Antifungal Secondary Metabolites Produced by the Fungal Endophytes: Chemical Diversity and Potential Use in the Development of Biopesticides.

Plant diseases caused by phytopathogenic fungi can lead to huge losses in the agricultural fields and therefore remain a continuous threat to the global food security. Chemical-based fungicides contributed significantly in securing crop production. However, indiscriminate application of fungicides has led to increased chemical resistance and potential risks to human health and environment. Thus, there is an urgent need for searching for new bioactive natural products and developing them into new biopesticides. Fungal endophytes, microorganisms that reside in the fresh tissues of living plants, are regarded as untapped sources of novel natural products for exploitation in agriculture and/or medicine. Chemical examination of endophytic fungi has yielded enormous antifungal natural products with potential use in the development of biopesticides. This review summarizes a total of 132 antifungal metabolites isolated from fungal endophytes in the past two decades. The emphasis is on the unique chemical diversity of these metabolic products, together with their relevant antifungal properties. Moreover, some "star molecules," such as griseofulvin and trichothecene, as well as their synthetic derivatives that possess high potential as candidates of new natural fungicides, are also presented herein.

Cytotoxic xanthones from the plant endophytic fungus Paecilamyces sp. TE-540.

One new xanthone, chryxanthone C (1), together with four known analogues (2-5), were isolated from the cultures of Paecilamyces sp. TE-540, an endophytic fungus obtained from the leaves of Nicotiana tabacum L. The structure of 1 was elucidated by comprehensive spectral analysis including HRESIMS and 1D/2D NMR, which were confirmed by Cu Kα X-ray crystallography. Compound 1 featured an unusual dihydropyran ring fused to an aromatic ring, rather than the commonly occurring prenyl moiety. The cytotoxicity of compounds 1-5 were evaluated against five human tumour cell lines and 4 exhibited moderate to strong cytotoxicities with IC50 values ranging from 5.6 to 14.2 µM.

Transcriptome Profiling and Cytological Assessments for Identifying Regulatory Pathways Associated With Diorcinol N-Induced Autophagy in A3 Cells.

Fungal secondary metabolites serve as a rich resource for exploring lead compounds with medicinal importance. Diorcinol N (DN), a fungal secondary metabolite isolated from an endophytic fungus, Arthrinium arundinis, exhibits robust anticancer activity. However, the anticancer mechanism of DN remains unclear. In this study, we examined the growth-inhibitory effect of DN on different human cancer cell lines. We found that DN decreased the viability of A3 T-cell leukemia cells in a time- and concentration-dependent manner. Transcriptome analysis indicated that DN modulated the transcriptome of A3 cells. In total, 9,340 differentially expressed genes were found, among which 4,378 downregulated genes and 4,962 upregulated genes were mainly involved in autophagy, cell cycle, and DNA replication. Furthermore, we demonstrated that DN induced autophagy, cell cycle arrest in the G1/S phase, and downregulated the expression of autophagy- and cell cycle-related genes in A3 cells. By labeling A3 cells with acridine orange/ethidium bromide, Hoechst 33,258, and monodansylcadaverine and via transmission electron microscopy, we found that DN increased plasma membrane permeability, structural disorganization, vacuolation, and autophagosome formation. Our study provides evidence for the mechanism of anticancer activity of DN in T-cell leukemia (A3) cells and demonstrates the promise of DN as a lead or even candidate molecule for the treatment of acute lymphoblastic leukemia.

Cadinane- and drimane-type sesquiterpenoids produced by Paecilomyces sp. TE-540, an endophyte from Nicotiana tabacum L., are acetylcholinesterase inhibitors.

