Involvement of DKK1 secreted from adipose-derived stem cells in alopecia areata.

Adipose-derived stem cells (ASCs) have shown efficacy in promoting hair growth, while DKK1 inhibits the WNT pathway, which is associated with hair loss. Our study focused on investigating the expression of DKK1 in alopecia areata (AA), a condition characterised by significant increases in the DKK1 levels in human and mouse ASCs. Treatment of interferon-γ increased the expression of DKK1 via STAT3 phosphorylation in ASCs. Treatment with recombinant DKK1 resulted in a decrease of cell growth in outer root sheath cells, whereas the use of a DKK1 neutralising antibody promoted hair growth. These results indicate that ASCs secrete DKK1, playing a crucial role in the progression and development of AA. Consequently, we generated DKK1 knockout (KO) ASCs using the Crispr/Cas9 system and evaluated their hair growth-promoting effects in an AA model. The DKK1 KO in ASCs led to enhanced cell motility and reduced cellular senescence by activating the WNT signalling pathway, while it reduced the expression of inflammatory cytokines by inactivating the NF-kB pathway. As expected, the intravenous injection of DKK1-KO-ASCs in AA mice, and the treatment with a conditioned medium derived from DKK1-KO-ASCs in hair organ culture proved to be more effective compared with the use of naïve ASCs and their conditioned medium. Overall, these findings suggest that DKK1 represents a novel therapeutic target for treating AA, and cell therapy using DKK1-KO-ASCs demonstrates greater efficiency.

Is colorectal endoscopic submucosal dissection safe and effective for 15-19-mm tumors?

PURPOSE: The outcomes of colorectal endoscopic submucosal dissection (ESD) in 15-19-mm tumors are unclear. This study compared the effectiveness and safety of colorectal ESD for 15-19-mm tumors and tumors exceeding that size. METHODS: From August 2018 to December 2020, 213 cases of colorectal tumors removed by colorectal ESD at a tertiary hospital were enrolled in this study. The cases were divided into two groups according to the pathologically measured size of the resected lesion: an intermediate group (15-19 mm, n = 62) and a large group (≥ 20 mm, n = 151). The en bloc resection rate, complete resection rate, and complications were investigated retrospectively. RESULTS: The en bloc resection rate was significantly higher in the intermediate than large group (100% vs. 94%, p = 0.049), and the mean total procedure time was shorter in the intermediate than large group (29.2 [Formula: see text] 12.6 vs. 48.4 [Formula: see text] 28.8 min, p < 0.001). However, the mean procedure speed was significantly lower in the intermediate than large group (0.25 [Formula: see text] 0.10 vs. 0.28 [Formula: see text] 0.11 cm2/min, p = 0.031). The complete resection rate, post-procedural bleeding, and perforation rate were not significantly different between the two groups. In multivariate analyses, the total procedure time and mean procedure speed were significantly associated with lesion size. CONCLUSION: Colorectal ESD of 15-19-mm lesions is effective, and has a shorter procedure time and higher en bloc resection rate than the same procedure for larger lesions.

CXCL12 inhibits hair growth through CXCR4.

CXCL12 and its receptors, which are highly expressed in the skin, are associated with various cutaneous diseases, including androgenic alopecia. However, their expression and role during the hair cycle are unknown. This study aims to investigate the expression of CXCL12 and its receptor, CXCR4, in the vicinity of hair follicles and their effect on hair growth. CXCL12 was highly expressed in dermal fibroblasts (DFs) and its level was elevated throughout the catagen and telogen phases of the hair cycle. CXCR4 is expressed in the dermal papilla (DP) and outer root sheath (ORS). In hair organ culture, hair loss was induced by recombinant CXCL12 therapy, which delayed the telogen-to-anagen transition and decreased hair length. In contrast, the suppression of CXCL12 using a neutralizing antibody and siRNA triggered the telogen-to-anagen transition and increased hair length in hair organ culture. Neutralization of CXCR7, one of the two receptors for CXCL12, only slightly affected hair growth. However, inhibition of CXCR4, the other receptor for CXCL12, increased hair growth to a considerable extent. In addition, in hair organ culture, the conditioned medium from DFs with CXCL12 siRNA considerably increased the hair length and induced proliferation of DP and ORS cells. CXCL12, through CXCR4 activation, increased STAT3 and STAT5 phosphorylation in DP and ORS cells. In contrast, blocking CXCL12 and CXCR4 decreased the phosphorylation of STAT3 and STAT5. In summary, these findings suggest that CXCL12 inhibits hair growth via the CXCR4/STAT signaling pathway and that CXCL12/CXCR4 pathway inhibitors are a promising treatment option for hair growth.

