Anti-inflammation is an important way that Qingre-Huazhuo-Jiangsuan recipe treats acute gouty arthritis.

Background: Acute gouty arthritis (AGA) significantly impairs patients' quality of life. Currently, existing therapeutic agents exhibit definite efficacy but also lead to serious adverse reactions. Therefore, it is essential to develop highly efficient therapeutic agents with minimal adverse reactions, especially within traditional Chinese medicine (TCM). Additionally, food polyphenols have shown potential in treating various inflammatory diseases. The Qingre-Huazhuo-Jiangsuan-Recipe (QHJR), a modification of Si-Miao-San (SMS), has emerged as a TCM remedy for AGA with no reported side effects. Recent research has also highlighted a strong genetic link to gout. Methods: The TCM System Pharmacology (TCMSP) database was used to collect the main chemical components of QHJR and AGA-related targets for predicting the metabolites in QHJR. HPLC-Q-Orbitrap-MS was employed to identify the ingredients of QHJR. The collected metabolites were then used to construct a Drugs-Targets Network in Cytoscape software, ranked based on their "Degree" of significance. Differentially expressed genes (DEGs) were screened in the Gene Expression Omnibus (GEO) database using GEO2R online analysis. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The DEGs were utilized to construct a Protein-Protein Interaction (PPI) Network via the STRING database. In vivo experimental validation was conducted using colchicine, QHJR, rapamycin (RAPA), and 3-methyladenine (3-MA) as controls to observe QHJR's efficacy in AGA. Synovial tissues from rats were collected, and qRT-PCR and Western blot assays were employed to investigate Ampk-related factors (Ampk, mTOR, ULK1), autophagy-related factors (Atg5, Atg7, LC3, p62), and inflammatory-related factors (NLRP3). ELISA assays were performed to measure inflammatory-related factor levels (IL-6, IL-1ß, TNF-α), and H&E staining was used to examine tissue histology. Results: Network analysis screened out a total of 94 metabolites in QHJR for AGA. HPLC-Q-Orbitrap-MS analysis identified 27 of these metabolites. Notably, five metabolites (Neochlorogenic acid, Caffeic acid, Berberine, Isoliquiritigenin, Formononetin) were not associated with any individual herbal component of QHJR in TCMSP database, while six metabolites (quercetin, luteolin, formononetin, naringenin, taxifolin, diosgenin) overlapped with the predicted results from the previous network analysis. Further network analysis highlighted key components, such as Caffeic acid, cis-resveratrol, Apigenin, and Isoliquiritigenin. Other studies have found that their treatment of AGA is achieved through reducing inflammation, consistent with this study, laying the foundation for the mechanism study of QHJR against AGA. PPI analysis identified TNF, IL-6, and IL-1ß as hub genes. GO and KEGG analyses indicated that anti-inflammation was a key mechanism in AGA treatment. All methods demonstrated that inflammatory expression increased in the Model group but was reversed by QHJR. Additionally, autophagy-related expression increased following QHJR treatment. The study suggested that AMPKα and p-AMPKα1 proteins were insensitive to 3 MA and RAPA, implying that AMPK may not activate autophagy directly but through ULK1 and mTOR. Conclusion: In conclusion, this study confirms the effectiveness of QHJR, a modified formulation of SMS (a classic traditional Chinese medicine prescription for treating gout), against AGA. QHJR, as a TCM formula, offers advantages such as minimal safety concerns and potential long-term use. The study suggests that the mechanism by which QHJR treats AGA may involve the activation of the AMPK/mTOR/ULK1 pathway, thereby regulating autophagy levels, reducing inflammation, and alleviating AGA. These findings provide new therapeutic approaches and ideas for the clinical treatment of AGA.

AGA induces sub-G1 cell cycle arrest and apoptosis in human colon cancer cells through p53-independent/p53-dependent pathway.

