Antitumor mechanisms and future clinical applications of the natural product triptolide.

Triptolide (TPL) is a compound sourced from Tripterygium wilfordii Hook. F., a traditional Chinese medicinal herb recognized for its impressive anti-inflammatory, anti-angiogenic, immunosuppressive, and antitumor qualities. Notwithstanding its favorable attributes, the precise mechanism through which TPL influences tumor cells remains enigmatic. Its toxicity and limited water solubility significantly impede the clinical application of TPL. We offer a comprehensive overview of recent research endeavors aimed at unraveling the antitumor mechanism of TPL in this review. Additionally, we briefly discuss current strategies to effectively manage the challenges associated with TPL in future clinical applications. By compiling this information, we aim to enhance the understanding of the underlying mechanisms involved in TPL and identify potential avenues for further advancement in antitumor therapy.

Sequential transplantation of exosomes and BMSCs pretreated with hypoxia efficiently facilitates perforator skin flap survival area in rats.

Bone marrow mesenchymal stem cells (BMSC) are promising candidates for the treatment of trans-territory perforator flap necrosis. However, the low retention and survival rate of engrafted BMSCs limit their therapeutic efficacy. Strategies either modifying BMSCs or alleviating the inflammatory environment may solve this problem. Thus, we aimed to explore the therapeutic efficacy of sequential transplantation of exosomes and hypoxia pretreated BMSCs on flap necrosis. After the perforator flap model was created, the exosomes derived from BMSCs were injected immediately into choke zone II followed by transplantation of hypoxia pretreated BMSCs on Day 2. Gross view was performed to assess the flap survival, enzyme-linked immunosorbent assay was performed to evaluate the inflammatory factor level, microvessel number was assessed and quantitative polymerase chain reaction (qPCR) was performed to assess angiogenesis. We found that exosome delivery significantly reduced inflammatory cytokines levels on Day 1 and Day 3 and promoted the engrafted BMSCs' survival on Day 7. After combining with transplantation of hypoxia pretreated BMSCs, the flap survival rate and the angiogenesis-related gene expression were significantly higher than in the other three groups; the von Willebrand factor (vWF) vascular diameter and vWF vascular count were significantly higher than in the phosphate buffered saline (PBS) group. Thus, we concluded that sequential transplantation of exosomes and BMSCs combinatorially pretreated with hypoxia further facilitated flap survival. This sequential transplantation approach provides novel insights into the clinical treatment of flap necrosis.

Efficacy and Safety of Picosecond Laser in the Treatment of Melasma: A Network Meta-analysis.

BACKGROUND: The role of lasers in the treatment of melasma and acquired hyperpigmentation disease of the skin has been suggested by clinicians. However, there is no consensus on the most efficient and safe treatment method. OBJECTIVE: To systematically evaluate the efficacy and safety of picosecond laser in the treatment of melasma. METHODS AND MATERIALS: PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese scientific journal database, and Wanfang database were searched. The data for therapeutic efficacy, melasma area and severity score, and incidence rate of adverse reactions were extracted from the included studies. RESULTS: A total of 20 studies involving 1,182 patients were included in this network meta-analysis. Combined therapy with carbamic acid and 1064-nm picosecond laser was the best measure. Melasma area and severity index score of patients after low-power fractional CO2 laser treatment was higher than that of patients after the treatment with 1064-nm picosecond laser. CONCLUSION: Aminomethyl cyclic acid combined with 1064-nm picosecond laser may have the highest effective rate after treatment. Low-power fractional CO2 laser provided the lowest melasma area and severity index score after treatment, and the incidence rate of adverse reactions after treatment, was highest when intense pulsed light was used.

Characterization of a broad-spectrum endolysin rLysJNwz and its utility against Salmonella in foods.