Non-thermal atmospheric pressure plasma activates Wnt/ß-catenin signaling in dermal papilla cells.

There is an unmet need for novel, non-pharmacological therapeutics to treat alopecia. Recent studies have shown the potential biological benefits of non-thermal atmospheric pressure plasma (NTAPP), including wound healing, angiogenesis, and the proliferation of stem cells. We hypothesized that NTAPP might have a stimulatory effect on hair growth or regeneration. We designed an NTAPP-generating apparatus which is applicable to in vitro and in vivo experiments. The human dermal papilla (DP) cells, isolated fresh hair follicles, and mouse back skin were exposed with the NTAPP. Biological outcomes were measured using RNA-sequencing, RT-PCR, Western blots, and immunostaining. The NTAPP treatment increased the expression levels of Wnt/ß-catenin pathway-related genes (AMER3, CCND1, LEF1, and LRG1) and proteins (ß-catenin, p-GSK3ß, and cyclin D1) in human DP cells. In contrast, inhibitors of Wnt/ß-catenin signaling, endo-IWR1 and IWP2, attenuated the levels of cyclin D1, p-GSK3ß, and ß-catenin proteins induced by NTAPP. Furthermore, we observed that NTAPP induced the activation of ß-catenin in DP cells of hair follicles and the mRNA levels of target genes of the ß-catenin signaling pathway (CCND1, LEF1, and TCF4). NTAPP-treated mice exhibited markedly increased anagen induction, hair growth, and the protein levels of ß-catenin, p-GSK3ß, p-AKT, and cyclin D1. NTAPP stimulates hair growth via activation of the Wnt/ß-catenin signaling pathway in DP cells. These findings collectively suggest that NTAPP may be a potentially safe and non-pharmacological therapeutic intervention for alopecia.

Genome-Wide Transcriptome Analysis of Rice Seedlings after Seed Dressing with Paenibacillus yonginensis DCY84T and Silicon.

Plant-growth-promoting bacteria (PGPB) are beneficial microorganisms that can also protect against disease and environmental stress. Silicon (Si) is the second most abundant element in soil, and is known to increase plant growth, grain yield, resistance to biotic stress, and tolerance to abiotic stress. Combined treatment of PGPB and Si has been shown to further enhance plant growth and crop yield. To determine the global effects of the PGPB and Si on rice growth, we compared rice plants treated with Paenibacillus yonginensis DCY84T (DCY84T) and Si with untreated rice. To identify the genes that respond to DCY84T+Si treatment in rice, we performed an RNA-Seq transcriptome analysis by sampling treated and untreated roots on a weekly basis for three weeks. Overall, 576 genes were upregulated, and 394 genes were downregulated in treated roots, using threshold fold-changes of at least 2 (log2) and p-values < 0.05. Gene ontology analysis showed that phenylpropanoids and the L-phenylalanine metabolic process were prominent in the upregulated genes. In a metabolic overview analysis using the MapMan toolkit, pathways involving phenylpropanoids and ethylene were strongly associated with upregulated genes. The functions of seven upregulated genes were identified as being associated with drought stress through a literature search, and a stress experiment confirmed that plants treated with DCY84T+Si exhibited greater drought tolerance than the untreated control plants. Furthermore, the predicted protein-protein interaction network analysis associated with DCY84T+ Si suggests mechanisms underlying growth promotion and stress tolerance.

HMGB1 promotes hair growth via the modulation of prostaglandin metabolism.