BACKGROUND: Despite the advancement in chemotherapeutic drugs for colon cancer treatment, it is still a life-threatening disease worldwide due to drug resistance. Therefore, an urgently needed to develop novel drugs for colon cancer therapies. AGA is a combination of traditional Chinese medicine Antler's extract (A), Ganoderma lucidum (G), and Antrodia camphorata (A); it contains a lot of biomolecules like polysaccharides, fatty acids, and triterpenoids that are known to exerting anti-oxidative, anti-inflammatory, anti-microbial and anti-tumor activities in oral cancer. In this study, we investigate AGA anti-proliferative, anti-metastatic and apoptotic activity to explore its anti-cancer activity against colon cancer cells and its underlying mechanism. METHOD: Here, in-vitro studies were performed to determine the antiproliferative activity of AGA through MTT and colony formation assays. Wound healing and transwell migration assay were used to evaluate the metastasis. Flow cytometry and protein expression were used to investigate the involved molecular mechanism by evaluating the cell cycle and apoptosis. The in-vivo anti-cancerous activity of AGA was assessed by xenograft mice model of colon cancer cells. RESULTS: We found that AGA significantly inhibited the proliferative capacity and metastasis of colon cancer cells in-vitro. In addition, AGA induced cell cycle arrest in the sub-G1 phase through upregulating p21 and downregulating CDK2, CDK6 in SW620, and CDK4 in SW480 and HT29, respectively. Annexin-v assay indicated that colon cancer cells had entered early and late apoptosis after treatment with AGA. Furthermore, a mechanistic protein expressions study revealed that AGA in p53-dependent and independent regulated the apoptosis of colon cancer by downregulating the p53 protein expression in SW620 and SW480 cells but upregulating in a dose-dependent manner in HT29 cells and increasing the expression of Bax and caspase-9 to inhibit the colon cancer cells. In vivo study, we found that AGA significantly reduced the xenograft tumor growth in NOD/SCID mice with no adverse effect on the kidney and liver. CONCLUSION: Collectively, AGA has the potential to inhibit colon cancer through inhibiting proliferation, migration, and cell cycle kinase by upregulating p21 protein expression and promoting the apoptotic protein in a p53-dependent and independent manner.

Efficacy assessment for low-level laser therapy in the treatment of androgenetic alopecia: a real-world study on 1383 patients.

Low-level laser therapy (LLLT) has been a treatment modality by many androgenetic alopecia (AGA) patients in recent years. It remained unclear as to how long the treatment regime should be maintained, and which characteristics of patients should this be recommended. A real-world study was carried out with an FDA-cleared low-level laser helmet for 1383 patients. Ordinal logistic regression analysis with propensity score matching (PSM) was used to investigate the factors related to efficacy assessment. More than 80% of users were between 18 and 40 years old. The median use times were 133 for mild AGA patients and 142 for moderate-to-severe AGA patients, which equated to 38 weeks and 40 weeks, respectively. The overall clinical effectiveness was nearly 80%. PSM analysis revealed that gender (P = 0.002), use period (P = 0.068), scalp conditions with dandruff, rash, and itchy symptoms were associated with the grading of efficacy assessment. Male users (ordinal OR: 1.35, CI: (1.01, 1.79)); use for more than 180 times or use period for 1 year (ordinal OR: 1.40, CI: (1.11, 1.96)); and those with scalp dandruff (ordinal OR: 1.34, CI: (1.01, 1.87)), rash (ordinal OR: 1.47, CI: (1.04, 2.07)), and itchy symptoms (ordinal OR: 1.51, CI: (1.12, 2.03)) had better efficacy assessments. The recommended treatment regime with low-level laser helmet was more than 1 year or 180 use times. Male patients with dandruff, rash, and itchy symptoms in scalps tended to have a better efficacy assessment.

Efficacy of botulinum toxin A injection in the treatment of androgenic alopecia: A Comparative Controlled Study.

INTRODUCTION: Scalp injection with mesotherapy (LC cell hair essence) helps in anchoring hair follicles and might have good therapeutic efficacy and lower side effects than Botox in the treatment of androgenetic alopecia (AGA). OBJECTIVE: To assess the trichoscopy and the clinical therapeutic response of LC hair essence serum injection vs. botulinum toxin (A) injection in the treatment of androgenetic alopecia. PATIENTS AND METHODS: Sixty-two AGA patients were included in the present study. Group I consisted of 31 patients who were injected with 1 ml of LC hair essence serum diluted with 0.5 ml of 0.9% normal saline once weekly for 8 weeks, and Group II involved 31 patients who were injected with 50 units of botulinum toxin A. Trichoscopic examination and photo documentation were done for every case before starting treatment (baseline) and after treatment with monthly follow-up to the patients. RESULTS: There was a significant difference between baseline trichoscopy findings and at the end of sixth month in Botox group, and the difference was highly significant in LC group; there was a statistically significant increase in the frequency of side effects (irritation and headache) among Group II compared with that of Group I. CONCLUSION: Botox can induce significant results in the treatment of AGA with mild and tolerable side effects but with high cost, while LC hair serum exhibit excellent results with fewer side effects.

