Patients with MMAF induced by novel biallelic CFAP43 mutations have good fertility outcomes after intracytoplasmic sperm injection.

As a specific type of asthenoteratozoospermia, multiple morphological abnormalities of the sperm flagella (MMAF) is characterized by composite abnormalities, including absent, short, coiled, angulation, and irregular-caliber flagella. Mutations in cilia- and flagella-associated protein 43 ( CFAP43 ) are one of the main causative factors of MMAF established to date. To identify whether there are other CFAP43 mutations related to MMAF and to determine the clinical outcomes of assisted reproductive technology for patients with MMAF harboring different mutations, we recruited and screened 30 MMAF-affected Chinese men using a 22-gene next-generation sequencing panel. After systematic analysis, seven mutations in CFAP43 , including five novel mutations and two previously reported mutations, were identified from four families and related to MMAF in an autosomal recessive pattern. Papanicolaou staining, immunofluorescence, and electronic microscopy further clarified the semen characteristics and abnormal sperm morphologies, including disorganized axonemal and peri-axonemal structures, of the CFAP43 -deficient men. The female partners of two patients were pregnant after undergoing assisted reproductive technology through intracytoplasmic sperm injection, and one of them successfully gave birth to a healthy boy. This study significantly expands the mutant spectrum of CFAP43 , and together with the available information regarding male infertility and MMAF, provides new information for the genetic diagnosis and counseling of MMAF in the future.

Effects of Danshen capsules on the pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers.

Nowadays, the Herb-drug combination is becoming increasingly popular in China. However, the possible interaction induced by their combination was examined rarely. The aim of this study was to investigate the effect of multi-dose administration of Danshen capsules on clopidogrel pharmacokinetics and pharmacodynamics in healthy volunteers. A sequential, open-label, and two-period pharmacokinetic drug interaction study was designed to compare clopidogrel pharmacokinetic parameters before and after 7 days of administration of Danshen capsules in twenty healthy male volunteers. Co-administration of multiple doses of Danshen capsules caused increases in apparent oral clearance of clopidogrel and its metabolite by 96.5% and 73.7% and apparent volume of distribution by 94.2% and 75.1%, corresponding declines in Cmax by 41.7% and 32.9%, AUC0-t by 50.3% and 41.8%, and AUC0-∞ by 49.3% and 41.5% in human volunteers, respectively. Corresponding pharmacokinetic findings, co-administration of Danshen capsules with clopidogrel decreased the antiplatelet activity compared with individual agents. The results suggested that multiple dose administration of Danshen capsules could induce cytochrome P450 (CYP) isoenzymes, thereby increasing the clearance of clopidogrel. Therefore, caution should be taken when Danshen products containing lipophilic components are used in combination with therapeutic drugs metabolized by CYP3A4.

Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

Chemotherapy is used as a primary approach in cancer treatment after routine surgery. However, chemo-resistance tends to occur when chemotherapy is used clinically, resulting in poor prognosis and recurrence. Currently, Chinese medicine may provide insight into the design of new therapies to overcome chemo-resistance. Furanodiene, as a heat-sensitive sesquiterpene, is isolated from the essential oil of Rhizoma Curcumae. Even though mounting evidence claiming that furanodiene possesses anti-cancer activities in various types of cancers, the underlying mechanisms against chemo-resistant cancer are not fully clear. Our study found that furanodiene could display anti-cancer effects by inhibiting cell viability, inducing cell cytotoxicity, and suppressing cell proliferation in doxorubicin-resistant MCF-7 breast cancer cells. Furthermore, furanodiene preferentially causes apoptosis by interfering with intrinsic/extrinsic-dependent and NF-κB-independent pathways in doxorubicin-resistant MCF-7 cells. These observations also prompt that furanodiene may be developed as a promising natural product for multidrug-resistant cancer therapy in the future.

Corrigendum: Furanodiene Induces Extrinsic and Intrinsic Apoptosis in Doxorubicin-Resistant MCF-7 Breast Cancer Cells via NF-κB-Independent Mechanism.

[This corrects the article on p. 648 in vol. 8, PMID: 28959205.].