Sesquiterpenoids with diverse skeleton types are regarded as potential lead compounds in pharmacological and other applications. Herein, we report the discovery of two new cadinane-type sesquiterpenoids, paecilacadinol A (1) and B (2); two new drimane-type sesquiterpenoids, ustusol D (3) and ustusol E (4); and six known analogs (5-10) from the endophytic fungus Paecilomyces sp. TE-540, enriching the structural diversity of naturally occurring sesquiterpenoids. Their planar structures were determined on the basis of detailed interpretation of 1D and 2D NMR spectroscopy and HRESIMS data, while their stereochemical structures were established by X-ray crystallographic analyses for 1 and 3-8 and theoretical calculations for 2. Notably, compounds 1 and 2 represent novel examples of cadinane-type sesquiterpenoids with ether bonds formed by intramolecular dehydration. Compounds 5 and 6 showed moderate activities against acetylcholinesterase (AChE), with IC50 values of 43.02 ± 6.01 and 35.97 ± 2.12 µM, respectively. Docking analysis predicted that 5 bound well in the catalytic pocket of AChE via hydrophobic interactions with Trp84, Gly117, Ser122, and Tyr121 residues, while 6 was located with Asp72 and Ser122 residues.

A Systematic Review on Secondary Metabolites of Paecilomyces Species: Chemical Diversity and Biological Activity.

Fungi are well known for their ability to synthesize secondary metabolites, which have proven to be a rich resource for exploring lead compounds with medicinal and/or agricultural importance. The genera Aspergillus, Penicillium, and Talaromyces are the most widely studied fungal groups, from which a plethora of bioactive metabolites have been characterized. However, relatively little attention has been paid to the genus Paecilomyces, which has been reported to possess great potential for its application as a biocontrol agent. Meanwhile, a wide structural array of metabolites with attractive bioactivities has been reported from this genus. This review attempts to provide a comprehensive overview of Paecilomyces species, with emphasis on the chemical diversity and relevant biological activities of these metabolic products. Herein, a total of 148 compounds and 80 references are cited in this review, which is expected to be beneficial for the development of medicines and agrochemicals in the near future.

Glabellar Rejuvenation in Forehead Lift: Reversed Periosteum or Dermal Fat Graft to Cover Pedicled Glabellar Flap.

Forehead aging is characterized by wrinkles, loss of skin elasticity, brow ptosis, and soft-tissue atrophy. For patients with prominent rhytids and marked brow ptosis, forehead lift is still the most effective treatment with a persisting result. In order to eliminate the glabellar wrinkles, forehead lift usually requires the removal of the corrugator supercilii muscle and procerus, which can lead to glabellar flattening or depression. Instead of muscle removal, the corrugator supercilii muscle, procerus, and the underlying galea were dissected as a pedicled glabellar flap. Then reversed periosteum or dermal fat graft was used to cover the glabellar flap to restore the glabellar volume. From January 2005 to November 2014, a total of 164 coronal and 42 trichophytic forehead lifts were performed. Reversed periosteum was used to cover the glabellar flap in 191 patients while dermal fat graft was applied in 15 patients with a follow-up period ranging from 6 months to 10 years. There was no irregularity or depression in the glabellar region in the group of reversed periosteal flap. The take of dermal fat graft placed over the glabellar flap was minimal. Complications from surgical procedures occurred in 2.91% of the patients. There was 1 asymmetry, 4 patients with higher than desired frontal hairline for implantation of autologous follicular units, and 1 patient with scar hyperplasia. There was no hematoma or nerve injury, no permanent numbness, and no alopecia. The techniques are simple and effective to eliminate the glabellar wrinkles and maintain or restore the glabellar volume.

The value of serum visfatin in predicting in-stent restenosis of drug-eluting stents.