Meta-analysis of photobiomodulation for the treatment of androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a condition that affects most people at some point in their life, yet few treatments are available. Use of photobiomodulation is ideal due to the safety profile and lack of serious adverse effects. Therefore, the efficacy of photobiomodulation for AGA therapy was investigated. METHODS: A meta-analysis was used to elucidate treatment efficacy. Additionally, a sub-analysis was performed to determine if the type of device used or if use of lasers versus light emitting diodes (LEDs) significantly impacted results. RESULTS: Using hair density (hairs/cm2) as a measure of efficacy, the standardized mean difference (SMD) was 1.02 (95% CI: 0.68, 1.36) in favor of treatment over control (15 studies, pooled N = 795, p < .00001). Subgroup analysis comparing comb-style devices versus helmet/hat-style devices did not reveal a significant difference (p = .08). A second subgroup analysis suggested that laser treatment was significantly more effective (p = .009) than a combination of laser/LED treatment although the combination treatment was still significantly better than control treatment. DISCUSSION: Meta-analysis results suggest that photobiomodulation could be used to effectively treat AGA. Specific device recommendations should be based on use of lasers versus LEDs and not the style (comb/hat/helmet) of the device.

The level of stress and the assessment of selected clinical parameters in patients with androgenetic alopecia.

Androgenetic alopecia is the most common type of hair loss both in male as well as female patients. It is a type of non-cicatricial hair loss. Pathophysiology of the disease remains largely unknown. It is believed that the occurrence of FPHL (female pattern hair loss) is linked with cellular insensitivity to androgens. Human hair does not only represent beauty, health and youth, but it also has a significant impact on one's self-esteem. For many patients, hair loss is a stigmatizing experience, many of them complain about a lower quality of life, anxiety or even depression. AIM: Aim of the study was to evaluate the levels of selected clinical parameters, including exposure to stress and disease progression based on the Ludwig scale, and of the applied therapies in a group of female patients with androgenetic alopecia. MATERIALS AND METHODS: A group of 106 patients with androgenetic alopecia was analyzed with respect to their age, duration of disease, disease progression based on the Ludwig scale, family history of AGA, exposure to stress (with the level of stress subjectively assessed by the patients using a score of 1 to 10), and treatment modality. Comparison of the results will be carried out with the help of the Statistica software, using the Student's t-test or its non-parametric equivalent. RESULTS: Patients reported very high levels of stress exposure: 7 and 8 on a scale of 1 to 10. The type of treatment applied (local vs. systemic) was of no significance with respect to the alleviation of stress. Disease progression was not found to correlate with the level of stress. When analyzing disease progression, using the Ludwig classification scale, most of the patients met the criteria of type I-2 (24.74%). As regards the comparison of treatment modalities in the study group, a great majority of patients was treated with topical agents in the form of scalp massage liquids (80.00%), while 17.14% of the study population underwent systemic treatment. A small percentage of patients also resorted to esthetic medicine procedures (3.81%), and 22.86% of them used dietary supplements or OTC topical agents. CONCLUSIONS: High levels of stress exposure reported by patients most probably stemmed from the symptoms of the disease itself, as the study population was quite diverse in terms of their levels of professional activity and the type of profession performed.

The Role of Early Pregnancy Maternal Selenium Levels on the Risk for Small-for-Gestational Age Newborns.

