokines in the elderly.10 Although serum cytokines were not measured in this study, previous study showed that improvements in epidermal functions with topical emollient significantly lower serum levels of proinflammatory cytokines in both humans and mice.11,12 ...

Reference:

Epidermal functions are associated with constipation in the elderly
Improvement in Cutaneous Conditions Can Benefit Some Health Conditions in the Elderly

... It was highly statistically significant compared to the controls (7.2%) (p < 0.0001). This finding is in line with recent studies that showed children with ASD exhibited an increased transepidermal water loss rate (TEWL) due to dry skin and epidermal dysfunction [31,32]. This finding could be attributed to the effects of multiple factors, including climatic factors, poor skincare routines, and the nature of the skin itself. ...

Link between the skin and autism spectrum disorder

... Furthermore, central adiposity can induce oxidative stress, which accelerates the degradation of collagen and elastin in the skin, leading to premature aging, as demonstrated by the accumulation of creases (Papaccio et al., 2022;Zhu et al., 2023). ...

Association of Epidermal Biophysical Properties with Obesity and Its Implications
  • Citing Article
  • August 2023

Skin Pharmacology and Physiology

... This case suggests that dupilumab has been used safely in a patient with pemphigus vulgaris complicated by TB. Furthermore, a study by Yuan et al. indicated that using prophylaxis therapy (anti-TB therapy) while administering biologic treatments (adalimumab, secukinumab, guselkumab) for psoriatic patients with latent TB infection significantly reduced TB reactivation by 14% and decreased adverse events associated with biologic treatment [5]. To our knowledge, our case is unique as it is the first reported instance of using dupilumab for bronchial asthma with concomitant pulmonary TB. ...

Safety of Biologics for Psoriatic Patients with Latent Tuberculosis

... With the COVID-19 pandemic, several studies and case reports have reported the worsening of Psoriasis patients' conditions and suggested an association between Psoriasis exacerbation and SARS-CoV-2 infection, indicating that the virus can induce the worsening of this disease [31][32][33][34]. Epidemiological data regarding the incidence of this phenomenon is not fully developed yet; however, research shows that both Psoriasis and COVID-19 are capable of negatively influencing each other's outcomes, meaning that Psoriasis patients infected by the virus tend to develop both a severe SARS-CoV-2 infection and a worsening of Psoriasis [35,36]. ...

Psoriasis and COVID-19 Infection Negatively Impact Each Other: An Analysis of 3581 Cases

... Malassezia hyperproliferation is a known contributor to SD, an inflammatory skin disease [65]. Compared to normal skin, SD tended to exhibit increased TEWL [66]. Similarly, scalps with SD showed increased TEWL and decreased hydration compared to normal scalps [65]. ...

Rosacea and seborrheic dermatitis differentially respond to lactic acid sting and capsaicin tests in Chinese women
  • Citing Article
  • July 2023

... These signaling molecules then activate macrophages and T cells, further promoting inflammation. The resulting inflammatory state can further elevate leptin levels, which can create a vicious cycle by further suppressing adiponectin and PPARg (13). The leptin secreted in obese or overweight individuals can upregulate the expression levels of cytokines and chemokines, thereby increase the risk of AD. ...

Link between obesity and atopic dermatitis: Does obesity predispose to atopic dermatitis, or vice versa?
  • Citing Article
  • April 2023

Experimental Dermatology

... It was highly statistically significant compared to the controls (7.2%) (p < 0.0001). This finding is in line with recent studies that showed children with ASD exhibited an increased transepidermal water loss rate (TEWL) due to dry skin and epidermal dysfunction [31,32]. This finding could be attributed to the effects of multiple factors, including climatic factors, poor skincare routines, and the nature of the skin itself. ...

Alterations in Epidermal Biophysical Properties in Autistic Children
  • Citing Article
  • March 2023

Skin Pharmacology and Physiology

... The skin is among the organs most frequently affected by diabetes complications. High blood glucose levels lead to dehydration and dysfunction of sweat glands, resulting in decreased epidermal hydration [23]. Xerosis can affect any area of the skin and is characterized by flaking and scaling, often associated with advanced disease [24]. ...

Alterations in epidermal function in type 2 diabetes: Implications for the management of this disease