OBJECTIVE: This study aims to determine the association between serum visfatin level and in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) using drug-eluting stents (DES). METHODS: A total of 460 patients with stable coronary heart disease who underwent DES placement were included. According to the results of coronary angiography 1year after PCI, 62 patients diagnosed as ISR were enrolled into the ISR group and 398 patients without ISR were recruited into the control group. Baseline clinical data were collected, and serum visfatin level was measured using ELISA method. RESULTS: The serum visfatin levels before PCI were not different between ISR and control groups (P=0.41). However, visfatin level after PCI in the ISR group was significantly higher than in the control group [(30.2±8.6) ng/ml vs. (22.6±7.9) ng/ml, P<0.01]. In multivariate logistic regression, the independent predictors for ISR included post-procedural visfatin level (odds ratio [OR]: 2.08, 95% confidence interval [CI]: 1.19-3.65), type 2 diabetes (OR: 2.30, 95% CI: 1.10-4.79), reference vessel diameter (OR: 0.79, 95% CI: 0.63-0.98), stent length (OR: 1.52, 95% CI: 1.05-2.21) and stent diameter (OR: 0.67, 95% CI: 0.51-0.88). ROC curve analysis indicated that the area under the curve for post-procedural visfatin in predicting ISR was 0.82 (95% CI: 0.77-0.86), with the optimal cut-off value of 25.9ng/ml showing a sensitivity of 84.0% and a specificity of 69.3%. CONCLUSION: Increased serum visfatin level after DES placement is independently associated with ISR. Serum visfatin may be useful in the prediction of ISR.

Orbicularis Oculi Myocutaneous Flap for Upper Cicatricial Ectropion.

The correction of cicatricial ectropion often presents a challenge to plastic surgeons because of the difficulty obtaining tissue of similar color and texture and producing minor morbidity to donor sites. The authors present the correction of upper cicatricial ectropion by rotating the orbicularis myocutaneous flap from the same lid. From April 2008 to March 2014, 8 consecutive patients with upper cicatricial ectropion underwent transfer of orbicularis oculi myocutaneous flap. The main outcome measures included the complications, recurrence, and cosmesis. All flaps were viable with partial recurrence observed in 1 severe case. Satisfactory function and cosmesis were obtained in the evaluation of the patients during the follow-up period with a 4- to 41-month range. The redundant flap which should be excised during the blepharoplasty can be used to correct upper cicatricial ectropion. Good results can be obtained because of the well-hidden incision scar and minor donor-site morbidity.

Ptosis: An Underestimated Complication after Autologous Fat Injection into the Upper Eyelid.

BACKGROUND: Autologous fat injection into the upper eyelid is a commonly used technique in plastic surgery for volume restoration. However, ptosis, as one of the potential complications of the procedure, has been less well-discussed than other complications. OBJECTIVE: To present five cases of ptosis after autologous fat injection for the correction of sunken eyelid deformity and explore its causes. METHODS: In this retrospective, non-comparative, and interventional case series, we identified five patients with ptosis. All patients had a history of previous autologous fat injection into the upper eyelid, performed by different plastic surgeons. Preoperative, intraoperative, and postoperative photographs were taken to analyze the causes of ptosis. RESULTS: Five patients developed ptosis after autologous fat injection for upper eyelid augmentation and were referred to our group for treatment. Three of the patients had received two injections of autologous fat each. Grafted fat removal with or without levator aponeurosis advancement was required in all five cases. CONCLUSIONS: Ptosis can develop following autologous fat injection into the upper eyelid. Surgeons should be aware of this complication, which rarely manifests during the procedure itself. Techniques for performing autologous fat injection and knowledge of upper eyelid anatomy should be refined to avoid postprocedural ptosis. LEVEL OF EVIDENCE: 5 Risk.

Long-term histopathologic study of the frontalis muscle flap after frontalis suspension for severe ptosis repair.

PURPOSE: To investigate the long-term histopathologic changes of the frontalis muscle flap after frontalis muscle flap suspension for severe ptosis repair. METHODS: Eight 3-month miniature pigs were selected as the experimental animals, and self-comparison was used. The experimental side of the upper eyelid was constructed to have severe ptosis by resection of the levator aponeurosis, while the other side served as the control. Samples of the upper eyelid composite at 6 months and 12 months after ptosis repair were obtained and studied through light microscopy and transmission electron microscopy. RESULTS: The histopathologic study revealed that the frontalis muscle flap kept viable with normal muscular structure and direction 6 months and 12 months after the frontalis suspension procedure. CONCLUSIONS: The frontalis muscle flap appears to be a suitable material for frontalis suspension technique because of its feasibility and histopathologic stability.