Unexpected hair growth can occur after tissue injury. The pathogenic mechanism for this phenomenon is unknown but is likely related to inflammatory mediators. One such mediator is high-mobility group box 1 (HMGB1), a ubiquitous nuclear protein that is released from cell nuclei after tissue damage. To elucidate the effect of HMGB1 on hair growth and understand its mechanism of action, we evaluated the effect of HMGB1 treatment on hair shaft elongation and on mRNA and protein expression in cultured human dermal papilla cells (hDPCs). HMGB1 enhanced hair shaft elongation in an ex vivo hair organ culture. In hDPCs, HMGB1 treatment significantly increased mRNA and protein expression levels of prostagladin E synthases. HMGB1 also stimulated prostaglandin E2 (PGE2) secretion from hDPCs. Finally, blocking the receptor for advanced glycation end-products, a canonical HMGB1 receptor, inhibited HMGB1-induced PGE2 production and hair shaft elongation. Our results suggest that HMGB1 promotes hair growth via PGE2 secretion from hDPCs. This mechanism can explain the paradoxical phenomenon of trauma-induced hair growth. Thus, HGMB1 can be a viable therapeutic target for the treatment of alopecia.

Combining Follicular Unit Extraction and Scalp Micropigmentation for the Cosmetic Treatment of Alopecias.

Two relatively new modalities, follicular unit extraction (FUE) and scalp micropigmentation have changed the treatment of hair loss, to reduce the number of procedures and the total costs of the hair restoration process. These 2 modalities augment each other when treating patients with thinning hair and balding. The explosion of FUE procedures (which reflected 52.6% of the hair transplant procedures performed in 2016, up from 48.5%) and the appearance of more and more new physicians offering hair restoration technologies employing FUE have caused a 20% annual growth in this industry over the past few years. This article reviews the use of FUE and scalp micropigmentation when used in combination.

Scalp micropigmentation: a concealer for hair and scalp deformities.

BACKGROUND: Cosmetic deformities, resulting from some dermatologic diseases or deformities caused by hair restoration surgeries, have had few, if any, good, permanent solutions. Most of these patients have learned to live with their problems. OBJECTIVE: A cosmetic tattoo technique has been developed to address unsightly scalp and hair conditions. MATERIALS AND METHODS: The technique called scalp micropigmentation uses specialized techniques and conventional cosmetic tattoo instruments and pigments in a stippling pattern on the scalp. RESULTS: A variety of alopecias, refractory to treatment and hair transplant deformities, impact millions of men and women. Many of these deformities can be concealed with scalp micropigmentation, making the deformities minimally detectable. Included are the results of treatment. Patient satisfaction is very high. CONCLUSION: Scalp micropigmentation offers a good nonsurgical alternative treatment for hair and scalp deformities. This paper demonstrates scalp micropigmentation results and discusses the histology, physiology, and pathology of tattoo pigments in the skin. The regulation of the tattoo process by the United States Food and Drug Administration and state governments is summarized. Unlike medical devices, scalp micropigmentation offers a tattoo-based, non-medical "cover-up" that effectively hides unsightly conditions on the scalp and creates the illusion of thicker hair. The authors believe that scalp micropigmentation is destined to become a standardized offering for physicians specializing in cosmetic office procedures.

Phenotype of normal hairline maturation.

Hairlines change shape with age, starting at birth. A good head of hair is frequently present some time after ages 3 to 5 years. The look of childhood has its corresponding hairline, and, as the child grows and develops into adulthood, facial morphology migrate changes from a childlike look to a more mature look. This article discusses the dynamics of hairline evolution and the phenotypic variations of the front and side hairlines in men and women. A modeling system is introduced that provides a common language to define the various anatomic points of the full range of hairlines.

Scalp micropigmentation: a useful treatment for hair loss.

Scalp micropigmentation (SMP) is a highly sophisticated medical tattoo process for balding or thinning hair. SMP looks amazingly simple, but this novel technique must be customized for each patient because the skin in each patient differs with regard to how the scalp reacts as it holds on to the tattoo dye. There are many variables involved with performing SMP that makes this process more of an art form than a science. SMP is a very labor-intensive process that could require multiple sessions and up to 20 hours of procedural time to satisfy the patient. This review discusses applications and technical considerations of the SMP process.

Three-dimensional assessment of zygomatic malunion using computed tomography in patients with cheek ptosis caused by reduction malarplasty.

