Table 1.

Summary of NBP characteristics, extra- and intracellular ROS/RNS species, and involvement of molecules and signaling pathways in various biological samples of in vitro and in vivo NBP applications.

Device type	Gas	OES	Extracellular RONS	Intracellular RONS	Scavenger	Cell	Effect	NBP-activated pathway or molecules	NBP-reduced effects	Ref.
Jet	N2	NO•, N2∗	NO	NO	cPTIO	Osteoprogenitor cell line	Osteogenesis	ALP, COL-1	—	[36]
Jet	He	O I, NO•, N2∗, O3	—	NO	—	hPDL MSCs	Osteogenesis	ALP enzyme		[37]
Jet	N2	NO•, N2∗, O2+	—	—	—	Animal	Myogenesis	p38, MYH3, MHC, MypG, MyoD	—	[38]
Jet	He + 1%O2	•OH, O2∗, O, NO	NO	NO	Hgb	Murine-immortalized neural stem cell line C17.2 Primary rat neural stem cells (isolated from the hippocampus)	Neurogenesis	β-Tublin III, APC,	Nestin	[39]
Jet	He	•OH, •O2−	H2O2	—	—	Osteoprogenitor cells (MC3T3-E1 cell line)	Osteogenesis	ALP enzyme, ALP, OCN	—	[40]
DBD	Air	—	H2O2	H2O2, O2•-	NAC, TEMPOL	Preosteocytic cell line (MLO-A5); N1511 chondrocyte cell line	Osteogenesis & chondrogenesis	—	—	[35]
DBD	N2	NO•, N2∗,•OH	H2O2, NO	—	—	Osteoprogenitor cell line	Osteogenesis	p38, FoxO1	—	[46]
DBD	N2 and air	Excited O I	NO	O2•- (mitochondrial), H2O2 (cytosolic)	MitoTEMPO− Trolox, NAC−	Mouse neuroblastoma Neuro 2A	Neurogenesis	ERK, Trk, Ras	—	[55]
DBD	He	ROS RNS	—	ROS NO	BHA	Human adipose tissue-derived stem cells (ASCs)	Proliferation	AKT, ERK, NF-κB	—	[47]
Jet	Air	•OH, O I, N2∗	O2−, •OH, H2O2	•OH, H2O2	Mannitol, catalase and sodium pyruvate	Brain and lung cancer cell lines	Apoptosis	ERK Bak, bax, caspase,H2AX,	bcl-2	[82]
DBD	He	—	—	—	—	Cervical cancer cell line	Inhibition of migration	—	MMP9 ERK, JNK (cell migration)	[52]
Jet	He + O2	•OH, O∗, O+ (~1013/m3 ROS density)	—	Total ROS	NAC	Head and neck cancer cells	Apoptosis	JNK, p38, caspase 3	Migration invasion	[78]
Jet	He + O2	•OH, O∗, O+	—	Total ROS	NAC	Colorectal cancer cell	Apoptosis	p38, JNK, ERK, β-catenin	Cyclin D1	[79]
Jet	He + O2	O I, NO•, O+ FNS, N2∗, •OH	—	Total ROS	NAC	Thyroid cancer cell	Apoptosis	JNK, p38, caspase 3	—	[43]
Jet	Air	H2O2, Ox, OH−, •O2, NOx	H2O2, NO	H2O2, NO	NAC cPTIO	Cervical cancer cells	Apoptosis	JNK, p38	—	[80]
Jet	He	•OH, N2∗, O I	—	Total ROS, NO	NAC	Melanoma cancer cells	Apoptosis	TNF, ASK-1, JNK, p38 r-H2AX, casp3/7	—	[81]
Jet	Ar	•OH, O I, NO, N2∗	H2O2	—	NAC	Ovarian cancer cell, human primary mesothelial cells, BALB/C mice	Cancer cell migration	—	MMP9 inhibits JNK and p38	[53]
Jet	Ar	—	H2O2	—	—	Immune cell lines	—	ERK, p38, JNK HSP27 (THP-1)	—	[83]
Jet	Air	—	—	Total ROS	NAC catalase	Breast carcinoma	Apoptosis	PTEN	pAKT, STAT3 pathway, IL-6R pathway	[92]
DBD	Air	•OH, O I, N2∗	—	Total ROS	NAC	Glioblastoma and lung adenocarcinoma cell lines, BALB/c mice	Migration, growth	E-cadherin (epithelial maker)	PI3K/Akt, N-cadherin, Slug, Zeb-1	[102]
Jet	He and O2	ROS density with ~1013/m3	—	Total ROS	NAC	Head and neck cancer cell lines	Growth inhibition	—	Akt degradation	[94]