Through a comprehensive analysis combining network pharmacology prediction and transcriptomics, this study systematically explained the multi-target mechanism of Cyanotis arachnoidea(CA) Gel in improving melasma. A melasma model was induced in female SD rats by progesterone injection combined with ultraviolet B(UVB) irradiation for 40 consecutive days, while the blank control group was only fed routinely. After successful model establishment, the rats were randomly divided into five groups and administered different doses of CA ethanol extract gel(high, medium, and low doses) or arbutin Gel(positive control), which were applied once daily for 28 consecutive days. Subsequently, the levels of superoxide dismutase(SOD), malondialdehyde(MDA), and tyrosinase(TYR) in the skin, serum, and liver tissues were measured. Hematoxylin-eosin(HE) staining and Masson-Fontana staining were used to observe the pathological changes in the tissues. Network pharmacology combined with transcriptomics was employed to identify core targets and pathways, and the differential gene expression was validated by quantitative real-time PCR(qPCR). Pharmacodynamic experiments showed that CA Gel significantly increased SOD activity and decreased MDA and TYR levels in the skin, serum, and liver of model rats. It also improved epidermal thickening, inflammatory infiltration, collagen loss, and melanin deposition. Network pharmacology analysis showed that CA mainly regulated core targets such as signal transducer and activator of transcription 3(STAT3), epidermal growth factor receptor(EGFR), and interleukin-6(IL-6), and modulated the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(AKT) and interleukin-17(IL-17) signaling pathways. Transcriptomic analysis showed that CA Gel significantly downregulated the gene expression of heat shock protein 90β family member 1(Hsp90b1), heat shock protein 90α family member 1(Hsp90aa1), and the key steroid synthesis enzyme cytochrome P450 family 17 subfamily A member 1(Cyp17a1), while upregulating thioredoxin 1(Txn1). qPCR results confirmed that CA Gel regulated oxidative stress and inflammatory response by inhibiting the IL-17 signaling pathway and steroid hormone synthesis. This study, for the first time, reveals the molecular mechanism of CA Gel in improving melasma through multi-target synergistic regulation of oxidative stress, inflammatory response, and hormone metabolism pathways, providing a scientific basis for the treatment of pigmentation diseases with traditional Chinese medicine.
Animals ; Rats ; Female ; Rats, Sprague-Dawley ; Network Pharmacology ; Drugs, Chinese Herbal/administration & dosage* ; Melanosis/metabolism* ; Transcriptome/drug effects* ; Humans ; Superoxide Dismutase/genetics* ; Signal Transduction/drug effects* ; Malondialdehyde/metabolism*

OBJECTIVETo study the clinicopathologic features and differential diagnosis of cutaneous regressing/regressed melanoma.

METHODSHistopathologic evaluation and immunohistochemical study by EnVision method were performed in 8 cases of cutaneous regressing/regressed melanoma. The clinical presentation, treatment and follow-up data were analyzed.

RESULTSThe age of the patients ranged from 40 to 69 years (mean 58 years). The male-to-female ratio was 3: 1. Tumors were located on the back (4 cases), sole of the foot (2 cases), ventral aspect of the toes (1 case), and the forearm (1 case). Clinically, 6 patients presented with progressive black mole of the skin, followed by subsequent focal hypopigmentation, even scarring. Two patients presented with multiple foci of dark-brown pigmentation. Microscopically, 3 cases were completely regressed malignant melanoma. Tumoral melanosis was found in 1 of 3 cases. The other 5 cases were melanoma with severe regression. The extent of regression ranged from 75% to 90%. The Breslow depth of the tumors ranged from 0.5 to 1.0 mm. Immunohistochemically, both metastatic and primary tumor cells were diffusely positive for S-100, HMB45 and Melan A, while melanophages were positive for CD68. Follow-up data were available in 8 patients, ranging from 8 to 27 months. Five patients were alive with no evidence of disease, 1 patient was alive with stable disease and 2 patients died of metastatic melanoma.

CONCLUSIONSCorrelation between clinical presentation and pathologic features is important for diagnosis of cutaneous regressing/regressed melanoma. Thin melanoma with extensive regression ( ≥ 75%) should not been regarded as low metastatic risk and wide excision combined with sentinel lymph node biopsy is recommended.