Salmonella is a common foodborne pathogen worldwide. The use of bacteriophage-encoded endolysins as antimicrobial agents is a promising approach for controlling pathogenic contamination. In this context, a recombinant endolysin named rLysJNwz, consisting of a single domain falling with the L-alanogyl-D-glutamate peptidase-like family, was cloned, expressed, and characterized. The yield of rLysJNwz was about 25 mg/L. Synergy between 7.5 µg/mL rLysJNwz and 0.5 mmol/L EDTA could decrease the viable counts of Salmonella NCTC 8271 by 93.28%. A synergistic effect between rLysJNwz and polymyxin B was demonstrated, exhibiting the MIC of polymyxin B decreased by twofold. Specifically, rlysJNwz had strong thermostability at temperatures (4-95 °C) and maintained high activity at pHs from 5.0 to 11.0. rlysJNwz was a metal ion-dependent peptidase, which activated by divalent metal ions such as Zn2+, Mn2+, or Ca2+. Moreover, it was also found that the synergism of rlysJNwz and EDTA had bactericidal activities against a broad range of Gram-negative bacteria, including several multidrug-resistant bacteria. The application of rLysJNwz combined with EDTA was evaluated on contaminated eggs and lettuce for 60 min, displaying more than 86.7% and 86.5% reduction of viable Salmonella, respectively. Hence, these results suggest that rLysJNwz is a potential antibacterial agent to control Salmonella, especially antibiotic-resistant pathogen contamination in the field of food safety. KEY POINTS: • rLysJNwz shows lytic activities against a broad range of Gram-negative bacteria. • Endolysin rLysJNwz is a stable metalloenzyme and has high thermostability. • rLysJNwz and 0.5 mmol/L EDTA synergistically inactivate Salmonella on eggs and lettuce.

Efficacy and Safety of Polycaprolactone in Treating Nasolabial Folds: A Prospective, Multicenter, and Randomized Controlled Trial.

Nasolabial folds (NLFs) are the most pronounced sign of facial aging. This study explored the efficacy and safety of polycaprolactone gel in treating Chinese patients with moderate-to-severe NLFs. Patients with moderate-to-severe NLF who wished to be treated by dermal fillers were recruited from three centers between July 2017 and September 2019. The randomizing ratio was 1:1 in the polycaprolactone group (polycaprolactone injection) or control group (sodium hyaluronate gel injection). The primary endpoint was the effectiveness rate of Wrinkle Severity Rating Score (WSRS) scores at 12 months after injection. The full-analysis set (FAS) and safety sets had 80 patients in the polycaprolactone group and control group, respectively. In the FAS, the effectiveness rate at 12 months in the polycaprolactone group was 88.8% compared with 23.8% in controls (P < 0.001). The improvement in WSRS sustained during 12 months in the polycaprolactone group, while gradually vanished in the control group since 3 months after surgery. The global aesthetic improvement scale (GAIS) by investigator assessments was improved, much improved, or very much improved in all patients during follow-up, while the proportion of patients with a "no change" assessment gradually increased during follow-up after 6 months in the control group. The rates of injection-related adverse event (AE) and serve injection-related AE were 8.8 versus 11.3% and 0 versus 1.3% in the polycaprolactone group and control groups, respectively. Polycaprolactone gel injection is effective and safe to treat moderate-to-severe NLFs in Chinese patients.

Research on a Partial Aperture Factor Measurement Method for the AGRI Onboard Calibration Assembly.

A partial aperture onboard calibration method can solve the onboard calibration problems of some large aperture remote sensors, which is of great significance for the development trend of increasingly large apertures in optical remote sensors. In this paper, the solar diffuser reflectance degradation monitor (SDRDM) in the onboard calibration assembly (CA) of the FengYun-4 (FY-4) advanced geostationary radiance imager (AGRI) was used as the reference radiometer. It was designed for measuring the partial aperture factor (PAF) for the AGRI onboard calibration. First, the linear response count variation relationship between the two was established under the same radiance source input. Then, according to the known bidirectional reflection distribution function (BRDF) of the solar diffuser (SD) in the CA, the relative reflectance ratio coefficient between the AGRI observation direction and the SDRDM observation direction was calculated. On this basis, the response count value of the AGRI and the SDRDM was used to realize the high-precision measurement of the PAF of the AGRI B1~B3 bands by simulating the AGRI onboard calibration measurement under the illumination of a solar simulator in the laboratory. According to the determination process of the relevant parameters of the PAF, the measurement uncertainty of the PAF was analyzed; this uncertainty was greater than 2.04% and provided an important reference for the evaluation of the onboard absolute radiometric calibration uncertainty after launch.

755-nm Alexandrite Picosecond Laser with a Diffractive Lens Array or Zoom Handpiece for Post-Inflammatory Hyperpigmentation: Two Case Reports with a Three-Year Follow-Up.