BACKGROUND: Reduction malarplasty is one of the most popular aesthetic surgical procedures for reshaping facial contour in oriental people. Especially for those who have a wide midface and a prominent zygoma. Although malunion and cheek ptosis are known as major complications in reduction malarplasty, but there have been few reports about their causes and patterns. The authors experienced many revision reduction malarplasty using the coronal approach to correct cheek ptosis with malunion and were able to categorize the types of malunion by analyzing 3-dimensional CT imaging prior to revision surgery. METHODS: A total of 24 patients underwent revision reduction malarplasty with the coronal approach to correct the unfavorable result after primary malarplasty. Most patients complained of various degrees of cheek ptosis associated with malunion. In all cases, the status of zygomatic malunion was evaluated through 3D CT imaging. The operative procedures during revision surgery including repositioning of the inferolaterally displaced malar complex to the appropriate position and obtaining bone-to-bone contact with rigid fixation. If bony absorption at non-union margin was found during the operation, bihalved calvarial bone was grafted into the bony gap. Midface and forehead lifts were also performed when indicated. RESULTS: The types of zygomatic malunion could be categorized into four patterns according to the shape of displacement. The degree of displacement was relevant to the condition of the fixation in all cases. The higher the grade of malunion was evaluated in 3D CT imaging, the more difficult procedures it required during revision surgery. The postoperative results in all cases were satisfactory without any complications. CONCLUSIONS: In reduction malarplasty, inappropriate fixation and the ignorance of repositioning vector can lead to cheek ptosis and malunion by the action of masseter muscle. The malunion types apprehended by the preoperative 3D CT scanning enabled precise operative planning before revision surgery. In all grades of zygomatic malunion with cheek ptosis, revision reduction malarplasty with coronal approach was a very useful solution because it offers a wide surgical field, enables accurate repositioning along with firm fixation and easily allows simultaneous midface lift.

Influence of operation conditions and additives on the development of producer gas and tar reduction in air gasification of construction woody wastes using a two-stage gasifier.

Air gasification was conducted with fractions of construction woody wastes in a two-stage gasifier, consisting of a fluidized bed zone and a tar cracking zone. The aim of this work is to investigate the influence of reaction conditions and additives on the composition of producer gas and tar content in producer gas. A producer gas obtained with activated carbon of 540 g at an ER of 0.26 was mainly composed of H(2) (25 vol.%), CO (22 vol.%) and CH(4) (5 vol.%). Regarding tar removal efficiency, activated carbon was better than olivine. The tar removal rate with virgin activated carbon reached up to 80%. The reuse of spent activated carbon caused an efficiency loss in tar removal to some extent. Overall, it seems that the strong need for intensive downstream tar removal measurements can be removed with the use of a two-stage gasifier and the application of activated carbon.

Revision reduction malarplasty with coronal approach.

BACKGROUND: Although reduction malarplasty is one of the most popular aesthetic surgical procedures in Asia, there have been a few reports of complications or unfavourable results. A poor understanding of the repositioning vector of the malar segment or improper fixation can result in unsatisfactory outcomes, such as non-union or inferolaterally displaced malunion of the malar complex. The authors present some revision malarplasty cases of patients with unfavourable or complicated outcomes to emphasise the importance of accurate repositioning and firm fixation of the malar complex in reduction malarplasty. METHODS: A total of 20 patients underwent revision malarplasty by the coronal approach after an unfavourable primary reduction malarplasty. The major complaints included cheek drooping, depression, asymmetry and overcorrection. After repositioning the inferolaterally displaced malar complex to the appropriate position and obtaining bone-to-bone contact, rigid fixation was performed with a plate and screw. The calvarian bone was grafted to the bony gap. Midface and forehead lifts were also performed when indicated. RESULTS: Most patients had satisfactory results without severe complications. Two patients required a secondary revision due to asymmetry and non-union. Three patients developed frontal palsies, which were all temporary. CONCLUSION: Precise repositioning of the malar complex and firm fixation are essential for reduction malarplasty. The coronal approach is recommended when encountering unfavourable results or complications because it offers a wide surgical field for repositioning and fixation of the malar complex.