Adult ; Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Back ; pathology ; Female ; Follow-Up Studies ; Foot ; pathology ; Humans ; Lymphatic Metastasis ; MART-1 Antigen ; metabolism ; Male ; Melanoma ; metabolism ; pathology ; surgery ; Melanoma-Specific Antigens ; metabolism ; Melanosis ; pathology ; Middle Aged ; S100 Proteins ; metabolism ; Sentinel Lymph Node Biopsy ; Skin Neoplasms ; metabolism ; pathology ; surgery ; Toes ; pathology ; Treatment Outcome

OBJECTIVETo observe the efficacy difference between meridian cosmetology and western medicine in the treatment of chloasma and explore the impacts of meridian cosmetology on E2 and PRGE.

METHODSThree hundreds cases of chloasma were randomized into a meridian cosmetology group and a western medication group according to the visit sequence, 150 cases in each one. In the meridian cosmetology group, the meridian regulation, acupuncture based on pattern/syndrome differentiation [at the body acupoints such as Qihai (CV 6), Xuehai (SP 10), Zusanli (ST 36), Sanyinjiao (SP 6), Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23), etc.] and the local surrounding needling therapy on the chloasma skin lesion were adopted. In the western medication group, the oral administration of Vitamin C and E was prescribed for 3 months. The clinical efficacy was observed for the patients in the two groups. Additionally, 30 cases were collected from the meridian cosmetology group randomly for the detection of estrogen (E2) and progestin (PRGE) before and after treatment.

RESULTSThe effective rate in the meridian cosmetology group was 92.6% (126/136), which was superior to 67.0% (75/112) in the western medication group (P < 0.05). For the patients collected from the meridian cosmetology group, as compared with that before treatment, E2 level was decreased (P < 0.01) and PRGE level was increased (P < 0.05).

CONCLUSIONThe meridian cosmetology achieves the superior efficacy as compared with the western medication group for the chloasma and it can regulate the levels of E2 and PRGE.

Acupuncture Therapy ; Adult ; Cosmetic Techniques ; Estrogens ; metabolism ; Female ; Humans ; Melanosis ; metabolism ; therapy ; Meridians ; Progestins ; metabolism ; Young Adult

OBJECTIVETo explore the significance of colonic epithelial cell apoptosis and tumor necrosis factor α (TNF-α) changing in pathogenesis of melanosis coli (MC) in guinea pig and the molecular mechanism of rhubarb (Rhu) in inducing the disease, by means of using different dosages of Rhu to induce the disease.

METHODSOne hundred and forty-four male guinea pigs, clean grade, were randomized according to their body weight into 5 groups, the untreated normal group and the 4 Rhu groups treated, respectively, with different doses of Rhu, 3 g/kg·d for low dose (Rhu-l) group, 6 g/kg·d for moderate dose (Rhu-m) group, 12 g/kg·d for high dose (Rhu-h) group and 24 g/kg·d for super-high dose (Rhu-s) group via gastric infusion. All animals were sacrificed 60 days later, their viscera were taken for observing the pathologic and morphologic changes with HE, melanin and melatonin staining, and the apoptosis of colonic epithelial cells was detected with TUNEL stain and transmission electric microscopy. In addition, the levels of TNF-α in serum and colonic tissue were measured using ELISA and RT-PCR.

RESULTSThe pathological changes of MC could be found by naked eye in all Rhu groups, especially apparent at caecum and proximal end of colon, but did not found in gallbladder, jejunum and ileum. In normal guinea pigs, the colonic membrane was pink in color with no apparent pigment deposition. Membranous color deepened in the Rhu groups depending on the dosage of Rhu used. MC scoring showed the highest scores revealed in the Rhu-s group (6.00±0.00), which was significantly different to those in the Rhu-l (3.86±0.69), Rhu-m (4.43±0.79) and Rhu-h groups (4.88±0.35, all P<0.05). Levels of cell apoptosis in colon and TNF-α in serum in all Rhu groups were higher than those in the normal group (P<0.01), but showed no significant difference among the Rhu groups (P>0.05). Moreover, a positive correlation was found in the degree of induced MC with apoptosis rate and TNF-α level.