It has not yet been established, whether or not the maternal serum selenium (Se) in early pregnancy may be a risk marker of small-for-gestational age (SGA) birth weight. Selenium is important for human health and is involved in oxidative balance, a key element in the development of the placenta and fetus. This innovative study was nested in a prospective cohort of 750 women recruited in the 10-14th week of a single pregnancy, all of whom were healthy during recruitment. We examined mothers delivering SGA infants (with birth weight <10th percentile) (n = 48) and matched mothers delivering appropriate-for-gestational age (AGA) infants (between 10-90th percentile) (n = 192). We measured the maternal microelement concentrations in the serum from the 10-14th gestational week, using the inductively coupled plasma mass spectrometry (ICP-MS). The odds ratios of SGA (and 95% confidence intervals) were assessed in logistic regression. The mean maternal Se concentrations were lower in mothers in the SGA group compared to the AGA group (59.60 vs. 62.54 µg/L; p = 0.020). Women in the lowest Q1 quartile of Se (≤56.60 µg/L) have about three times higher risk of SGA compared to women in the higher quartiles (Q2 or Q4); the odds ratio of SGA was OR = 3.02 (p = 0.019) for Q1 vs. Q2 quartile. The risk profile graph confirms the results. We found that excessive pre-pregnancy BMI (body mass index) affected the estimated SGA odds ratios. Early pregnancy maternal serum selenium status can be a risk marker of SGA newborns and more research is needed in larger groups.

The promotion of hair regrowth by topical application of a Perilla frutescens extract through increased cell viability and antagonism of testosterone and dihydrotestosterone.

This study investigated the potential hair regrowth effects associated with a plant extract of Perilla frutescens, which was selected due to its putative hair regrowth activity. Extracts were prepared from dried P. frutescens suspended in distilled water, where the resultant aqueous suspension was fractionated sequentially using hexane, ethyl acetate, n-butanol, and distilled water. We observed that the n-butanol fraction resulted in the highest hair regrowth activity. The n-butanol soluble fraction of P. frutescens extract (BFPE) was further separated using AB-8 macroporous resin and silica gel chromatography to obtain rosmarinic acid (RA), which demonstrated effective hair growth regeneration potential. BFPE also showed in vivo anti-androgenic activity following the use of a hair growth assay in testosterone-sensitive male C57Bl/6NCrSlc mice. Furthermore, the effects of cell viability promotion were investigated following an in vitro analysis in primary hair follicle fibroblast cells (PHFCs) treated with RA. The results suggested that RA was the active compound in P. frutescens that triggers hair growth, and RA could be a potential therapeutic agent for the promotion of hair growth and prevention of androgenetic alopecia (AGA).

Aspartylglucosaminuria caused by a novel homozygous mutation in the AGA gene was identified by an exome-first approach in a patient from Japan.

BACKGROUND: Aspartylglucosaminuria (AGU) is an autosomal recessive lysosomal storage disorder caused by a deficiency of the lysosomal enzyme, aspartylglucosaminidase (AGA). This disorder is rare in the general population except in Finland. Since the most characteristic feature of this disorder is a progressive developmental regression, patients often show no specific symptoms in the initial stages, and thus early diagnosis is often challenging. CASE REPORT: We encountered a 16-year-old boy who began to show difficulties in his speech at the age of 6years. Due to a mild regression in his development, he gradually lost common daily abilities. His diagnosis was first obtained through exome sequencing that identified a novel homozygous mutation in the AGA gene. This result was reasonable because of parental consanguinity. Reduced enzymatic activity of AGA was then confirmed. His urine was retrospectively screened by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and a specific pattern of abnormal metabolites was identified. CONCLUSIONS: Because both exome sequencing and MALDI-TOF-MS screening are adaptable and comprehensive, future combinatory use of these methods would be useful for diagnosis of rare inborn errors of metabolism such as AGU.

Risk factors for small-for-gestational-age and preterm births among 19,269 Tanzanian newborns.