OBJECTIVE: Post-inflammatory hyperpigmentation (PIH) is a reactive hypermelanosis of various skin types, which occurs as a sequela of cutaneous inflammation or injury. Despite generally a self-limited and temporary condition, PIH is still a frustrating problem that can have significant psychosocial effects on patients, especially those with darker skin types. Laser therapy is one of the effective treatments for PIH, and various wavelength lasers and light devices have been utilized in PIH therapy. Nonetheless, data on the long-term efficacy of the 755-nm alexandrite picosecond laser are limited. METHODS: This study analyzed two cases of PIH treated with a combination of a 755-nm alexandrite picosecond laser and a diffractive lens array or zoom handpiece. Efficacy of the treatment was determined by the images of skin lesions under a fixed light source before and after each treatment, which were independently reviewed by two plastic-surgery specialists blinded to the clinical data. Improvement was classified as complete (>75%), significant (50-75%), mild (25-50%), and inefficient (<25% or no obvious change). Skin imaging analysis was carried out using the VISIA system (Canfield, USA), and dermoscopy was performed at the same time. RESULTS: After two to three courses of treatment, all cases showed significant or complete improvement, and no recurrence was observed during the three years of follow-up. CONCLUSION: A 755-nm alexandrite picosecond laser in combination with a diffractive lens array or zoom handpiece had significant and long-term efficacy for the treatment of PIH caused by trauma. However, attention should be paid to the problem of transient deepening of pigmentation during treatment.

Topical ALA-Photodynamic Therapy Combined with Acne Debridement and Meticulous Nursing for the Treatment of Moderate-Severe Acne in Adolescent Patients.

OBJECTIVE: The present study aims to explore the effect of acne debridement + meticulous nursing on 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in adolescent patients with moderate-severe acne. METHODS: A total of 60 adolescent patients with moderate-severe acne who were admitted to our plastic surgery outpatient clinic between January 2018 and January 2020 were selected as the subjects of the present retrospective study. The patients were divided into two groups: the observation group and the control group (n = 30, each). Patients in the control group were treated with standardized ALA-PDT and conventional nursing, while patients in the observation group were treated with ALA-PDT and acne debridement + meticulous nursing intervention. The treatment's therapeutic effect, adverse reaction incidence, and patient satisfaction 6 months after treatment were compared between the two groups. RESULTS: The acne debridement + meticulous nursing effectiveness was 86.7% in the observation group and 60% in the control group, and the adverse reaction incidence was 20% in the observation group and 46.7% in the control group. There existed statistically significant differences in the above-stated indicators between the two groups (p < 0.05). The difference in the visual analogue scores (VASs) for pain, which were measured immediately after the operations, between the two groups was not statistically significant (p > 0.05); however, the respective VAS differences between the two groups at 30 min and 60 min after the operation were statistically significant (p < 0.05). There was a statistically significant difference in patient satisfaction between the two groups (p < 0.05). CONCLUSION: In adolescent patients with ALA-PDT-treated moderate-severe acne, the application of acne debridement + meticulous nursing could improve the clinical treatment efficacy and patient comfort as well as reduce the adverse reaction incidence. For these reasons, the treatment method could be worth promoting in clinical practice.

Anisomycin is active in preclinical models of pediatric acute myeloid leukemia via specifically inhibiting mitochondrial respiration.

The poor outcomes in acute myeloid leukemia (AML) necessitate new treatments. In this work, we identified that anisomycin is a potential selective anti-AML candidate, particularly for those with FLT3-ITD mutation. We found that anisomycin potently inhibited proliferation and induced apoptosis in multiple AML cell lines. Anisomycin was effective in targeting progenitor cells isolated from all tested pediatric AML patients, while sparing normal counterparts. Using AML xenograft mouse models, anisomycin exhibited inhibitory effect on tumor growth throughout the whole duration without causing toxicity in mice. The combination of anisomycin with standard of care drugs is synergistic and selective in AML cell culture system and mouse model. In addition, FLT3-ITD cells were more sensitive to anisomycin than FLT3 WT cells. Mechanistic studies revealed that anisomycin acted on AML in a p38-independent manner. We found that anisomycin decreased mitochondrial respiration by disrupting complex I activity, leading to intracellular oxidative stress. AML ρ0 cells that lack of mitochondrial respiration exhibited resistance to anisomycin. Finally, we showed that mitochondrial biogenesis contributes to differential sensitivity of FLT3-ITD and FLT3 WT cells to anisomycin. Our work is the first to systematically demonstrate that anisomycin is a useful addition to the treatment armamentarium for AML. Our findings highlight the therapeutic value of mitochondrial respiration inhibition in AML patients harboring FLT3-ITD mutation.

Subcutaneous Regeneration of Engineered Cartilage: A Comparison of Cell Sheets and Chondrocyte-Scaffold Constructs in a Porcine Model.