CONCLUSIONSRhu (anthraquinone purgatives) had apparent effect on inducing MC; its molecular mechanism is maybe to destroy intestinal mucosal barrier and advance proinflammatory factor TNF-α releasing, which leads to colonic epithelial cells apoptosis, and finally induce the change of MC due to the deposition of brown pigments, i.e. the macrophage phagocytized apoptotic body, on the colonic membrane.

Animals ; Anthraquinones ; adverse effects ; Apoptosis ; drug effects ; Cathartics ; adverse effects ; Colon ; pathology ; ultrastructure ; Colonic Diseases ; blood ; chemically induced ; complications ; pathology ; Epithelial Cells ; drug effects ; pathology ; Gene Expression Regulation ; drug effects ; Guinea Pigs ; In Situ Nick-End Labeling ; Male ; Melanosis ; blood ; chemically induced ; complications ; pathology ; RNA, Messenger ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; blood ; genetics

OBJECTIVETo study the induced change of tumor necrosis factor alpha (TNF-alpha) level in serum and colon tissue of guinea pig model with melanosis coli and its significance induced by rhubarb (RB).

METHODSOne hundred and twelve guinea pigs of clean grade were randomly divided into four groups: the 16 in the normal group (untreated) and the 3 RB groups (32 in each) treated with low (3 g/kg d), medium (6 g/kg d), and high (12 g/kg d) dose of rhubarb respectively, administered by gastrogavage for 60 successive days. All guinea pigs were sacrificed at the terminal of the experiment and their blood serum and colon tissue were taken for detecting TNF-alpha level and TNF-alpha mRNA expression qualitatively and quantitatively using ELISA and RT-PCR.

RESULTSCompared with the normal group, serum and colonic tissue levels of TNF-alpha and TNF-alpha mRNA expression in the RB groups were higher significantly (P<0.01), while no significant difference was found among the later three groups (P>0.05).

CONCLUSIONRB could induce change of TNF-alpha level in serum and colon tissue of guinea pig with melanosis coli.

Animals ; Colonic Diseases ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Female ; Guinea Pigs ; Intestinal Mucosa ; metabolism ; Male ; Melanosis ; metabolism ; Random Allocation ; Rheum ; chemistry ; Tumor Necrosis Factor-alpha ; metabolism

Adult ; Antigens, Neoplasm ; analysis ; Diagnosis, Differential ; Female ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging ; Melanoma ; cerebrospinal fluid ; metabolism ; pathology ; Melanoma-Specific Antigens ; Melanosis ; cerebrospinal fluid ; metabolism ; pathology ; Meningeal Neoplasms ; cerebrospinal fluid ; metabolism ; pathology ; Meninges ; chemistry ; pathology ; Neoplasm Proteins ; analysis ; S100 Proteins ; analysis

Antigens, Neoplasm ; Brain ; metabolism ; pathology ; Humans ; Infant, Newborn ; Lung ; metabolism ; pathology ; Male ; Melanoma-Specific Antigens ; Melanosis ; complications ; congenital ; metabolism ; pathology ; Neoplasm Proteins ; metabolism ; Neurocutaneous Syndromes ; complications ; congenital ; metabolism ; pathology ; S100 Proteins ; metabolism ; Skin ; metabolism ; pathology

We compared the pigment of melanosis coli with the pigment of Dubin-Johnson syndrome, melanin, and lipofuscin. The pigment of melanosis coli appeared similar to lipofuscin in that it stained positively with periodic acid-Schiff, oil red-0 and Victoria blue stains and revealed negative reactions to the immunohistochemical stains for S-100 protein and neuron specific enolase, but had similarity to melanin as shown by the positive reaction to Fontana-Masson stain and negative autofluorescence. The pigment of Dubin-Johnson syndrome showed the same histochemical and immunohistochemical characteristics as that of melanosis coli. The results indicate that the pigments of melanosis coli and Dubin-Johnson syndrome are identical and are variants of lipofuscin.
Case Report ; Colonic Diseases/*metabolism ; Comparative Study ; Histocytochemistry ; Human ; Immunohistochemistry ; Jaundice, Chronic Idiopathic/*metabolism ; Male ; Melanosis/*metabolism ; Middle Age ; Pigments/*metabolism ; Support, Non-U.S. Gov't