BACKGROUND: Few studies have differentiated risk factors for term-small for gestational age (SGA), preterm-appropriate for gestational age (AGA), and preterm-SGA, despite evidence of varying risk of child mortality and poor developmental outcomes. METHODS: We analyzed birth outcome data from singleton infants, who were enrolled in a large randomized, double-blind, placebo-controlled trial of neonatal vitamin A supplementation conducted in Tanzania. SGA was defined as birth weight <10th percentile for gestation age and sex using INTERGROWTH standards and preterm birth as delivery at <37 complete weeks of gestation. Risk factors for term-SGA, preterm-AGA, and preterm-SGA were examined independently using log-binomial regression. RESULTS: Among 19,269 singleton Tanzanian newborns included in this analysis, 68.3 % were term-AGA, 15.8 % term-SGA, 15.5 % preterm-AGA, and 0.3 % preterm-SGA. In multivariate analyses, significant risk factors for term-SGA included maternal age <20 years, starting antenatal care (ANC) in the 3(rd) trimester, short maternal stature, being firstborn, and male sex (all p < 0.05). Independent risk factors for preterm-AGA were maternal age <25 years, short maternal stature, firstborns, and decreased wealth (all p < 0.05). In addition, receiving ANC services in the 1(st) trimester significantly reduced the risk of preterm-AGA (p = 0.01). Significant risk factors for preterm-SGA included maternal age >30 years, being firstborn, and short maternal stature which appeared to carry a particularly strong risk (all p < 0.05). CONCLUSION: Over 30 % of newborns in this large urban and rural cohort of Tanzanian newborns were born preterm and/or SGA. Interventions to promote early attendance to ANC services, reduce unintended young pregnancies, increased maternal height, and reduce poverty may significantly decrease the burden of SGA and preterm birth in sub-Saharan Africa. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) - ACTRN12610000636055 , registered on 3(rd) August 2010.

The first competency-based higher education programme for midwives in the South Asian region--Pakistan.

Midwives in Pakistan and the South Asian region who complete a diploma program face many challenges for career growth and development. The absence of higher education in professional midwifery in the region has contributed to general non-acceptance and invisibility of midwifery. In response to the interest, Aga Khan University (AKU) developed bachelors program in midwifery based on the Global Standards for Midwifery Education developed by the International Confederation of Midwives (ICM) with the vision to equip midwives to provide full-scope practice, develop confidence to practice midwifery independently, become clinical leaders and contribute to the future of midwifery. The final curriculum had a balance of theory and clinical practice in order to develop a high level of clinical competence that would meet the ICM standards and guidelines. The two year bachelors program is currently in progress. The first cohort of 21 midwives graduated in 2014 and a second cohort was enrolled in 2015. There is a planning for a future graduate program in midwifery to prepare individuals for leadership roles in practice, teaching, maternal-child health provision and policy making through a master's degree in midwifery.

Current state of phenolic and terpenoidal dietary factors and natural products as non-coding RNA/microRNA modulators for improved cancer therapy and prevention.

The epigenetic regulation of cancer cells by small non-coding RNA molecules, the microRNAs (miRNAs), has raised particular interest in the field of oncology. These miRNAs play crucial roles concerning pathogenic properties of cancer cells and the sensitivity of cancer cells towards anticancer drugs. Certain miRNAs are responsible for an enhanced activity of drugs, while others lead to the formation of tumor resistance. In addition, miRNAs regulate survival and proliferation of cancer cells, in particular of cancer stem-like cells (CSCs), that are especially drug-resistant and, thus, cause tumor relapse in many cases. Various small molecule compounds were discovered that target miRNAs that are known to modulate tumor aggressiveness and drug resistance. This review comprises the effects of naturally occurring small molecules (phenolic compounds and terpenoids) on miRNAs involved in cancer diseases.

Employing in vitro directed molecular evolution for the selection of α-amylase variant inhibitors with activity toward cotton boll weevil enzyme.

Numerous species of insect pests attack cotton plants, out of which the cotton boll weevil (Anthonomus grandis) is the main insect in Brazil and must be controlled to avert large economic losses. Like other insect pests, A. grandis secretes a high level of α-amylases in the midgut lumen, which are required for digestion of carbohydrates. Thus, α-amylase inhibitors (α-AIs) represent a powerful tool to apply in the control of insect pests. Here, we applied DNA shuffling and phage display techniques and obtained a combinatorial library containing 108 α-AI variant forms. From this library, variants were selected exhibiting in vitro affinity for cotton boll weevil α-amylases. Twenty-six variant sequences were cloned into plant expression vectors and expressed in Arabidopsis thaliana. Transformed plant extracts were assayed in vitro to select specific and potent α-amylase inhibitors against boll weevil amylases. While the wild type inhibitors, used to create the shuffled library, did not inhibit the A. grandis α-amylases, three α-AI mutants, named α-AIC3, α-AIA11 and α-AIG4 revealed high inhibitory activities against A. grandis α-amylases in an in vitro assay. In summary, data reported here shown the potential biotechnology of new α-AI variant genes for cotton boll weevil control.