BACKGROUND: Stable cartilage regeneration in immunocompetent large animals remains a bottleneck problem that restricts clinical application. The inflammation elicited by degradation products of scaffolds has a decisive influence on cartilage formation. Although prolonged preculture in vitro could form mature engineered cartilage and allow sufficient degradation of scaffolds, the inflammatory reaction was still observed. This study explored the feasibility of using chondrocyte sheet technology to regenerate stable cartilage in the subcutaneous environment with a pig model. METHODS: Passage 1 chondrocytes were used to form cell sheets by high-density culture. As a control, chondrocytes were seeded onto polyglycolic acid/polylactic acid scaffolds for 6 and 12 weeks' in vitro preculture, respectively. Then, they were autologously implanted subcutaneously into pigs for 2, 8, and 24 weeks. Gross view, histologic staining, and biochemical and biomechanical characteristics were evaluated. RESULTS: With prolonged culture in vitro, relatively homogeneous engineered cartilages were formed with less scaffold residue. However, the chondrocyte-polyglycolic acid/polylactic acid group still encountered severe inflammation and inferior cartilage formation at 2 and 8 weeks in vivo. The engineered cartilage with cell sheet technique exhibited a relatively more stable and mature tissue structure without obvious inflammatory response at 24 weeks in vivo, which was similar to the native auricular cartilage. CONCLUSIONS: The chondrocyte sheet technique could successfully regenerate mature and stable engineered cartilages in pig models. It is possibly an effective method of repairing cartilage defects in the clinic that uses regenerated substitutes derived from autologous cell sheets.

[Effect of the botulinum toxin type A on myocutaneous flap expansion in minipigs model].

OBJECTIVE: To investigate the histologic effect of botulinum toxin type A (Botox A) injection on myocutaneous flap expansion in minipigs model. METHODS: Seven minipigs were included in this study. Two symmetric tattoo area, 10 cm x 6 cm in size, were selected on the bilateral flank of the pigs. The Botox A was injected into one tattoo area randomly, 4 U every point, 2 cm apart, with a total dose of 96 U. The same dose of sterile normal saline (0.9%) was injected in the same fashion on the opposite side as control. 3 days after injection , two 200 ml expanders were inserted beneath the cutaneous muscle at the tattoo area. After complete expansion of 200 ml, the specimens were drawn from both groups symmetrically and were stained by means of HE and Masson. The histologic changes of myocutaneous flap were compared. Thickness of each layer in myocutaneous flap was measured in histological section. RESULTS: The thickness of cutaneous muscle, capsule, dermis were (275.74 +/- 28.93) microm, (468.03 +/- 34.28) microm, (1990.79 +/- 102.10) microm in Botox group, and (409.13 +/- 44.63) microm, (626.55 +/- 44.05) microm, (2508.44 +/- 70.71) microm in saline group, respectively, show a significant difference between the two groups (P < 0.01). The Masson stained slice showed that collagen average gray of capsule in Botox group was 185.38 +/- 9.56, which was significantly higher than that in the saline group (120.77 +/- 10.31, P < 0.01). Light microscope (HE stained sections ) showed that muscle in Botox group was significantly atrophy and cross-section of muscle fiber decreased. The muscle fiber in saline group was generally normal. It was observed through transmission electron microscope that the light and dark band of muscle cell became fuzzy and the Z line bending in Botox group. The light and dark band in saline group arranged neatly, the Z line was clear. CONCLUSIONS: Application of Botox A in myocutaneous flap expansion can make the muscle atrophy and reduce the content of collagen in capsule layer, making the myocutaneous flap thinner which is suitable for reconstruction in face and neck.

A new simple technique for making facial dimples.

In Asia, especially in China, women think a dimple is an important part of a beautiful smiling face. The dimple can make them more confident. Unfortunately, not all women have dimples. Hence, with the development of the Chinese economy, there is an increasing demand among Chinese women for the creation of dimples. Most women hope the impairment of the operation will be slight and the period of recovery short so they can go to work as quickly as possible. Some of them want to have dimples only when they smile. The authors have used a new simple technique to form 56 dimples for 36 women. During the operation, they use a syringe needle to guide a monofilament nylon suture through the dermis and the active facial muscles (usually the buccinator). A sling is formed between the skin and the buccinator muscle. The knot is tied, and the dimple is created. After the operation, patients have been satisfied with the shape of the dimples. Furthermore, hematoma and infection never occurred. As a result, on the basis of their experience, the authors conclude that this technique is simple and easy to duplicate. Moreover, this technique has many benefits. For example, with this procedure, it is easy to adjust the bulk of dimples by adjusting the tension of the knot and the amount of dermis tissue the injection needle sutures. Because no tissue is resected, there is mild postoperative swelling. Consequently, patients can return to work or other activities 2 days after the operation.